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==2019==
===The histone methyltransferase EZH2 is required for normal uterine development and function in mice===
Biol Reprod. 2019 Jun 14. pii: ioz097. doi: 10.1093/biolre/ioz097. [Epub ahead of print]
Nanjappa MK1, Mesa AM1, Medrano TI1, Jefferson WN2, DeMayo FJ2, Williams CJ2, Lydon JP3, Levin ER4,5, Cooke PS1.
Enhancer of zeste homolog 2 (EZH2) is a rate-limiting catalytic subunit of a histone methyltransferase, polycomb repressive complex, which silences gene activity through the repressive histone mark H3K27me3. EZH2 is critical for epigenetic effects of early estrogen treatment, and may be involved in uterine development and pathologies. We investigated EZH2 expression, regulation and its role in uterine development/function. Uterine epithelial EZH2 expression was associated with proliferation and was high neonatally then declined by weaning. Pre-weaning uterine EZH2 expression was comparable in wild-type and estrogen receptor 1 knockout mice, showing neonatal EZH2 expression is ESR1 independent. Epithelial EZH2 was up-regulated by 17β-estradiol (E2) and inhibited by progesterone in adult uteri from ovariectomized mice. To investigate the uterine role of EZH2, we developed a EZH2 conditional knockout (Ezh2cKO) mouse using a cre recombinase driven by the progesterone receptor (Pgr) promoter that produced Ezh2cKO mice lacking EZH2 in Pgr-expressing tissues (e.g. uterus, mammary glands). In Ezh2cKO uteri, EZH2 was deleted neonatally. These uteri had reduced H3K27me3, were larger than WT and showed adult cystic endometrial hyperplasia. Ovary-independent uterine epithelial proliferation and increased numbers of highly proliferative uterine glands were seen in adult Ezh2cKO mice. Female Ezh2cKO mice were initially subfertile, then became infertile by 9 months. Mammary gland development in Ezh2cKO mice was inhibited. In summary, uterine EZH2 expression is developmentally and hormonally regulated, and its loss causes aberrant uterine epithelial proliferation, uterine hypertrophy and cystic endometrial hyperplasia, indicating a critical role in uterine development and function.
© The Author(s) 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction.
KEYWORDS:
cell proliferation; epigenetics; mammary gland; uterus
PMID: 31201420 DOI: 10.1093/biolre/ioz097
===Livebirth after uterus transplantation from a deceased donor in a recipient with uterine infertility===
Lancet. 2019 Dec 22;392(10165):2697-2704. doi: 10.1016/S0140-6736(18)31766-5. Epub 2018 Dec 4.
Ejzenberg D1, Andraus W2, Baratelli Carelli Mendes LR2, Ducatti L2, Song A2, Tanigawa R2, Rocha-Santos V2, Macedo Arantes R2, Soares JM Jr3, Serafini PC3, Bertocco de Paiva Haddad L3, Pulcinelli Francisco R4, Carneiro D'Albuquerque LA3, Chada Baracat E3.
Author information
Abstract
BACKGROUND:
Uterus transplantation from live donors became a reality to treat infertility following a successful Swedish 2014 series, inspiring uterus transplantation centres and programmes worldwide. However, no case of livebirth via deceased donor uterus has, to our knowledge, been successfully achieved, raising doubts about its feasibility and viability, including whether the womb remains viable after prolonged ischaemia.
METHODS:
In September, 2016, a 32-year-old woman with congenital uterine absence (Mayer-Rokitansky-Küster-Hauser [MRKH] syndrome) underwent uterine transplantation in Hospital das Clínicas, University of São Paulo, Brazil, from a donor who died of subarachnoid haemorrhage. The donor was 45 years old and had three previous vaginal deliveries. The recipient had one in-vitro fertilisation cycle 4 months before transplant, which yielded eight cryopreserved blastocysts.
FINDINGS:
The recipient showed satisfactory postoperative recovery and was discharged after 8 days' observation in hospital. Immunosuppression was induced with prednisolone and thymoglobulin and continued via tacrolimus and mycophenalate mofetil (MMF), until 5 months post-transplantation, at which time azathioprine replaced MMF. First menstruation occurred 37 days post-transplantation, and regularly (every 26-32 days) thereafter. Pregnancy occurred after the first single embryo transfer 7 months post-transplantation. No blood flow velocity waveform abnormalities were detected by Doppler ultrasound of uterine arteries, fetal umbilical, or middle cerebral arteries, nor any fetal growth impairments during pregnancy. No rejection episodes occurred after transplantation or during gestation. Caesarean delivery occurred on Dec 15, 2017, near gestational week 36. The female baby weighed 2550 g at birth, appropriate for gestational age, with Apgar scores of 9 at 1 min, 10 at 5 min, and 10 at 10 min, and along with the mother remains healthy and developing normally 7 months post partum. The uterus was removed in the same surgical procedure as the livebirth and immunosuppressive therapy was suspended.
INTERPRETATION:
We describe, to our knowledge, the first case worldwide of livebirth following uterine transplantation from a deceased donor in a patient with MRKH syndrome. The results establish proof-of-concept for treating uterine infertility by transplantation from a deceased donor, opening a path to healthy pregnancy for all women with uterine factor infertility, without need of living donors or live donor surgery.
FUNDING:
Fundação de Amparo à Pesquisa do Estado de São Paulo and Hospital das Clínicas, University of São Paulo, Brazil.
Copyright © 2018 Elsevier Ltd. All rights reserved.
Comment in
Uterus transplantation from a deceased donor. [Lancet. 2019]
PMID: 30527853 DOI: 10.1016/S0140-6736(18)31766-5
==2018==
===Outcome of assisted reproduction in women with congenital uterine anomalies: a prospective observational study===
Ultrasound Obstet Gynecol. 2018 Jan;51(1):110-117. doi: 10.1002/uog.18935.
Prior M1,2, Richardson A1, Asif S1, Polanski L1, Parris-Larkin M1, Chandler J1, Fogg L1, Jassal P1, Thornton JG2, Raine-Fenning NJ1.
Abstract
OBJECTIVES:
To assess the prevalence of congenital uterine anomalies, including arcuate uterus, and their effect on reproductive outcome in subfertile women undergoing assisted reproduction.
METHODS:
Consecutive women referred for subfertility between May 2009 and November 2015 who underwent assisted reproduction were included in the study. As part of the initial assessment, each woman underwent three-dimensional transvaginal sonography. Uterine morphology was classified using the modified American Fertility Society (AFS) classification of congenital uterine anomalies proposed by Salim et al. If the external contour of the uterus was uniformly convex or had an indentation of < 10 mm, but there was a cavity indentation, it was defined as arcuate or septate. Arcuate uterus was further defined as the presence of a concave fundal indentation with a central point of indentation at an obtuse angle. Subseptate uterus was defined as the presence of a septum, not extending to the cervix, with the central point of the septum at an acute angle; if the septum extended to the internal cervical os, the uterus was defined as septate. Reproductive outcomes, including live birth, clinical pregnancy and preterm birth, were compared between women with a normal uterus and those with a congenital uterine anomaly. Subgroup analysis by type of uterine morphology and logistic regression analysis adjusted for age, body mass index, levels of anti-Müllerian hormone, antral follicle count and number and day of embryo transfer were performed.
RESULTS:
A total of 2375 women were included in the study, of whom 1943 (81.8%) had a normal uterus and 432 (18.2%) had a congenital uterine anomaly. The most common anomalies were arcuate (n = 387 (16.3%)) and subseptate (n = 16 (0.7%)) uterus. The rate of live birth was similar between women with a uterine anomaly and those with a normal uterus (35% vs 37%; P = 0.47). The rates of clinical pregnancy, mode of delivery and sex of the newborn were also similar between the two groups. Preterm birth before 37 weeks' gestation was more common in women with uterine anomalies than in controls (22% vs 14%, respectively; P = 0.03). Subgroup analysis by type of anomaly showed no difference in the incidence of live birth and clinical pregnancy for women with an arcuate uterus, but indicated worse pregnancy outcome in women with other major anomalies (P = 0.042 and 0.048, respectively).
CONCLUSIONS:
Congenital uterine anomalies as a whole, when defined using the modified AFS classification, do not affect clinical pregnancy or live-birth rates in women following assisted reproduction, but do increase the incidence of preterm birth. The presence of uterine abnormalities more severe than arcuate uterus significantly worsens all pregnancy outcomes. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
KEYWORDS:
arcuate; assisted reproduction; infertility; ultrasound; uterine anomalies
Comment in
Re: Outcome of assisted reproduction in women with congenital uterine anomalies: a prospective observational study. M. Prior, A. Richardson, S. Asif, L. Polanski, M. Parris-Larkin, J. Chandler, L. Fogg, P. Jassal, J. G. Thornton, N. J. Raine-Fenning. Ultrasound Obstet Gynecol 2018; 51: 110-117. [Ultrasound Obstet Gynecol. 2018]
PMID: 29055072 DOI: 10.1002/uog.18935
===The cell biology and molecular genetics of Müllerian duct development===
Wiley Interdiscip Rev Dev Biol. 2018 Jan 19. doi: 10.1002/wdev.310. [Epub ahead of print]
Roly ZY1, Backhouse B2, Cutting A3, Tan TY2, Sinclair AH2, Ayers KL2, Major AT1, Smith CA1.
Abstract
The Müllerian ducts are part of the embryonic urogenital system. They give rise to mature structures that serve a critical function in the transport and development of the oocyte and/or embryo. In most vertebrates, both sexes initially develop Müllerian ducts during embryogenesis, but they regress in males under the influence of testis-derived Anti-Müllerian Hormone (AMH). A number of regulatory factors have been shown to be essential for proper duct development, including Bmp and Wnt signaling molecules, together with homeodomain transcription factors such as PAX2 and LIM1. Later in development, the fate of the ducts diverges between males and females and is regulated by AMH and Wnt signaling molecules (duct regression in males) and Hox genes (duct patterning in females). Most of the genes and molecular pathways known to be involved in Müllerian duct development have been elucidated through animal models, namely, the mouse and chicken. In addition, genetic analysis of humans with reproductive tract disorders has further defined molecular mechanisms of duct formation and differentiation. However, despite our current understanding of Müllerian duct development, some questions remain to be answered at the molecular genetic level. This article is categorized under: Early Embryonic Development > Development to the Basic Body Plan.
KEYWORDS:
AMH; Lim1; Mullerian duct; PAX2; Wnt4; Wnt7a; Wnt9b; chicken embryo
PMID: 29350886 DOI: 10.1002/wdev.310
==2014==
===Lhx1 is required in Müllerian duct epithelium for uterine development===
Dev Biol. 2014 May 15;389(2):124-36. doi: 10.1016/j.ydbio.2014.01.025. Epub 2014 Feb 21.
Huang CC1, Orvis GD2, Kwan KM3, Behringer RR4.
Abstract
The female reproductive tract organs of mammals, including the oviducts, uterus, cervix and upper vagina, are derived from the Müllerian ducts, a pair of epithelial tubes that form within the mesonephroi. The Müllerian ducts form in a rostral to caudal manner, guided by and dependent on the Wolffian ducts that have already formed. Experimental embryological studies indicate that caudal elongation of the Müllerian duct towards the urogenital sinus occurs in part by proliferation at the ductal tip. The molecular mechanisms that regulate the elongation of the Müllerian duct are currently unclear. Lhx1 encodes a LIM-homeodomain transcription factor that is essential for male and female reproductive tract development. Lhx1 is expressed in both the Wolffian and Müllerian ducts. Wolffian duct-specific knockout of Lhx1 results in degeneration of the Wolffian duct and consequently the non-cell-autonomous loss of the Müllerian duct. To determine the role of Lhx1 specifically in the Müllerian duct epithelium, we performed a Müllerian duct-specific knockout study using Wnt7a-Cre mice. Loss of Lhx1 in the Müllerian duct epithelium led to a block in Müllerian duct elongation and uterine hypoplasia characterized by loss of the entire endometrium (luminal and glandular epithelium and stroma) and inner circular but not the outer longitudinal muscle layer. Time-lapse imaging and molecular analyses indicate that Lhx1 acts cell autonomously to maintain ductal progenitor cells for Müllerian duct elongation. These studies identify LHX1 as the first transcription factor that is essential in the Müllerian duct epithelial progenitor cells for female reproductive tract development. Furthermore, these genetic studies demonstrate the requirement of epithelial-mesenchymal interactions for uterine tissue compartment differentiation.
Copyright © 2014 Elsevier Inc. All rights reserved.
KEYWORDS:
Lhx1; Live imaging; Müllerian duct; Uterus; Wnt7a
PMID 24560999
===Role of morphologic characteristics of the uterine septum in the prediction and prevention of abnormal healing outcomes after hysteroscopic metroplasty===
Hum Reprod. 2014 May 16. pii: deu110. [Epub ahead of print]
Ludwin A1, Ludwin I2, Pityński K3, Banas T3, Jach R3.
Author information
Abstract
STUDY QUESTION:
Can morphologic measurements (width, length and surface area) of the uterine septum predict healing-dependent abnormal anatomic results [ARs; residual septum (RS) and intrauterine adhesions in other locations (IUA-OLs)] after complete hysteroscopic metroplasty (HM)?
SUMMARY ANSWER:
Significant predictors of ARs are the septal width and, to a lesser extent, septal surface area.
WHAT IS KNOWN ALREADY:
Anatomic results after hysteroscopic metroplasty have very large variation. A RS >1 cm and IUA-OLs can aggravate reproductive outcomes, resulting in the need for reoperation. New criteria for diagnosing a uterine septum according to the European Society of Human Reproduction and Embryology (ESHRE) and European Society for Gynaecological Endoscopy (ESGE) have been suggested (ESHRE-ESGE criteria). Autocross-linked hyaluronic acid gel (autocross-linked polysaccharide) has an antiadhesive effect.
STUDY DESIGN, SIZE, DURATION:
A prospective, observational cohort study was performed with 96 women consecutively enrolled between 2007 and 2012.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
Women who had uterine septum and previous miscarriage or infertility presented for evaluation at a university hospital, private hospital or private medical center were included. Preoperative septal width, length and surface area were determined with three-dimensional sonohysterography. Women were treated by hysteroscopy in a standardized manner with three- or four-dimensional transrectal ultrasound guidance (complete resection). Patients received either no adhesion barrier (49 patients) or adhesion barrier with autocross-linked polysaccharide (47 patients). Anatomic results were assessed with three-dimensional sonohysterography and second-look hysteroscopy. Healing-dependent ARs were reported using both American Society of Reproductive Medicine (ASRM) criterion of RS length >1 cm (ASRM>1 cm criterion) and ESHRE-ESGE criteria. Univariate and multivariate logistic regression were used to identify predictors of RS, IUA-OLs and ARs.
MAIN RESULTS AND ROLE OF CHANCE:
In patients who had no adhesion barrier, ARs were diagnosed in 11 of 49 patients (23%) using the ASRM > 1 cm criterion and in 20 of 49 patients (41%) using the ESHRE-ESGE criteria for RS [odds ratio (OR)ESHRE-ESGE:ASRM, 2.4, P = 0.05]. In the patients who had autocross-linked polysaccharide, ARsASRM > 1 cm were diagnosed in 2 of 47 patients (4%) and ARsESHRE-ESGE in 4 of 47 patients (9%). RSESHRE-ESGE was diagnosed significantly more often than RSASRM > 1 cm 19 of 96 (20%) versus 5 of 96 (5%) in all patients (ORESHRE-ESGE:ASRM > 1 cm = 4.5, P < 0.01). In patients who had no adhesion barrier, logistic regression with ASRM > 1 cm and ESHRE-ESGE criteria showed that the width and surface area were predictors of ARs. Models adjusted by patient group confirmed the significance of width as a predictor of ARsASRM > 1 cm [OR for width, 3.5 (P < 0.01); OR for group, 0.22 (P < 0.01)], width as a predictor of ARsESHRE-ESGE [OR for width, 2.2 (P < 0.01); OR for group, 0.26 (P < 0.01)] and surface area as a predictor of ARsASRM > 1 cm [OR for surface area, 1.5 (P < 0.01)]; OR for group, 0.32 (P < 0.01). In patients who had autocross-linked polysaccharide, these predictors were not significant. Receiver-operating characteristic curves showed cutoff values for ARsASRM > 1 cm (septal width, 3.42 cm; septal surface area, 4.68cm2) and ARsESHRE-ESGE (septal width, 3.42 cm; septal surface area, 3.51cm2).
LIMITATIONS AND REASONS FOR CAUTION:
Patients were enrolled in the adhesion barrier group in a time-dependent, consecutive and non-randomized manner.
WIDER IMPLICATIONS OF THE FINDINGS:
A wide septum and large surface area may be indications for adhesion barrier. The use of autocross-linked polysaccharide reduces the risk of ARs. The ESHRE-ESGE criteria may cause greater frequency of recognition of RS than the ASRM > 1 cm criterion, which could result in more frequent reoperations with use of the ESHRE-ESGE criteria, possibly without any significant effect on reproductive performance.
STUDY FUNDING/COMPETING INTERESTS:
This work was supported by Jagiellonian University (grant no. K/ZDS/003821). The authors have no competing interest to declare.
© The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.
KEYWORDS:
autocross-linked hyaluronic acid gel; classification system; intrauterine adhesions; septate uterus; three-dimensional sonohysterography
PMID 24838703
==2013==
===The ESHRE/ESGE consensus on the classification of female genital tract congenital anomalies===
Hum Reprod. 2013 Aug;28(8):2032-44. doi: 10.1093/humrep/det098. Epub 2013 Jun 14.
Grimbizis GF1, Gordts S, Di Spiezio Sardo A, Brucker S, De Angelis C, Gergolet M, Li TC, Tanos V, Brölmann H, Gianaroli L, Campo R.
Abstract
STUDY QUESTION:
What classification system is more suitable for the accurate, clear, simple and related to the clinical management categorization of female genital anomalies?
SUMMARY ANSWER:
The new ESHRE/ESGE classification system of female genital anomalies is presented.
WHAT IS KNOWN ALREADY:
Congenital malformations of the female genital tract are common miscellaneous deviations from normal anatomy with health and reproductive consequences. Until now, three systems have been proposed for their categorization but all of them are associated with serious limitations.
STUDY DESIGN, SIZE AND DURATION:
The European Society of Human Reproduction and Embryology (ESHRE) and the European Society for Gynaecological Endoscopy (ESGE) have established a common Working Group, under the name CONUTA (CONgenital UTerine Anomalies), with the goal of developing a new updated classification system. A scientific committee (SC) has been appointed to run the project, looking also for consensus within the scientists working in the field.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
The new system is designed and developed based on (i) scientific research through critical review of current proposals and preparation of an initial proposal for discussion between the experts, (ii) consensus measurement among the experts through the use of the DELPHI procedure and (iii) consensus development by the SC, taking into account the results of the DELPHI procedure and the comments of the experts. Almost 90 participants took part in the process of development of the ESHRE/ESGE classification system, contributing with their structured answers and comments.
MAIN RESULTS AND THE ROLE OF CHANCE:
The ESHRE/ESGE classification system is based on anatomy. Anomalies are classified into the following main classes, expressing uterine anatomical deviations deriving from the same embryological origin: U0, normal uterus; U1, dysmorphic uterus; U2, septate uterus; U3, bicorporeal uterus; U4, hemi-uterus; U5, aplastic uterus; U6, for still unclassified cases. Main classes have been divided into sub-classes expressing anatomical varieties with clinical significance. Cervical and vaginal anomalies are classified independently into sub-classes having clinical significance.
LIMITATIONS, REASONS FOR CAUTION:
The ESHRE/ESGE classification of female genital anomalies seems to fulfill the expectations and the needs of the experts in the field, but its clinical value needs to be proved in everyday practice.
WIDER IMPLICATIONS OF THE FINDINGS:
The ESHRE/ESGE classification system of female genital anomalies could be used as a starting point for the development of guidelines for their diagnosis and treatment.
STUDY FUNDING/COMPETING INTEREST(S):
None.
KEYWORDS:
anatomy; classification system; female tract
Comment in
Are the ESHRE/ESGE criteria of female genital anomalies for diagnosis of septate uterus appropriate? [Hum Reprod. 2014]
Reply: are the ESHRE/ESGE criteria of female genital anomalies for diagnosis of septate uterus appropriate? [Hum Reprod. 2014]
PMID 23771171 [PubMed - indexed for MEDLINE] PMCID: PMC3712660
==2012==
===Pregnancies in women with uterine malformation, treated obstruction of hemivagina and ipsilateral renal agenesis===
Arch Gynecol Obstet. 2012 Dec 18. [Epub ahead of print]
Heinonen PK.
Source
Department of Obstetrics and Gynecology, Tampere University Hospital Medical School, University of Tampere, 33014, Tampere, Finland, pentti.heinonen@uta.fi.
Abstract
PURPOSE:
The aim of this study was to evaluate the outcome of pregnancies in women who had uterine malformation and surgically treated obstructed hemivagina with ipsilateral renal agenesis.
METHODS:
The study group comprised 21 women with malformed uterus (12 didelphic, 6 septate and 3 bicornuate uterus). All of them had a history of surgical excision of the longitudinal vaginal septum caused obstructed hemivagina and ipsilateral renal agenesis. All pregnancies and possible surgical interventions were evaluated during the follow-up period (median 13.2 years).
RESULTS:
Thirteen out of 21 women attempting pregnancy conceived. They produced 22 pregnancies, 17 (77 %) were contralateral to the treated obstructed hemivagina and unilateral renal agenesis. The median interval between surgical treatment of obstructed hemivagina and the first pregnancy was 10.5 years. Twenty (91 %) pregnancies ended in delivery of a living infant. Preeclampsia (14 %), preterm delivery (36 %), high frequency (38 %) of fetal breech presentation and the cesarean section rate (67 %) were found.
CONCLUSIONS:
Accurate diagnosis and appropriate surgery to open an obstructed hemivagina in adolescence assure fertility. Preterm birth is associated with malformed uterus and unilateral renal agenesis may predispose to preeclampsia.
PMID 23247278
http://humrep.oxfordjournals.org/content/29/7/1420.full
http://creativecommons.org/licenses/by-nc/3.0/
===Congenital developmental defects of derivates of müllerian ducts===
Endocr Dev. 2012;22:251-70. Epub 2012 Jul 25.
Hořejší J.
Source
Department of Obstetrics and Gynecology, Charles University Prague, 2nd Medical Faculty and Teaching Hospital Praha-Motol, Prague, Czech Republic. jan.horejsi@lfmotol.cuni.cz
Abstract
Congenital developmental defects of Müllerian derivates, understandable with the knowledge of embryological development of Wolffian and Müllerian ducts, are defects of canalisation (= gynatresias), defects in fusing, combined defects and uterovaginal agenesis. Gynatresias should be suspected in the newborn, but distinguished in puberty, on the basis of menstrual blood retention, as hymeneal atresia (haematocolpos), aplasia partis distalis vaginae (haematocolpos partialis), transversal vagina septum and aplasia of vagina and uterine cervix (isolated haematometra). Particular operations are described. Defects in the fusing of Müllerian ducts from the point of view of surgery could be single-coated or double-coated. Incomplete reduplication with unilateral renal aplasia syndrome could present as hemihaematocolpos, hemihaematometra and haematometra in rudimental horn. For diagnosis of these disorders menstrual blood retention is necessary. Surgical treatment in the first two types includes resection of the common wall and haematometra in rudimental horn needs metroplasty or hemihysterectomy. Congenital absence of uterus and vagina (Rokitanski Küster) appears in genetically, endocrinologically and psychosexually normal females. Diagnosis is based on clinical examination and ultrasonography. Initial examination should be nonsurgical (dilatation method). All surgical corrections create a place for the future vagina and reach its epithelization. Different procedures are criticised. The author recommends and describes Vecchietti's laparoscopic surgery.
Copyright © 2012 S. Karger AG, Basel.
PMID 22846534
==2011==
===A high-resolution molecular atlas of the fetal mouse lower urogenital tract===
Dev Dyn. 2011 Oct;240(10):2364-77. doi: 10.1002/dvdy.22730. Epub 2011 Sep 8.
Abler LL, Keil KP, Mehta V, Joshi PS, Schmitz CT, Vezina CM.
Source
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison Wisconsin, USA.
Abstract
Epithelial-stromal interactions in the lower urogenital tract (LUT) are integral to prostatic and seminal vesicle development in males, vaginal and uterine development in females, and urethral development in both sexes. Gene expression profiling of isolated LUT stroma and epithelium has unraveled mechanisms of LUT development, but such studies are confounded by heterogeneous and ill-defined cell sub-populations contained within each tissue compartment. We used in situ hybridization to synthesize a high-resolution molecular atlas of 17-day post-coitus fetal mouse LUT. We identified mRNAs that mark selective cell populations of the seminal vesicle, ejaculatory duct, prostate, urethra, and vagina, subdividing these tissues into 16 stromal and 8 epithelial sub-compartments. These results provide a powerful tool for mapping LUT gene expression patterns and also reveal previously uncharacterized sub-compartments that may play mechanistic roles in LUT development of which we were previously unaware.
Copyright © 2011 Wiley-Liss, Inc.
PMID 21905163
===Normal and abnormal epithelial differentiation in the female reproductive tract===
Differentiation. 2011 Oct;82(3):117-26. doi: 10.1016/j.diff.2011.04.008. Epub 2011 May 25.
Kurita T.
Source
Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. t-kurita@northwestern.edu
Abstract
In mammals, the female reproductive tract (FRT) develops from a pair of paramesonephric or Müllerian ducts (MDs), which arise from coelomic epithelial cells of mesodermal origin. During development, the MDs undergo a dynamic morphogenetic transformation from simple tubes consisting of homogeneous epithelium and surrounding mesenchyme into several distinct organs namely the oviduct, uterus, cervix and vagina. Following the formation of anatomically distinctive organs, the uniform MD epithelium (MDE) differentiates into diverse epithelial cell types with unique morphology and functions in each organ. Classic tissue recombination studies, in which the epithelium and mesenchyme isolated from the newborn mouse FRT were recombined, have established that the organ specific epithelial cell fate of MDE is dictated by the underlying mesenchyme. The tissue recombination studies have also demonstrated that there is a narrow developmental window for the epithelial cell fate determination in MD-derived organs. Accordingly, the developmental plasticity of epithelial cells is mostly lost in mature FRT. If the signaling that controls epithelial differentiation is disrupted at the critical developmental stage, the cell fate of MD-derived epithelial tissues will be permanently altered and can result in epithelial lesions in adult life. A disruption of signaling that maintains epithelial cell fate can also cause epithelial lesions in the FRT. In this review, the pathogenesis of cervical/vaginal adenoses and uterine squamous metaplasia is discussed as examples of such incidences.
Copyright © 2011. Published by Elsevier B.V.
PMID 21612855
===The prevalence of congenital uterine anomalies in unselected and high-risk populations: a systematic review===
Hum Reprod Update. 2011 Nov-Dec;17(6):761-71. Epub 2011 Jun 24.
Chan YY, Jayaprakasan K, Zamora J, Thornton JG, Raine-Fenning N, Coomarasamy A.
Source
Department of Obstetrics and Gynaecology, Nottingham University Hospitals NHS Trust, Queen's Medical Centre Campus, Derby Road, Nottingham NG7 2UH, UK. yeeyin@gmail.com
Abstract
BACKGROUND:
The prevalence of congenital uterine anomalies in high-risk women is unclear, as several different diagnostic approaches have been applied to different groups of patients. This review aims to evaluate the prevalence of such anomalies in unselected populations and in women with infertility, including those undergoing IVF treatment, women with a history of miscarriage, women with infertility and recurrent miscarriage combined, and women with a history of preterm delivery.
METHODS:
Searches of MEDLINE, EMBASE, Web of Science and the Cochrane register were performed. Study selection and data extraction were conducted independently by two reviewers. Studies were grouped into those that used 'optimal' and 'suboptimal' tests for uterine anomalies. Meta-analyses were performed to establish the prevalence of uterine anomalies and their subtypes within the various populations.
RESULTS:
We identified 94 observational studies comprising 89 861 women. The prevalence of uterine anomalies diagnosed by optimal tests was 5.5% [95% confidence interval (CI), 3.5-8.5] in the unselected population, 8.0% (95% CI, 5.3-12) in infertile women, 13.3% (95% CI, 8.9-20.0) in those with a history of miscarriage and 24.5% (95% CI, 18.3-32.8) in those with miscarriage and infertility. Arcuate uterus is most common in the unselected population (3.9%; 95% CI, 2.1-7.1), and its prevalence is not increased in high-risk groups. In contrast, septate uterus is the most common anomaly in high-risk populations.
CONCLUSIONS:
Women with a history of miscarriage or miscarriage and infertility have higher prevalence of congenital uterine anomalies compared with the unselected population.
PMID 21705770
==2009==
===Müllerian duct anomalies and mimics in children and adolescents: correlative intraoperative assessment with clinical imaging===
Radiographics. 2009 Jul-Aug;29(4):1085-103.
Junqueira BL, Allen LM, Spitzer RF, Lucco KL, Babyn PS, Doria AS.
Department of Diagnostic Imaging, Hospital for Sick Children, 555 University Ave, Toronto, ON, Canada M5G 1X8.
Abstract
Müllerian duct anomalies (MDAs) are congenital entities that result from nondevelopment, defective vertical or lateral fusion, or resorption failure of the müllerian (paramesonephric) ducts. MDAs are common, although the majority are asymptomatic, and have been classified by the American Society of Reproductive Medicine according to clinical manifestations, prognosis, and treatment. Accurate diagnosis of an MDA is essential, since the management approach varies depending on the type of malformation. In females, when a müllerian duct becomes obstructed, the patient may present with an abdominal mass and dysmenorrhea. If the patient is not treated in a timely fashion, the consequences can be severe, extending even to infertility. When an MDA is suspected, ultrasonography (US) should be performed initially to delineate any abnormalities in the genital tract. However, US cannot help identify the type of MDA. In contrast, magnetic resonance imaging is a valuable technique for noninvasive evaluation of the female pelvic anatomy and accurate MDA classification. If obstruction is present, surgical correction of the MDA may be required, and further counseling of the patient with regard to reproductive possibilities becomes important. Supplemental material available at http://radiographics.rsnajnls.org/cgi/content/full/29/4/1085/DC1.
Copyright RSNA, 2009
PMID: 19605658
http://www.ncbi.nlm.nih.gov/pubmed/16272225
http://radiographics.rsna.org/content/29/4/1085.long
--[[User:S8600021|Mark Hill]] 16:18, 14 December 2010 (EST) Good illustrated review of uterine abnormalities.
==2007==
===Physiology of upward transport in the human female genital tract===
Zervomanolakis I, Ott HW, Hadziomerovic D, Mattle V, Seeber BE, Virgolini I, Heute D, Kissler S, Leyendecker G, Wildt L.
Ann N Y Acad Sci. 2007 Apr;1101:1-20. Epub 2007 Apr 7.
PMID: 17416925 [PubMed - indexed for MEDLINE]
The uterus and fallopian tubes represent a functionally united peristaltic pump under the endocrine control of ipsilateral ovary. We have examined this function by using hysterosalpingoscintigraphy (HSS), recording of intrauterine pressure, electrohysterography, and Doppler sonography of the fallopian tubes. An uptake of labeled particles into the uterus was observed during the follicular and luteal phases of the cycle after application into the vagina. Transport into the oviducts, however, could only be demonstrated during the follicular phase. Furthermore, the predominant transport was into the tube ipsilateral to the ovary containing the dominant follicle. The pregnancy rate following spontaneous intercourse or insemination was higher in those women in whom ipsilateral transport could be demonstrated. The amount of material transported to the ipsilateral tube was increased after oxytocin administration, as demonstrated by radionuclide imaging and by Doppler sonography following instillation of ultrasound contrast medium. An increase in the basal tone and amplitude of contractions was observed after oxytocin administration. These results support the idea that the uterus and fallopian tubes act as a peristaltic pump, which increases transport of sperm into the oviduct ipsilateral to the ovary bearing the dominant follicle. Oxytocin appears to play a critical role in this peristaltic pump. A failure of the peristaltic mechanism is possibly responsible for infertility. We propose the term tubal transport disorder (TTD) as a nosological entity. Results from HSS could be a useful adjunct for choosing treatment modalities in patients with patent fallopian tubes suffering from infertility. These patients may be better served with in vitro fertilization (IVF).
===Role of the oviduct in sperm capacitation===
Rodriguez-Martinez H.
Theriogenology. 2007 Sep 1;68 Suppl 1:S138-46. Epub 2007 Apr 23. Review.
PMID: 17452049 [PubMed - indexed for MEDLINE]
Following insemination of spermatozoa pre-ovulation, the mammalian oviduct ensures, by the formation of a functional sperm reservoir (SR), that suitable (low) numbers of viable and potentially fertile spermatozoa are available for fertilization at the ampullary isthmic junction (AIJ). As ovulation approaches, a proportion of the SR-stored spermatozoa is continuously distributed towards the AIJ and individually activated leading to step-wise capacitation and the attainment of hyperactivated motility. This paper reviews in vivo changes in the intra-luminal milieu of the oviduct of pigs and cows, in particular the SR and the AIJ which relate to the modulation of sperm capacitation around spontaneous ovulation. In vivo, most viable spermatozoa in the pre-ovulatory SR are uncapacitated. Capacitation rates significantly increase after ovulation, apparently not massively but concurrent with the individual, continuous sperm dislocation from the SR. Bicarbonate, whose levels differ between the SR and the AIJ, appears as the common primary effector of the membrane destabilizing changes that encompasses the first stages of capacitation. Sperm activation can be delayed or even reversed by co-incubation with membrane proteins of the tubal lining, isthmic fluid or specific tubal glycosaminoglycans, such as hyaluronan. Although the pattern of response to in vitro induction of sperm activation - capacitation in particular - is similar for all spermatozoa, the capacity and speed of the response is very individual. Such diversity in responsiveness among spermatozoa insures full sperm viability before ovulation and the presence of spermatozoa at different stages of capacitation at the AIJ, thus maximizing the chances of normal fertilization.
==2006==
===Sperm transport in the female reproductive tract===
Suarez SS, Pacey AA.
Hum Reprod Update. 2006 Jan-Feb;12(1):23-37. Epub 2005 Nov 4. Review.
PMID 16272225
==2005==
===Microscopical survey of the development and differentiation of the epithelium of the uterine tube and uterus in the human fetus===
Ital J Anat Embryol. 2005;110(2 Suppl 1):231-7.
Barberini F, Correr S, Makabe S.
Source
Laboratory of Electron Microscopy Pietro M. Motta, Department of Anatomy, University of Rome La Sapienza, Rome, Italy. fabrizio.barberini@uniroma1.it
Abstract
The development and differentiation of the coelomic epithelium lining the paramesonephric ducts in human fetus, that gives rise to the female genital organs, have been ultrastructurally examined. The epithelium appeared pseudostratified, consisting of basal, microvillous and ciliated cells. In younger fetuses (12th gestational week) ciliogenic elements could be detected mainly on the developing tubal fimbriae, but most of the cells showed microvilli and often single cilia. In the subsequent phases of development, morphodynamics of cell renewal were documented by aspects of apoptosis. Fully ciliated cells were numerous on the fimbriae and at the utero-tubal junction, but not in the uterus; however, these were less abundant than those showing microvillous. In older fetuses (31st gestational week) microapocrine secretion by microvillous cells, in the form of droplets contacting cilia, could be observed. In the same fetuses the ectocervix was covered by a mature squamous epithelium, made up of polygonal flat desquamating cells, showing labyrinthine surface microplicae. Our observations demonstrated that ciliation in the human female genital organs, like that of other systems, is neither simultaneous nor uniform, and ciliated cells are gathered preferentially in strategic sites, to mediate germ cell migration and blastocyst implantation in adult life. These ultrastructural data seem to indicate that the female genital tract epithelium, at least in its general features, is sketched since fetal life, and cell morphodynamics, including microvillous and ciliated cell differentiation, as well as the secretory activity, are the morphological expression of the complex molecular mechanisms, involved in developmental biology and reproductive physiology.
PMID 16101043
==2001==
===Developmental biology of uterine glands===
Biol Reprod. 2001 Nov;65(5):1311-23.
Gray CA1, Bartol FF, Tarleton BJ, Wiley AA, Johnson GA, Bazer FW, Spencer TE.
Abstract
All mammalian uteri contain endometrial glands that synthesize or transport and secrete substances essential for survival and development of the conceptus (embryo/fetus and associated extraembryonic membranes). In rodents, uterine secretory products of the endometrial glands are unequivocally required for establishment of uterine receptivity and conceptus implantation. Analyses of the ovine uterine gland knockout model support a primary role for endometrial glands and, by default, their secretions in peri-implantation conceptus survival and development. Uterine adenogenesis is the process whereby endometrial glands develop. In humans, this process begins in the fetus, continues postnatally, and is completed during puberty. In contrast, endometrial adenogenesis is primarily a postnatal event in sheep, pigs, and rodents. Typically, endometrial adenogenesis involves differentiation and budding of glandular epithelium from luminal epithelium, followed by invagination and extensive tubular coiling and branching morphogenesis throughout the uterine stroma to the myometrium. This process requires site-specific alterations in cell proliferation and extracellular matrix (ECM) remodeling as well as paracrine cell-cell and cell-ECM interactions that support the actions of specific hormones and growth factors. Studies of uterine development in neonatal ungulates implicate prolactin, estradiol-17 beta, and their receptors in mechanisms regulating endometrial adenogenesis. These same hormones appear to regulate endometrial gland morphogenesis in menstruating primates and humans during reconstruction of the functionalis from the basalis endometrium after menses. In sheep and pigs, extensive endometrial gland hyperplasia and hypertrophy occur during gestation, presumably to provide increasing histotrophic support for conceptus growth and development. In the rabbit, sheep, and pig, a servomechanism is proposed to regulate endometrial gland development and differentiated function during pregnancy that involves sequential actions of ovarian steroid hormones, pregnancy recognition signals, and lactogenic hormones from the pituitary or placenta. That disruption of uterine development during critical organizational periods can alter the functional capacity and embryotrophic potential of the adult uterus reinforces the importance of understanding the developmental biology of uterine glands. Unexplained high rates of peri-implantation embryonic loss in humans and livestock may reflect defects in endometrial gland morphogenesis due to genetic errors, epigenetic influences of endocrine disruptors, and pathological lesions.
PMID 11673245
===Formation of Fallopian tubal fluid: role of a neglected epithelium===
Leese HJ, Tay JI, Reischl J, Downing SJ.
Reproduction. 2001 Mar;121(3):339-46. Review.
PMID: 11226059
==1999==
===The fetal development of the human uterine cervix from the 12th to the 31st postmenstrual week as revealed by scanning electron microscopy. Anatomical and clinical correlations===
Ital J Anat Embryol. 1999 Jul-Sep;104(3):77-87.
Barberini F, Makabe S, Correr S, Motta PM.
Source
Department of Human Anatomy, University of Rome La Sapienza, Italy.
Abstract
To clarify the differentiation of the human uterine cervix, fetuses of the 12th, 15th, 18th, 20th, 21st, 22nd, and 31st postmenstrual week were studied by Scanning Electron Microscopy. At the 12th week the endocervical epithelium consisted of microvillous cells, often showing single cilia and anlages of tubular glands. At the 15th week the cervical canal was entirely formed and its surface cells appeared columnar. At the 18th week these cells were replaced by flat or slightly raised cells, provided with thin microplicae. At the 20th week the endocervical epithelium appeared pseudostratified with higher, apically-convex and shorter basal cells; glands developed in form of tubular invaginations of the luminal epithelium. At the 21st week in the lower part of the endocervix polymorphic, globose cells with short and stubby microvilli and others elongated, having short microplicae, were observed. These latter likely corresponded to the so-called columnar cells undergoing squamous metaplasia. Among microvillous and/or metaplastic cells, a number of apoptotic cells, as globose elements with a ruffled and invaginated surface, were also noted. At the 22nd week evident plicae palmatae were found, covered by microvillous secreting cells. These showed smooth bulged apices releasing droplets by a "micro-apocrine" mechanism. These features increased at the 31st week, when many droplets were noted also around the mouth of the cervical glands. Only at this phase of development fully ciliated cells were found often contacting secretory material. Mature squamous exfoliating cells with complex microplicae covered an hypertrophied portio vaginalis. The squamous cells extended toward a squamo-columnar junction in form of flat, tongue-like projections. Their tips consisted of immature squamous metaplastic cells, which were endocervical columnar progressively becoming elongated elements, exhibiting short microvilli. The above features are rather similar to those occurring during the adult reproductive age. Therefore, it might be hypothesized that, during pregnancy, a common gestational hormonal background may induce somewhat similar morpho-dynamic processes in the cells and tissues of the fetal reproductive tract mimicking what occurs in the adult female.
PMID 10575820
==1994==
===An ultrastructural study of epithelium differentiation in the human fetal fallopian tube===
Acta Anat (Basel). 1994;151(4):207-19.
Barberini F, Makabe S, Correr S, Luzi A, Motta PM.
Source
Department of Anatomy, University of Rome La Sapienza, Italy.
Abstract
The epithelial structure of the developing human fetal Fallopian tube has been studied systematically by parallel light, transmission and scanning electron microscopy. The specimens for this study were collected from spontaneous abortions at the 14th, 18th, 20th and 22nd weeks and from cases of intrauterine fetal death at the 24th and 31st weeks (hydrocephalus). The epithelium lining the wall of the female genital ducts was pseudostratified in a columnar fashion. It consisted of differentiating ciliated and microvillous cells and some degenerating elements. Microvillous cells-by far the most abundant in the early phases of tubal development-often showed a solitary cilium. Ciliated elements, though always less numerous than microvillous cells, were more densely concentrated on the developing fimbriae and at the uterotubal junction than in the ampulla. On the mucosal surface of the same regions, rounded intercellular holes delimited many crypts, from which ciliated elements sometimes sprouted. Notable aspects of cell proliferation and ciliogenesis were commonly observed and are likely to be related to circulating estrogens. These ultrastructural data indicate that the typical pattern of the adult oviduct is already sketched in fetal life. Furthermore, a strategic gathering of cilia was noted primarily at the sites of the developing oviduct, which will serve to mediate the passage of sperm and/or ova and promote fertilization in adult life.
PMID 7740916
----
New aspects of gamete transport, fertilization, and embryonic development in the oviduct gained by means of live cell imaging.
Kölle S, Reese S, Kummer W.
Theriogenology. 2010 Apr 1;73(6):786-95. Epub 2010 Jan 18. Review.
PMID: 20080295 [PubMed - indexed for MEDLINE]
Related citations
2.
Ciliary transport, gamete interaction, and effects of the early embryo in the oviduct: ex vivo analyses using a new digital videomicroscopic system in the cow.
Kölle S, Dubielzig S, Reese S, Wehrend A, König P, Kummer W.
Biol Reprod. 2009 Aug;81(2):267-74. Epub 2009 Mar 18.
PMID: 19299315 [PubMed - indexed for MEDLINE]
Related citations
3.
[Role of the female environment in sperm capacitation]
Patrat C, Serres C.
Gynecol Obstet Fertil. 2009 Jun;37(6):536-9. Epub 2009 May 20. French.
PMID: 19467904 [PubMed - indexed for MEDLINE]
Related citations
4.
Contributions to myometrium study in uterine-tubal junction.
Neamţu MC, Neamţu RL, Avramescu ET, Vrabete M, Călina LM, Mîndrilă I.
Rom J Morphol Embryol. 2009;50(4):675-81.
PMID: 19942965 [PubMed - indexed for MEDLINE]Free Article
Related citations
5.
Fertilization and early embryonic development in the porcine fallopian tube.
Brüssow KP, Rátky J, Rodriguez-Martinez H.
Reprod Domest Anim. 2008 Jul;43 Suppl 2:245-51. Review.
PMID: 18638131 [PubMed - indexed for MEDLINE]
Related citations
6.
Regulation of sperm storage and movement in the mammalian oviduct.
Suarez SS.
Int J Dev Biol. 2008;52(5-6):455-62. Review.
PMID: 18649258 [PubMed - indexed for MEDLINE]Free Article
Related citations
9.
Sperm binding glycoprotein is differentially present surrounding the lumen of isthmus and ampulla of the pig's oviduct.
Pérez FA, Roma SM, Cabada MO, Marini PE.
Anat Embryol (Berl). 2006 Nov;211(6):619-24. Epub 2006 Sep 1.
PMID: 16947066 [PubMed - indexed for MEDLINE]
Related citations
10.
Relationship between the fertile period and sperm transport in the bitch.
England GC, Burgess CM, Freeman SL, Smith SC, Pacey AA.
Theriogenology. 2006 Oct;66(6-7):1410-8. Epub 2006 Mar 15. Review.
PMID: 16540160 [PubMed - indexed for MEDLINE]
Related citations
11.
Gamete/embryo - oviduct interactions: implications on in vitro culture.
Lee KF, Yeung WS.
Hum Fertil (Camb). 2006 Sep;9(3):137-43. Review.
PMID: 17008265 [PubMed - indexed for MEDLINE]
Related citations
12.
Oviductal motile response to penile cervical buffeting.
Shafik A, Shafik I, El Sibai O, Shafik AA.
Arch Gynecol Obstet. 2006 Jan;273(4):216-20. Epub 2005 Sep 16.
PMID: 16167158 [PubMed - indexed for MEDLINE]
Related citations
----
http://www.ncbi.nlm.nih.gov/pubmed/7004702
PIP: The anatomy and physiology of the human fallopian tube are described and discussed; then, these facts are correlated with clinical considerations as they relate to tubal factor infertility. Anatomically the human oviduct is a tubular, seromuscular organ attached distally to the ovary and proximally to the lateral aspect of the uterine fundus. Its length averages 11-12 cm. The oviduct can be divided into 4 main segments: 1) the infundibulum, whose terminal end contains the tubal ostium; 2) the ampullary region; 3) the isthmic portion; and 4) the intramural or interstitial portion, which is contained in the wall of the uterus. 4 electron micrographs illustrate these areas. Also discussed in this reveiw are the vascular analtomy, the lymphatics, and neuroanatomy of the fallopian tubes. Physiologic functions discussed in this article include the role of the fallopian tube in sperm transport, its part in sperm maintenance and capacitation, and the tube's function in ovum transport, fertilization, and embryo transport. Clinically, the role of the myosalpinx is undetermined, although it may affect tubal motility and ovum transport. The dense adrenergic innervation of the oviductal isthmus, along with the myosalpinx, suggests that innervation may be required for sphincter-like activity, although again no evidence exists for innervation being required in normal reproduction. The mucosa provides nutrients which may or may not be essential to normal reproduction, and its cilia seems uncritical in gamete transport and embryogenesis. Evidence shows that the uterotubal junction and the ampullary-isthmic junction are not necessary for conception (based on success rates of implantation procedures). Reversal of fimbriectomy is the most difficult and up to 1-cm of ampulla may be removed and resected and still maintain fertility.


Effects of transmaternal exposure to genistein in Hatano high- and low-avoidance rats.
Effects of transmaternal exposure to genistein in Hatano high- and low-avoidance rats.
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http://www.rbej.com/content/7/1/132
http://www.rbej.com/content/7/1/132


==Vagina Development==
==Cervix==
 
Slides 22 and 23 histology of the cervix
* The cervix is lined by stratified squamous epithelium AND mucinous columnar epithelium
* endocervix by columnar epithelium
* ectocervix by squamous
* relevance to the transformation zone.


[[Vagina Development]]


* The development of the human vagina. BULMER D. J Anat. 1957 Oct;91(4):490-509. No abstract available. [http://www.ncbi.nlm.nih.gov/pubmed/13475148 PMID: 13475148] | [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1244904/ PMCID: 1244904]


* New concepts on the development of the vagina. Shapiro E, Huang H, Wu XR. Adv Exp Med Biol. 2004;545:173-85. Review. No abstract available. [http://www.ncbi.nlm.nih.gov/pubmed/15086027 PMID: 15086027]


* Revisiting old vaginal topics: conversion of the Müllerian vagina and origin of the "sinus" vagina. Cai Y. Int J Dev Biol. 2009;53(7):925-34. Review. [http://www.ncbi.nlm.nih.gov/pubmed/19598112 PMID: 19598112] | [http://www.ijdb.ehu.es/web/paper.php?doi=10.1387/ijdb.082846yc IJDB]


:"Vaginal development has been a longstanding controversy, which hampers studies on vaginal diseases as well as cervical and uterine diseases. Most concerns center on: why is the vaginal epithelium different from the uterine epithelium; and where does the vagina originate from? It is commonly held that the rodent vagina has a dual origin: the cranial part is derived from the Mullerian duct (Mullerian vagina) and the caudal part derived from the urogenital sinus (sinus vagina). This concept was deduced from morphological observations. However, it cannot explain the difference between the Mullerian vagina and the uterus. Moreover, accumulating new data from genetic and molecular studies contradicts the urogenital sinus origin of the sinus vagina. The present review summarizes previous morphological observations and new findings from genetic and molecular studies, and addresses molecular mechanisms underlying the origin and organogenesis of the vagina in rodents. It provides evidence to show that the whole vagina is derived the Mullerian duct. BMP4 reshapes the intermediate mesoderm-derived Mullerian duct into the vaginal primordium. The latter thus exhibits different features from the uterus, including the stratified squamous epithelium and insensitivity to anti-Mullerian hormone. The sinus vagina is formed by extrinsic BMP4-mediated caudal extension of the Mullerian duct. The present review thus shows how a century of controversy over the origin and organogenesis of the vagina has been resolved. This new understanding will provide additional insight into genetic diseases and tumors of the female reproductive tract."




* Fetal development of the female external urinary sphincter complex: an anatomical and histological study. Sebe P, Fritsch H, Oswald J, Schwentner C, Lunacek A, Bartsch G, Radmayr C. J Urol. 2005 May;173(5):1738-42; discussion 1742. PMID: 15821572





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Cite this page: Hill, M.A. (2024, March 28) Embryology Uterus Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Uterus_Development

2019

The histone methyltransferase EZH2 is required for normal uterine development and function in mice

Biol Reprod. 2019 Jun 14. pii: ioz097. doi: 10.1093/biolre/ioz097. [Epub ahead of print]

Nanjappa MK1, Mesa AM1, Medrano TI1, Jefferson WN2, DeMayo FJ2, Williams CJ2, Lydon JP3, Levin ER4,5, Cooke PS1.

Enhancer of zeste homolog 2 (EZH2) is a rate-limiting catalytic subunit of a histone methyltransferase, polycomb repressive complex, which silences gene activity through the repressive histone mark H3K27me3. EZH2 is critical for epigenetic effects of early estrogen treatment, and may be involved in uterine development and pathologies. We investigated EZH2 expression, regulation and its role in uterine development/function. Uterine epithelial EZH2 expression was associated with proliferation and was high neonatally then declined by weaning. Pre-weaning uterine EZH2 expression was comparable in wild-type and estrogen receptor 1 knockout mice, showing neonatal EZH2 expression is ESR1 independent. Epithelial EZH2 was up-regulated by 17β-estradiol (E2) and inhibited by progesterone in adult uteri from ovariectomized mice. To investigate the uterine role of EZH2, we developed a EZH2 conditional knockout (Ezh2cKO) mouse using a cre recombinase driven by the progesterone receptor (Pgr) promoter that produced Ezh2cKO mice lacking EZH2 in Pgr-expressing tissues (e.g. uterus, mammary glands). In Ezh2cKO uteri, EZH2 was deleted neonatally. These uteri had reduced H3K27me3, were larger than WT and showed adult cystic endometrial hyperplasia. Ovary-independent uterine epithelial proliferation and increased numbers of highly proliferative uterine glands were seen in adult Ezh2cKO mice. Female Ezh2cKO mice were initially subfertile, then became infertile by 9 months. Mammary gland development in Ezh2cKO mice was inhibited. In summary, uterine EZH2 expression is developmentally and hormonally regulated, and its loss causes aberrant uterine epithelial proliferation, uterine hypertrophy and cystic endometrial hyperplasia, indicating a critical role in uterine development and function. © The Author(s) 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction.

KEYWORDS: cell proliferation; epigenetics; mammary gland; uterus PMID: 31201420 DOI: 10.1093/biolre/ioz097

Livebirth after uterus transplantation from a deceased donor in a recipient with uterine infertility

Lancet. 2019 Dec 22;392(10165):2697-2704. doi: 10.1016/S0140-6736(18)31766-5. Epub 2018 Dec 4.

Ejzenberg D1, Andraus W2, Baratelli Carelli Mendes LR2, Ducatti L2, Song A2, Tanigawa R2, Rocha-Santos V2, Macedo Arantes R2, Soares JM Jr3, Serafini PC3, Bertocco de Paiva Haddad L3, Pulcinelli Francisco R4, Carneiro D'Albuquerque LA3, Chada Baracat E3. Author information Abstract BACKGROUND: Uterus transplantation from live donors became a reality to treat infertility following a successful Swedish 2014 series, inspiring uterus transplantation centres and programmes worldwide. However, no case of livebirth via deceased donor uterus has, to our knowledge, been successfully achieved, raising doubts about its feasibility and viability, including whether the womb remains viable after prolonged ischaemia. METHODS: In September, 2016, a 32-year-old woman with congenital uterine absence (Mayer-Rokitansky-Küster-Hauser [MRKH] syndrome) underwent uterine transplantation in Hospital das Clínicas, University of São Paulo, Brazil, from a donor who died of subarachnoid haemorrhage. The donor was 45 years old and had three previous vaginal deliveries. The recipient had one in-vitro fertilisation cycle 4 months before transplant, which yielded eight cryopreserved blastocysts. FINDINGS: The recipient showed satisfactory postoperative recovery and was discharged after 8 days' observation in hospital. Immunosuppression was induced with prednisolone and thymoglobulin and continued via tacrolimus and mycophenalate mofetil (MMF), until 5 months post-transplantation, at which time azathioprine replaced MMF. First menstruation occurred 37 days post-transplantation, and regularly (every 26-32 days) thereafter. Pregnancy occurred after the first single embryo transfer 7 months post-transplantation. No blood flow velocity waveform abnormalities were detected by Doppler ultrasound of uterine arteries, fetal umbilical, or middle cerebral arteries, nor any fetal growth impairments during pregnancy. No rejection episodes occurred after transplantation or during gestation. Caesarean delivery occurred on Dec 15, 2017, near gestational week 36. The female baby weighed 2550 g at birth, appropriate for gestational age, with Apgar scores of 9 at 1 min, 10 at 5 min, and 10 at 10 min, and along with the mother remains healthy and developing normally 7 months post partum. The uterus was removed in the same surgical procedure as the livebirth and immunosuppressive therapy was suspended. INTERPRETATION: We describe, to our knowledge, the first case worldwide of livebirth following uterine transplantation from a deceased donor in a patient with MRKH syndrome. The results establish proof-of-concept for treating uterine infertility by transplantation from a deceased donor, opening a path to healthy pregnancy for all women with uterine factor infertility, without need of living donors or live donor surgery. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo and Hospital das Clínicas, University of São Paulo, Brazil. Copyright © 2018 Elsevier Ltd. All rights reserved. Comment in Uterus transplantation from a deceased donor. [Lancet. 2019] PMID: 30527853 DOI: 10.1016/S0140-6736(18)31766-5

2018

Outcome of assisted reproduction in women with congenital uterine anomalies: a prospective observational study

Ultrasound Obstet Gynecol. 2018 Jan;51(1):110-117. doi: 10.1002/uog.18935.

Prior M1,2, Richardson A1, Asif S1, Polanski L1, Parris-Larkin M1, Chandler J1, Fogg L1, Jassal P1, Thornton JG2, Raine-Fenning NJ1.

Abstract

OBJECTIVES: To assess the prevalence of congenital uterine anomalies, including arcuate uterus, and their effect on reproductive outcome in subfertile women undergoing assisted reproduction. METHODS: Consecutive women referred for subfertility between May 2009 and November 2015 who underwent assisted reproduction were included in the study. As part of the initial assessment, each woman underwent three-dimensional transvaginal sonography. Uterine morphology was classified using the modified American Fertility Society (AFS) classification of congenital uterine anomalies proposed by Salim et al. If the external contour of the uterus was uniformly convex or had an indentation of < 10 mm, but there was a cavity indentation, it was defined as arcuate or septate. Arcuate uterus was further defined as the presence of a concave fundal indentation with a central point of indentation at an obtuse angle. Subseptate uterus was defined as the presence of a septum, not extending to the cervix, with the central point of the septum at an acute angle; if the septum extended to the internal cervical os, the uterus was defined as septate. Reproductive outcomes, including live birth, clinical pregnancy and preterm birth, were compared between women with a normal uterus and those with a congenital uterine anomaly. Subgroup analysis by type of uterine morphology and logistic regression analysis adjusted for age, body mass index, levels of anti-Müllerian hormone, antral follicle count and number and day of embryo transfer were performed. RESULTS: A total of 2375 women were included in the study, of whom 1943 (81.8%) had a normal uterus and 432 (18.2%) had a congenital uterine anomaly. The most common anomalies were arcuate (n = 387 (16.3%)) and subseptate (n = 16 (0.7%)) uterus. The rate of live birth was similar between women with a uterine anomaly and those with a normal uterus (35% vs 37%; P = 0.47). The rates of clinical pregnancy, mode of delivery and sex of the newborn were also similar between the two groups. Preterm birth before 37 weeks' gestation was more common in women with uterine anomalies than in controls (22% vs 14%, respectively; P = 0.03). Subgroup analysis by type of anomaly showed no difference in the incidence of live birth and clinical pregnancy for women with an arcuate uterus, but indicated worse pregnancy outcome in women with other major anomalies (P = 0.042 and 0.048, respectively). CONCLUSIONS: Congenital uterine anomalies as a whole, when defined using the modified AFS classification, do not affect clinical pregnancy or live-birth rates in women following assisted reproduction, but do increase the incidence of preterm birth. The presence of uterine abnormalities more severe than arcuate uterus significantly worsens all pregnancy outcomes. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. KEYWORDS: arcuate; assisted reproduction; infertility; ultrasound; uterine anomalies Comment in Re: Outcome of assisted reproduction in women with congenital uterine anomalies: a prospective observational study. M. Prior, A. Richardson, S. Asif, L. Polanski, M. Parris-Larkin, J. Chandler, L. Fogg, P. Jassal, J. G. Thornton, N. J. Raine-Fenning. Ultrasound Obstet Gynecol 2018; 51: 110-117. [Ultrasound Obstet Gynecol. 2018] PMID: 29055072 DOI: 10.1002/uog.18935

The cell biology and molecular genetics of Müllerian duct development

Wiley Interdiscip Rev Dev Biol. 2018 Jan 19. doi: 10.1002/wdev.310. [Epub ahead of print]

Roly ZY1, Backhouse B2, Cutting A3, Tan TY2, Sinclair AH2, Ayers KL2, Major AT1, Smith CA1.

Abstract

The Müllerian ducts are part of the embryonic urogenital system. They give rise to mature structures that serve a critical function in the transport and development of the oocyte and/or embryo. In most vertebrates, both sexes initially develop Müllerian ducts during embryogenesis, but they regress in males under the influence of testis-derived Anti-Müllerian Hormone (AMH). A number of regulatory factors have been shown to be essential for proper duct development, including Bmp and Wnt signaling molecules, together with homeodomain transcription factors such as PAX2 and LIM1. Later in development, the fate of the ducts diverges between males and females and is regulated by AMH and Wnt signaling molecules (duct regression in males) and Hox genes (duct patterning in females). Most of the genes and molecular pathways known to be involved in Müllerian duct development have been elucidated through animal models, namely, the mouse and chicken. In addition, genetic analysis of humans with reproductive tract disorders has further defined molecular mechanisms of duct formation and differentiation. However, despite our current understanding of Müllerian duct development, some questions remain to be answered at the molecular genetic level. This article is categorized under: Early Embryonic Development > Development to the Basic Body Plan. KEYWORDS: AMH; Lim1; Mullerian duct; PAX2; Wnt4; Wnt7a; Wnt9b; chicken embryo PMID: 29350886 DOI: 10.1002/wdev.310

2014

Lhx1 is required in Müllerian duct epithelium for uterine development

Dev Biol. 2014 May 15;389(2):124-36. doi: 10.1016/j.ydbio.2014.01.025. Epub 2014 Feb 21.

Huang CC1, Orvis GD2, Kwan KM3, Behringer RR4.

Abstract

The female reproductive tract organs of mammals, including the oviducts, uterus, cervix and upper vagina, are derived from the Müllerian ducts, a pair of epithelial tubes that form within the mesonephroi. The Müllerian ducts form in a rostral to caudal manner, guided by and dependent on the Wolffian ducts that have already formed. Experimental embryological studies indicate that caudal elongation of the Müllerian duct towards the urogenital sinus occurs in part by proliferation at the ductal tip. The molecular mechanisms that regulate the elongation of the Müllerian duct are currently unclear. Lhx1 encodes a LIM-homeodomain transcription factor that is essential for male and female reproductive tract development. Lhx1 is expressed in both the Wolffian and Müllerian ducts. Wolffian duct-specific knockout of Lhx1 results in degeneration of the Wolffian duct and consequently the non-cell-autonomous loss of the Müllerian duct. To determine the role of Lhx1 specifically in the Müllerian duct epithelium, we performed a Müllerian duct-specific knockout study using Wnt7a-Cre mice. Loss of Lhx1 in the Müllerian duct epithelium led to a block in Müllerian duct elongation and uterine hypoplasia characterized by loss of the entire endometrium (luminal and glandular epithelium and stroma) and inner circular but not the outer longitudinal muscle layer. Time-lapse imaging and molecular analyses indicate that Lhx1 acts cell autonomously to maintain ductal progenitor cells for Müllerian duct elongation. These studies identify LHX1 as the first transcription factor that is essential in the Müllerian duct epithelial progenitor cells for female reproductive tract development. Furthermore, these genetic studies demonstrate the requirement of epithelial-mesenchymal interactions for uterine tissue compartment differentiation. Copyright © 2014 Elsevier Inc. All rights reserved. KEYWORDS: Lhx1; Live imaging; Müllerian duct; Uterus; Wnt7a PMID 24560999

Role of morphologic characteristics of the uterine septum in the prediction and prevention of abnormal healing outcomes after hysteroscopic metroplasty

Hum Reprod. 2014 May 16. pii: deu110. [Epub ahead of print]

Ludwin A1, Ludwin I2, Pityński K3, Banas T3, Jach R3. Author information

Abstract STUDY QUESTION: Can morphologic measurements (width, length and surface area) of the uterine septum predict healing-dependent abnormal anatomic results [ARs; residual septum (RS) and intrauterine adhesions in other locations (IUA-OLs)] after complete hysteroscopic metroplasty (HM)? SUMMARY ANSWER: Significant predictors of ARs are the septal width and, to a lesser extent, septal surface area. WHAT IS KNOWN ALREADY: Anatomic results after hysteroscopic metroplasty have very large variation. A RS >1 cm and IUA-OLs can aggravate reproductive outcomes, resulting in the need for reoperation. New criteria for diagnosing a uterine septum according to the European Society of Human Reproduction and Embryology (ESHRE) and European Society for Gynaecological Endoscopy (ESGE) have been suggested (ESHRE-ESGE criteria). Autocross-linked hyaluronic acid gel (autocross-linked polysaccharide) has an antiadhesive effect. STUDY DESIGN, SIZE, DURATION: A prospective, observational cohort study was performed with 96 women consecutively enrolled between 2007 and 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women who had uterine septum and previous miscarriage or infertility presented for evaluation at a university hospital, private hospital or private medical center were included. Preoperative septal width, length and surface area were determined with three-dimensional sonohysterography. Women were treated by hysteroscopy in a standardized manner with three- or four-dimensional transrectal ultrasound guidance (complete resection). Patients received either no adhesion barrier (49 patients) or adhesion barrier with autocross-linked polysaccharide (47 patients). Anatomic results were assessed with three-dimensional sonohysterography and second-look hysteroscopy. Healing-dependent ARs were reported using both American Society of Reproductive Medicine (ASRM) criterion of RS length >1 cm (ASRM>1 cm criterion) and ESHRE-ESGE criteria. Univariate and multivariate logistic regression were used to identify predictors of RS, IUA-OLs and ARs. MAIN RESULTS AND ROLE OF CHANCE: In patients who had no adhesion barrier, ARs were diagnosed in 11 of 49 patients (23%) using the ASRM > 1 cm criterion and in 20 of 49 patients (41%) using the ESHRE-ESGE criteria for RS [odds ratio (OR)ESHRE-ESGE:ASRM, 2.4, P = 0.05]. In the patients who had autocross-linked polysaccharide, ARsASRM > 1 cm were diagnosed in 2 of 47 patients (4%) and ARsESHRE-ESGE in 4 of 47 patients (9%). RSESHRE-ESGE was diagnosed significantly more often than RSASRM > 1 cm 19 of 96 (20%) versus 5 of 96 (5%) in all patients (ORESHRE-ESGE:ASRM > 1 cm = 4.5, P < 0.01). In patients who had no adhesion barrier, logistic regression with ASRM > 1 cm and ESHRE-ESGE criteria showed that the width and surface area were predictors of ARs. Models adjusted by patient group confirmed the significance of width as a predictor of ARsASRM > 1 cm [OR for width, 3.5 (P < 0.01); OR for group, 0.22 (P < 0.01)], width as a predictor of ARsESHRE-ESGE [OR for width, 2.2 (P < 0.01); OR for group, 0.26 (P < 0.01)] and surface area as a predictor of ARsASRM > 1 cm [OR for surface area, 1.5 (P < 0.01)]; OR for group, 0.32 (P < 0.01). In patients who had autocross-linked polysaccharide, these predictors were not significant. Receiver-operating characteristic curves showed cutoff values for ARsASRM > 1 cm (septal width, 3.42 cm; septal surface area, 4.68cm2) and ARsESHRE-ESGE (septal width, 3.42 cm; septal surface area, 3.51cm2). LIMITATIONS AND REASONS FOR CAUTION: Patients were enrolled in the adhesion barrier group in a time-dependent, consecutive and non-randomized manner. WIDER IMPLICATIONS OF THE FINDINGS: A wide septum and large surface area may be indications for adhesion barrier. The use of autocross-linked polysaccharide reduces the risk of ARs. The ESHRE-ESGE criteria may cause greater frequency of recognition of RS than the ASRM > 1 cm criterion, which could result in more frequent reoperations with use of the ESHRE-ESGE criteria, possibly without any significant effect on reproductive performance. STUDY FUNDING/COMPETING INTERESTS: This work was supported by Jagiellonian University (grant no. K/ZDS/003821). The authors have no competing interest to declare. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. KEYWORDS: autocross-linked hyaluronic acid gel; classification system; intrauterine adhesions; septate uterus; three-dimensional sonohysterography


PMID 24838703

2013

The ESHRE/ESGE consensus on the classification of female genital tract congenital anomalies

Hum Reprod. 2013 Aug;28(8):2032-44. doi: 10.1093/humrep/det098. Epub 2013 Jun 14.

Grimbizis GF1, Gordts S, Di Spiezio Sardo A, Brucker S, De Angelis C, Gergolet M, Li TC, Tanos V, Brölmann H, Gianaroli L, Campo R.

Abstract

STUDY QUESTION: What classification system is more suitable for the accurate, clear, simple and related to the clinical management categorization of female genital anomalies? SUMMARY ANSWER: The new ESHRE/ESGE classification system of female genital anomalies is presented. WHAT IS KNOWN ALREADY: Congenital malformations of the female genital tract are common miscellaneous deviations from normal anatomy with health and reproductive consequences. Until now, three systems have been proposed for their categorization but all of them are associated with serious limitations. STUDY DESIGN, SIZE AND DURATION: The European Society of Human Reproduction and Embryology (ESHRE) and the European Society for Gynaecological Endoscopy (ESGE) have established a common Working Group, under the name CONUTA (CONgenital UTerine Anomalies), with the goal of developing a new updated classification system. A scientific committee (SC) has been appointed to run the project, looking also for consensus within the scientists working in the field. PARTICIPANTS/MATERIALS, SETTING, METHODS: The new system is designed and developed based on (i) scientific research through critical review of current proposals and preparation of an initial proposal for discussion between the experts, (ii) consensus measurement among the experts through the use of the DELPHI procedure and (iii) consensus development by the SC, taking into account the results of the DELPHI procedure and the comments of the experts. Almost 90 participants took part in the process of development of the ESHRE/ESGE classification system, contributing with their structured answers and comments. MAIN RESULTS AND THE ROLE OF CHANCE: The ESHRE/ESGE classification system is based on anatomy. Anomalies are classified into the following main classes, expressing uterine anatomical deviations deriving from the same embryological origin: U0, normal uterus; U1, dysmorphic uterus; U2, septate uterus; U3, bicorporeal uterus; U4, hemi-uterus; U5, aplastic uterus; U6, for still unclassified cases. Main classes have been divided into sub-classes expressing anatomical varieties with clinical significance. Cervical and vaginal anomalies are classified independently into sub-classes having clinical significance. LIMITATIONS, REASONS FOR CAUTION: The ESHRE/ESGE classification of female genital anomalies seems to fulfill the expectations and the needs of the experts in the field, but its clinical value needs to be proved in everyday practice. WIDER IMPLICATIONS OF THE FINDINGS: The ESHRE/ESGE classification system of female genital anomalies could be used as a starting point for the development of guidelines for their diagnosis and treatment. STUDY FUNDING/COMPETING INTEREST(S): None. KEYWORDS: anatomy; classification system; female tract Comment in Are the ESHRE/ESGE criteria of female genital anomalies for diagnosis of septate uterus appropriate? [Hum Reprod. 2014] Reply: are the ESHRE/ESGE criteria of female genital anomalies for diagnosis of septate uterus appropriate? [Hum Reprod. 2014]

PMID 23771171 [PubMed - indexed for MEDLINE] PMCID: PMC3712660


2012

Pregnancies in women with uterine malformation, treated obstruction of hemivagina and ipsilateral renal agenesis

Arch Gynecol Obstet. 2012 Dec 18. [Epub ahead of print]

Heinonen PK. Source Department of Obstetrics and Gynecology, Tampere University Hospital Medical School, University of Tampere, 33014, Tampere, Finland, pentti.heinonen@uta.fi.

Abstract

PURPOSE: The aim of this study was to evaluate the outcome of pregnancies in women who had uterine malformation and surgically treated obstructed hemivagina with ipsilateral renal agenesis. METHODS: The study group comprised 21 women with malformed uterus (12 didelphic, 6 septate and 3 bicornuate uterus). All of them had a history of surgical excision of the longitudinal vaginal septum caused obstructed hemivagina and ipsilateral renal agenesis. All pregnancies and possible surgical interventions were evaluated during the follow-up period (median 13.2 years). RESULTS: Thirteen out of 21 women attempting pregnancy conceived. They produced 22 pregnancies, 17 (77 %) were contralateral to the treated obstructed hemivagina and unilateral renal agenesis. The median interval between surgical treatment of obstructed hemivagina and the first pregnancy was 10.5 years. Twenty (91 %) pregnancies ended in delivery of a living infant. Preeclampsia (14 %), preterm delivery (36 %), high frequency (38 %) of fetal breech presentation and the cesarean section rate (67 %) were found. CONCLUSIONS: Accurate diagnosis and appropriate surgery to open an obstructed hemivagina in adolescence assure fertility. Preterm birth is associated with malformed uterus and unilateral renal agenesis may predispose to preeclampsia.

PMID 23247278

http://humrep.oxfordjournals.org/content/29/7/1420.full

http://creativecommons.org/licenses/by-nc/3.0/

Congenital developmental defects of derivates of müllerian ducts

Endocr Dev. 2012;22:251-70. Epub 2012 Jul 25.

Hořejší J. Source Department of Obstetrics and Gynecology, Charles University Prague, 2nd Medical Faculty and Teaching Hospital Praha-Motol, Prague, Czech Republic. jan.horejsi@lfmotol.cuni.cz

Abstract

Congenital developmental defects of Müllerian derivates, understandable with the knowledge of embryological development of Wolffian and Müllerian ducts, are defects of canalisation (= gynatresias), defects in fusing, combined defects and uterovaginal agenesis. Gynatresias should be suspected in the newborn, but distinguished in puberty, on the basis of menstrual blood retention, as hymeneal atresia (haematocolpos), aplasia partis distalis vaginae (haematocolpos partialis), transversal vagina septum and aplasia of vagina and uterine cervix (isolated haematometra). Particular operations are described. Defects in the fusing of Müllerian ducts from the point of view of surgery could be single-coated or double-coated. Incomplete reduplication with unilateral renal aplasia syndrome could present as hemihaematocolpos, hemihaematometra and haematometra in rudimental horn. For diagnosis of these disorders menstrual blood retention is necessary. Surgical treatment in the first two types includes resection of the common wall and haematometra in rudimental horn needs metroplasty or hemihysterectomy. Congenital absence of uterus and vagina (Rokitanski Küster) appears in genetically, endocrinologically and psychosexually normal females. Diagnosis is based on clinical examination and ultrasonography. Initial examination should be nonsurgical (dilatation method). All surgical corrections create a place for the future vagina and reach its epithelization. Different procedures are criticised. The author recommends and describes Vecchietti's laparoscopic surgery. Copyright © 2012 S. Karger AG, Basel.

PMID 22846534

2011

A high-resolution molecular atlas of the fetal mouse lower urogenital tract

Dev Dyn. 2011 Oct;240(10):2364-77. doi: 10.1002/dvdy.22730. Epub 2011 Sep 8.

Abler LL, Keil KP, Mehta V, Joshi PS, Schmitz CT, Vezina CM. Source Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison Wisconsin, USA.

Abstract

Epithelial-stromal interactions in the lower urogenital tract (LUT) are integral to prostatic and seminal vesicle development in males, vaginal and uterine development in females, and urethral development in both sexes. Gene expression profiling of isolated LUT stroma and epithelium has unraveled mechanisms of LUT development, but such studies are confounded by heterogeneous and ill-defined cell sub-populations contained within each tissue compartment. We used in situ hybridization to synthesize a high-resolution molecular atlas of 17-day post-coitus fetal mouse LUT. We identified mRNAs that mark selective cell populations of the seminal vesicle, ejaculatory duct, prostate, urethra, and vagina, subdividing these tissues into 16 stromal and 8 epithelial sub-compartments. These results provide a powerful tool for mapping LUT gene expression patterns and also reveal previously uncharacterized sub-compartments that may play mechanistic roles in LUT development of which we were previously unaware. Copyright © 2011 Wiley-Liss, Inc.

PMID 21905163

Normal and abnormal epithelial differentiation in the female reproductive tract

Differentiation. 2011 Oct;82(3):117-26. doi: 10.1016/j.diff.2011.04.008. Epub 2011 May 25.

Kurita T. Source Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. t-kurita@northwestern.edu Abstract In mammals, the female reproductive tract (FRT) develops from a pair of paramesonephric or Müllerian ducts (MDs), which arise from coelomic epithelial cells of mesodermal origin. During development, the MDs undergo a dynamic morphogenetic transformation from simple tubes consisting of homogeneous epithelium and surrounding mesenchyme into several distinct organs namely the oviduct, uterus, cervix and vagina. Following the formation of anatomically distinctive organs, the uniform MD epithelium (MDE) differentiates into diverse epithelial cell types with unique morphology and functions in each organ. Classic tissue recombination studies, in which the epithelium and mesenchyme isolated from the newborn mouse FRT were recombined, have established that the organ specific epithelial cell fate of MDE is dictated by the underlying mesenchyme. The tissue recombination studies have also demonstrated that there is a narrow developmental window for the epithelial cell fate determination in MD-derived organs. Accordingly, the developmental plasticity of epithelial cells is mostly lost in mature FRT. If the signaling that controls epithelial differentiation is disrupted at the critical developmental stage, the cell fate of MD-derived epithelial tissues will be permanently altered and can result in epithelial lesions in adult life. A disruption of signaling that maintains epithelial cell fate can also cause epithelial lesions in the FRT. In this review, the pathogenesis of cervical/vaginal adenoses and uterine squamous metaplasia is discussed as examples of such incidences. Copyright © 2011. Published by Elsevier B.V.

PMID 21612855

The prevalence of congenital uterine anomalies in unselected and high-risk populations: a systematic review

Hum Reprod Update. 2011 Nov-Dec;17(6):761-71. Epub 2011 Jun 24.

Chan YY, Jayaprakasan K, Zamora J, Thornton JG, Raine-Fenning N, Coomarasamy A. Source Department of Obstetrics and Gynaecology, Nottingham University Hospitals NHS Trust, Queen's Medical Centre Campus, Derby Road, Nottingham NG7 2UH, UK. yeeyin@gmail.com Abstract BACKGROUND: The prevalence of congenital uterine anomalies in high-risk women is unclear, as several different diagnostic approaches have been applied to different groups of patients. This review aims to evaluate the prevalence of such anomalies in unselected populations and in women with infertility, including those undergoing IVF treatment, women with a history of miscarriage, women with infertility and recurrent miscarriage combined, and women with a history of preterm delivery. METHODS: Searches of MEDLINE, EMBASE, Web of Science and the Cochrane register were performed. Study selection and data extraction were conducted independently by two reviewers. Studies were grouped into those that used 'optimal' and 'suboptimal' tests for uterine anomalies. Meta-analyses were performed to establish the prevalence of uterine anomalies and their subtypes within the various populations. RESULTS: We identified 94 observational studies comprising 89 861 women. The prevalence of uterine anomalies diagnosed by optimal tests was 5.5% [95% confidence interval (CI), 3.5-8.5] in the unselected population, 8.0% (95% CI, 5.3-12) in infertile women, 13.3% (95% CI, 8.9-20.0) in those with a history of miscarriage and 24.5% (95% CI, 18.3-32.8) in those with miscarriage and infertility. Arcuate uterus is most common in the unselected population (3.9%; 95% CI, 2.1-7.1), and its prevalence is not increased in high-risk groups. In contrast, septate uterus is the most common anomaly in high-risk populations. CONCLUSIONS: Women with a history of miscarriage or miscarriage and infertility have higher prevalence of congenital uterine anomalies compared with the unselected population.

PMID 21705770

2009

Müllerian duct anomalies and mimics in children and adolescents: correlative intraoperative assessment with clinical imaging

Radiographics. 2009 Jul-Aug;29(4):1085-103.

Junqueira BL, Allen LM, Spitzer RF, Lucco KL, Babyn PS, Doria AS.

Department of Diagnostic Imaging, Hospital for Sick Children, 555 University Ave, Toronto, ON, Canada M5G 1X8. Abstract Müllerian duct anomalies (MDAs) are congenital entities that result from nondevelopment, defective vertical or lateral fusion, or resorption failure of the müllerian (paramesonephric) ducts. MDAs are common, although the majority are asymptomatic, and have been classified by the American Society of Reproductive Medicine according to clinical manifestations, prognosis, and treatment. Accurate diagnosis of an MDA is essential, since the management approach varies depending on the type of malformation. In females, when a müllerian duct becomes obstructed, the patient may present with an abdominal mass and dysmenorrhea. If the patient is not treated in a timely fashion, the consequences can be severe, extending even to infertility. When an MDA is suspected, ultrasonography (US) should be performed initially to delineate any abnormalities in the genital tract. However, US cannot help identify the type of MDA. In contrast, magnetic resonance imaging is a valuable technique for noninvasive evaluation of the female pelvic anatomy and accurate MDA classification. If obstruction is present, surgical correction of the MDA may be required, and further counseling of the patient with regard to reproductive possibilities becomes important. Supplemental material available at http://radiographics.rsnajnls.org/cgi/content/full/29/4/1085/DC1.

Copyright RSNA, 2009

PMID: 19605658 http://www.ncbi.nlm.nih.gov/pubmed/16272225

http://radiographics.rsna.org/content/29/4/1085.long

--Mark Hill 16:18, 14 December 2010 (EST) Good illustrated review of uterine abnormalities.

2007

Physiology of upward transport in the human female genital tract

Zervomanolakis I, Ott HW, Hadziomerovic D, Mattle V, Seeber BE, Virgolini I, Heute D, Kissler S, Leyendecker G, Wildt L. Ann N Y Acad Sci. 2007 Apr;1101:1-20. Epub 2007 Apr 7. PMID: 17416925 [PubMed - indexed for MEDLINE]


The uterus and fallopian tubes represent a functionally united peristaltic pump under the endocrine control of ipsilateral ovary. We have examined this function by using hysterosalpingoscintigraphy (HSS), recording of intrauterine pressure, electrohysterography, and Doppler sonography of the fallopian tubes. An uptake of labeled particles into the uterus was observed during the follicular and luteal phases of the cycle after application into the vagina. Transport into the oviducts, however, could only be demonstrated during the follicular phase. Furthermore, the predominant transport was into the tube ipsilateral to the ovary containing the dominant follicle. The pregnancy rate following spontaneous intercourse or insemination was higher in those women in whom ipsilateral transport could be demonstrated. The amount of material transported to the ipsilateral tube was increased after oxytocin administration, as demonstrated by radionuclide imaging and by Doppler sonography following instillation of ultrasound contrast medium. An increase in the basal tone and amplitude of contractions was observed after oxytocin administration. These results support the idea that the uterus and fallopian tubes act as a peristaltic pump, which increases transport of sperm into the oviduct ipsilateral to the ovary bearing the dominant follicle. Oxytocin appears to play a critical role in this peristaltic pump. A failure of the peristaltic mechanism is possibly responsible for infertility. We propose the term tubal transport disorder (TTD) as a nosological entity. Results from HSS could be a useful adjunct for choosing treatment modalities in patients with patent fallopian tubes suffering from infertility. These patients may be better served with in vitro fertilization (IVF).


Role of the oviduct in sperm capacitation

Rodriguez-Martinez H. Theriogenology. 2007 Sep 1;68 Suppl 1:S138-46. Epub 2007 Apr 23. Review. PMID: 17452049 [PubMed - indexed for MEDLINE]

Following insemination of spermatozoa pre-ovulation, the mammalian oviduct ensures, by the formation of a functional sperm reservoir (SR), that suitable (low) numbers of viable and potentially fertile spermatozoa are available for fertilization at the ampullary isthmic junction (AIJ). As ovulation approaches, a proportion of the SR-stored spermatozoa is continuously distributed towards the AIJ and individually activated leading to step-wise capacitation and the attainment of hyperactivated motility. This paper reviews in vivo changes in the intra-luminal milieu of the oviduct of pigs and cows, in particular the SR and the AIJ which relate to the modulation of sperm capacitation around spontaneous ovulation. In vivo, most viable spermatozoa in the pre-ovulatory SR are uncapacitated. Capacitation rates significantly increase after ovulation, apparently not massively but concurrent with the individual, continuous sperm dislocation from the SR. Bicarbonate, whose levels differ between the SR and the AIJ, appears as the common primary effector of the membrane destabilizing changes that encompasses the first stages of capacitation. Sperm activation can be delayed or even reversed by co-incubation with membrane proteins of the tubal lining, isthmic fluid or specific tubal glycosaminoglycans, such as hyaluronan. Although the pattern of response to in vitro induction of sperm activation - capacitation in particular - is similar for all spermatozoa, the capacity and speed of the response is very individual. Such diversity in responsiveness among spermatozoa insures full sperm viability before ovulation and the presence of spermatozoa at different stages of capacitation at the AIJ, thus maximizing the chances of normal fertilization.


2006

Sperm transport in the female reproductive tract

Suarez SS, Pacey AA. Hum Reprod Update. 2006 Jan-Feb;12(1):23-37. Epub 2005 Nov 4. Review.

PMID 16272225


2005

Microscopical survey of the development and differentiation of the epithelium of the uterine tube and uterus in the human fetus

Ital J Anat Embryol. 2005;110(2 Suppl 1):231-7.

Barberini F, Correr S, Makabe S. Source Laboratory of Electron Microscopy Pietro M. Motta, Department of Anatomy, University of Rome La Sapienza, Rome, Italy. fabrizio.barberini@uniroma1.it Abstract The development and differentiation of the coelomic epithelium lining the paramesonephric ducts in human fetus, that gives rise to the female genital organs, have been ultrastructurally examined. The epithelium appeared pseudostratified, consisting of basal, microvillous and ciliated cells. In younger fetuses (12th gestational week) ciliogenic elements could be detected mainly on the developing tubal fimbriae, but most of the cells showed microvilli and often single cilia. In the subsequent phases of development, morphodynamics of cell renewal were documented by aspects of apoptosis. Fully ciliated cells were numerous on the fimbriae and at the utero-tubal junction, but not in the uterus; however, these were less abundant than those showing microvillous. In older fetuses (31st gestational week) microapocrine secretion by microvillous cells, in the form of droplets contacting cilia, could be observed. In the same fetuses the ectocervix was covered by a mature squamous epithelium, made up of polygonal flat desquamating cells, showing labyrinthine surface microplicae. Our observations demonstrated that ciliation in the human female genital organs, like that of other systems, is neither simultaneous nor uniform, and ciliated cells are gathered preferentially in strategic sites, to mediate germ cell migration and blastocyst implantation in adult life. These ultrastructural data seem to indicate that the female genital tract epithelium, at least in its general features, is sketched since fetal life, and cell morphodynamics, including microvillous and ciliated cell differentiation, as well as the secretory activity, are the morphological expression of the complex molecular mechanisms, involved in developmental biology and reproductive physiology. PMID 16101043

2001

Developmental biology of uterine glands

Biol Reprod. 2001 Nov;65(5):1311-23.

Gray CA1, Bartol FF, Tarleton BJ, Wiley AA, Johnson GA, Bazer FW, Spencer TE.

Abstract

All mammalian uteri contain endometrial glands that synthesize or transport and secrete substances essential for survival and development of the conceptus (embryo/fetus and associated extraembryonic membranes). In rodents, uterine secretory products of the endometrial glands are unequivocally required for establishment of uterine receptivity and conceptus implantation. Analyses of the ovine uterine gland knockout model support a primary role for endometrial glands and, by default, their secretions in peri-implantation conceptus survival and development. Uterine adenogenesis is the process whereby endometrial glands develop. In humans, this process begins in the fetus, continues postnatally, and is completed during puberty. In contrast, endometrial adenogenesis is primarily a postnatal event in sheep, pigs, and rodents. Typically, endometrial adenogenesis involves differentiation and budding of glandular epithelium from luminal epithelium, followed by invagination and extensive tubular coiling and branching morphogenesis throughout the uterine stroma to the myometrium. This process requires site-specific alterations in cell proliferation and extracellular matrix (ECM) remodeling as well as paracrine cell-cell and cell-ECM interactions that support the actions of specific hormones and growth factors. Studies of uterine development in neonatal ungulates implicate prolactin, estradiol-17 beta, and their receptors in mechanisms regulating endometrial adenogenesis. These same hormones appear to regulate endometrial gland morphogenesis in menstruating primates and humans during reconstruction of the functionalis from the basalis endometrium after menses. In sheep and pigs, extensive endometrial gland hyperplasia and hypertrophy occur during gestation, presumably to provide increasing histotrophic support for conceptus growth and development. In the rabbit, sheep, and pig, a servomechanism is proposed to regulate endometrial gland development and differentiated function during pregnancy that involves sequential actions of ovarian steroid hormones, pregnancy recognition signals, and lactogenic hormones from the pituitary or placenta. That disruption of uterine development during critical organizational periods can alter the functional capacity and embryotrophic potential of the adult uterus reinforces the importance of understanding the developmental biology of uterine glands. Unexplained high rates of peri-implantation embryonic loss in humans and livestock may reflect defects in endometrial gland morphogenesis due to genetic errors, epigenetic influences of endocrine disruptors, and pathological lesions.

PMID 11673245

Formation of Fallopian tubal fluid: role of a neglected epithelium

Leese HJ, Tay JI, Reischl J, Downing SJ. Reproduction. 2001 Mar;121(3):339-46. Review. PMID: 11226059


1999

The fetal development of the human uterine cervix from the 12th to the 31st postmenstrual week as revealed by scanning electron microscopy. Anatomical and clinical correlations

Ital J Anat Embryol. 1999 Jul-Sep;104(3):77-87.

Barberini F, Makabe S, Correr S, Motta PM. Source Department of Human Anatomy, University of Rome La Sapienza, Italy.

Abstract

To clarify the differentiation of the human uterine cervix, fetuses of the 12th, 15th, 18th, 20th, 21st, 22nd, and 31st postmenstrual week were studied by Scanning Electron Microscopy. At the 12th week the endocervical epithelium consisted of microvillous cells, often showing single cilia and anlages of tubular glands. At the 15th week the cervical canal was entirely formed and its surface cells appeared columnar. At the 18th week these cells were replaced by flat or slightly raised cells, provided with thin microplicae. At the 20th week the endocervical epithelium appeared pseudostratified with higher, apically-convex and shorter basal cells; glands developed in form of tubular invaginations of the luminal epithelium. At the 21st week in the lower part of the endocervix polymorphic, globose cells with short and stubby microvilli and others elongated, having short microplicae, were observed. These latter likely corresponded to the so-called columnar cells undergoing squamous metaplasia. Among microvillous and/or metaplastic cells, a number of apoptotic cells, as globose elements with a ruffled and invaginated surface, were also noted. At the 22nd week evident plicae palmatae were found, covered by microvillous secreting cells. These showed smooth bulged apices releasing droplets by a "micro-apocrine" mechanism. These features increased at the 31st week, when many droplets were noted also around the mouth of the cervical glands. Only at this phase of development fully ciliated cells were found often contacting secretory material. Mature squamous exfoliating cells with complex microplicae covered an hypertrophied portio vaginalis. The squamous cells extended toward a squamo-columnar junction in form of flat, tongue-like projections. Their tips consisted of immature squamous metaplastic cells, which were endocervical columnar progressively becoming elongated elements, exhibiting short microvilli. The above features are rather similar to those occurring during the adult reproductive age. Therefore, it might be hypothesized that, during pregnancy, a common gestational hormonal background may induce somewhat similar morpho-dynamic processes in the cells and tissues of the fetal reproductive tract mimicking what occurs in the adult female.

PMID 10575820


1994

An ultrastructural study of epithelium differentiation in the human fetal fallopian tube

Acta Anat (Basel). 1994;151(4):207-19.

Barberini F, Makabe S, Correr S, Luzi A, Motta PM. Source Department of Anatomy, University of Rome La Sapienza, Italy.

Abstract

The epithelial structure of the developing human fetal Fallopian tube has been studied systematically by parallel light, transmission and scanning electron microscopy. The specimens for this study were collected from spontaneous abortions at the 14th, 18th, 20th and 22nd weeks and from cases of intrauterine fetal death at the 24th and 31st weeks (hydrocephalus). The epithelium lining the wall of the female genital ducts was pseudostratified in a columnar fashion. It consisted of differentiating ciliated and microvillous cells and some degenerating elements. Microvillous cells-by far the most abundant in the early phases of tubal development-often showed a solitary cilium. Ciliated elements, though always less numerous than microvillous cells, were more densely concentrated on the developing fimbriae and at the uterotubal junction than in the ampulla. On the mucosal surface of the same regions, rounded intercellular holes delimited many crypts, from which ciliated elements sometimes sprouted. Notable aspects of cell proliferation and ciliogenesis were commonly observed and are likely to be related to circulating estrogens. These ultrastructural data indicate that the typical pattern of the adult oviduct is already sketched in fetal life. Furthermore, a strategic gathering of cilia was noted primarily at the sites of the developing oviduct, which will serve to mediate the passage of sperm and/or ova and promote fertilization in adult life.

PMID 7740916



New aspects of gamete transport, fertilization, and embryonic development in the oviduct gained by means of live cell imaging. Kölle S, Reese S, Kummer W. Theriogenology. 2010 Apr 1;73(6):786-95. Epub 2010 Jan 18. Review. PMID: 20080295 [PubMed - indexed for MEDLINE] Related citations 2. Ciliary transport, gamete interaction, and effects of the early embryo in the oviduct: ex vivo analyses using a new digital videomicroscopic system in the cow. Kölle S, Dubielzig S, Reese S, Wehrend A, König P, Kummer W. Biol Reprod. 2009 Aug;81(2):267-74. Epub 2009 Mar 18. PMID: 19299315 [PubMed - indexed for MEDLINE] Related citations 3. [Role of the female environment in sperm capacitation] Patrat C, Serres C. Gynecol Obstet Fertil. 2009 Jun;37(6):536-9. Epub 2009 May 20. French. PMID: 19467904 [PubMed - indexed for MEDLINE] Related citations 4. Contributions to myometrium study in uterine-tubal junction. Neamţu MC, Neamţu RL, Avramescu ET, Vrabete M, Călina LM, Mîndrilă I. Rom J Morphol Embryol. 2009;50(4):675-81. PMID: 19942965 [PubMed - indexed for MEDLINE]Free Article Related citations 5. Fertilization and early embryonic development in the porcine fallopian tube. Brüssow KP, Rátky J, Rodriguez-Martinez H. Reprod Domest Anim. 2008 Jul;43 Suppl 2:245-51. Review. PMID: 18638131 [PubMed - indexed for MEDLINE] Related citations 6. Regulation of sperm storage and movement in the mammalian oviduct. Suarez SS. Int J Dev Biol. 2008;52(5-6):455-62. Review. PMID: 18649258 [PubMed - indexed for MEDLINE]Free Article Related citations

9. Sperm binding glycoprotein is differentially present surrounding the lumen of isthmus and ampulla of the pig's oviduct. Pérez FA, Roma SM, Cabada MO, Marini PE. Anat Embryol (Berl). 2006 Nov;211(6):619-24. Epub 2006 Sep 1. PMID: 16947066 [PubMed - indexed for MEDLINE] Related citations 10. Relationship between the fertile period and sperm transport in the bitch. England GC, Burgess CM, Freeman SL, Smith SC, Pacey AA. Theriogenology. 2006 Oct;66(6-7):1410-8. Epub 2006 Mar 15. Review. PMID: 16540160 [PubMed - indexed for MEDLINE] Related citations 11. Gamete/embryo - oviduct interactions: implications on in vitro culture. Lee KF, Yeung WS. Hum Fertil (Camb). 2006 Sep;9(3):137-43. Review. PMID: 17008265 [PubMed - indexed for MEDLINE] Related citations 12. Oviductal motile response to penile cervical buffeting. Shafik A, Shafik I, El Sibai O, Shafik AA. Arch Gynecol Obstet. 2006 Jan;273(4):216-20. Epub 2005 Sep 16. PMID: 16167158 [PubMed - indexed for MEDLINE] Related citations


http://www.ncbi.nlm.nih.gov/pubmed/7004702

PIP: The anatomy and physiology of the human fallopian tube are described and discussed; then, these facts are correlated with clinical considerations as they relate to tubal factor infertility. Anatomically the human oviduct is a tubular, seromuscular organ attached distally to the ovary and proximally to the lateral aspect of the uterine fundus. Its length averages 11-12 cm. The oviduct can be divided into 4 main segments: 1) the infundibulum, whose terminal end contains the tubal ostium; 2) the ampullary region; 3) the isthmic portion; and 4) the intramural or interstitial portion, which is contained in the wall of the uterus. 4 electron micrographs illustrate these areas. Also discussed in this reveiw are the vascular analtomy, the lymphatics, and neuroanatomy of the fallopian tubes. Physiologic functions discussed in this article include the role of the fallopian tube in sperm transport, its part in sperm maintenance and capacitation, and the tube's function in ovum transport, fertilization, and embryo transport. Clinically, the role of the myosalpinx is undetermined, although it may affect tubal motility and ovum transport. The dense adrenergic innervation of the oviductal isthmus, along with the myosalpinx, suggests that innervation may be required for sphincter-like activity, although again no evidence exists for innervation being required in normal reproduction. The mucosa provides nutrients which may or may not be essential to normal reproduction, and its cilia seems uncritical in gamete transport and embryogenesis. Evidence shows that the uterotubal junction and the ampullary-isthmic junction are not necessary for conception (based on success rates of implantation procedures). Reversal of fimbriectomy is the most difficult and up to 1-cm of ampulla may be removed and resected and still maintain fertility.


Effects of transmaternal exposure to genistein in Hatano high- and low-avoidance rats. Ohta R, Shirota M, Kanazawa Y, Shindo T, Furuya M, Seki T, Ono H, Kojima K, Asai S, Watanabe G, Taya K. Exp Anim. 2009 Oct;58(5):471-9. PMID: 19897930 [PubMed - indexed for MEDLINE]Free Article


Recurrent microdeletion at 17q12 as a cause of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome: two case reports. Bernardini L, Gimelli S, Gervasini C, Carella M, Baban A, Frontino G, Barbano G, Divizia MT, Fedele L, Novelli A, Béna F, Lalatta F, Miozzo M, Dallapiccola B. Orphanet J Rare Dis. 2009 Nov 4;4:25. PMID: 19889212 [PubMed - indexed for MEDLINE]Free PMC ArticleFree text


Expression of nodal signalling components in cycling human endometrium and in endometrial cancer. Papageorgiou I, Nicholls PK, Wang F, Lackmann M, Makanji Y, Salamonsen LA, Robertson DM, Harrison CA. Reprod Biol Endocrinol. 2009 Oct 29;7:122. PMID: 19874624 [PubMed - indexed for MEDLINE]Free PMC ArticleFree text


Stretch activates human myometrium via ERK, caldesmon and focal adhesion signaling. Li Y, Reznichenko M, Tribe RM, Hess PE, Taggart M, Kim H, DeGnore JP, Gangopadhyay S, Morgan KG. PLoS One. 2009 Oct 16;4(10):e7489. PMID: 19834610


Specific subsets of immune cells in human decidua differ between normal pregnancy and preeclampsia - a prospective observational study

http://www.rbej.com/content/7/1/132

Cervix

Slides 22 and 23 histology of the cervix

  • The cervix is lined by stratified squamous epithelium AND mucinous columnar epithelium
  • endocervix by columnar epithelium
  • ectocervix by squamous
  • relevance to the transformation zone.





Terms

abdomen - trunk between diaphragm and pelvis.

abdominal circumference - An ultrasound measurement of Abdominal Circumference (AC) is used to determine fetal age and normal development (small/large/abnormal) parameters. Measured at the outer edge of the circumference of the body plane in which the portal vein or stomach can be visualized in a tangential section. It is one of the four typical ultrasound assessments of fetal size and age: Biparietal Diameter (BPD), Head Circumference (HC), Abdominal Circumference (AC), and Femur Length] (FL). Abdominal Circumference of less than 31 cm at 36 to 40 weeks gestation is a predictor of intrauterine growth retardation (IUGR).

AC - Acronym for Abdominal Circumference.

adenohypophysis - (anterior pituitary, pars distalis) The anterior part of the pituitary, which develops in the early embryo from a transient region on the roof of the pharynx called Rathke's pouch.

adnexa - (Latin, adnexae = appendages) Term used to describe any anatomical appendage (accessory structure, extension or outgrowth from the body). In reproductive anatomy used to describe appendages of the [U.htm#uterus uterus] "body"; ovaries, uterine tubes and uterus supporting ligaments.

adrenal gland - (suprarenal gland) The endocrine organ that anatomically sits on top of the kidneys (renal). It has two different embryonic origins, neurat crest (aderenal medulla) and mesoderm (adrenal cortex).

adventitia - Anatomical term describing the outermost connective tissue covering of any organ, vessel, or other structure not covered by a serosa. The covering is from the surrounding connective tissue and does not form an integral part of such organ or structure.

amnion - An extraembryonic membrane ectoderm and extraembryonic mesoderm in origin and forms the innermost fetal membrane, produces amniotic fluid. This fluid-filled sac initially lies above the trilaminar embryonic disc and with embryoic disc folding this sac is drawn ventrally to enclose (cover) the entire embryo, then fetus. The presence of this membrane led to the description of reptiles, bird, and mammals as amniotes.

amniotic fluid - The fluid that fills amniotic cavity totally encloses and cushions the embryo. Amniotic fluid enters both the gastrointestinal and respiratory tract following rupture of the buccopharyngeal membrane. The late fetus swallows amniotic fluid.

ampulla - Term used to describe an anatomical dilation of a tube or canal lumen. Anatomical description of the opening end of the uterine tube lying above the ovary and the enlarged initial segmeny of the semicircular canals of the inner ear vestibular system.

anastomosis - Term used to describe the connection between two tubes. Applied to describe the connection between peripheral blood vessels without an intervening capillary bed.

androgens - The male sex hormones, eg testosterone.

anterior - Anatomical term used to describe the front or ventral surface.

Anti-Mullerian Hormone - (AMH, Mullerian Inhibiting Substance, MIS) A secreted factor (transforming growth factor-beta, TGF-beta superfamily) that regulates gonadal and genital tract development. Inhibits paramesonephric (Mullerian) duct development in males. (More? OMIM - AMH)

antral follicle - (secondary follicle) Term used to describe the developmental stage of ovarian follicle development following preantral (primary) in describing the sequence (primordial, preantral, antral) of follicle development within the ovary. In humans, a number of primordial follicles will begin to develop into primary follicles, some of which will then form antral follicles (secondary), with only a single antral follicle developing into the ovulating follicle (Graafian) each menstrual cycle.

antrum - (Latin from Greek, antron = a cave, cavity; a nearly-closed cavity or bulge). Identified anatomically in many structures (ovarian follicle, bone, cardiac, gastric). In the ovary this refers to the follicular fluid-filled space within the follicle.

atresia - (Greek, a = without + tresis = perforation) Term used for anatomical closing or absence of a cavity or opening that should exist. Used as an antomical, pathological and clinical term: esophageal atresia, biliary atresia, duodenal atresia, jejunal atresia, choanal atresia, vaginal atresia, urethral atresia, pulmonary atresia, bronchial atresia, tricuspid atresia.

autosomal - The term decribing all the chromosomes that contribute to a cell's genetic material, except for the sex chromosomes X, Y.

autosomal inheritance - Some hereditary diseases are described as autosomal which means that the disease is due to a DNA error in one of the 22 pairs that are not sex chromosomes. Both boys and girls can then inherit this error. If the error is in a sex chromosome, the inheritance is said to be sex-linked.

birth - (parturition) Term describing the pysiological process of offspring (child) being born.

bladder exstrophy - (Greek, ekstriphein = "turn inside out") A congenital malformation with bladder open to ventral wall of abdomen (between umbilicus and pubic symphysis) and may have other anomolies associated with failure of closure of abdominal wall and bladder (epispadias, pubic bone anomolies).

Bulbourethral Gland - (= Cowper's Gland) A male genital tract gland which secretes a small amount of a thick clear mucous fluid prior to ejaculation, the alkaline content apparently buffers acidity of the urethra. The equivalent female gland are Bartholin's glands.

caudal - (Latin, caudal = tail) Anatomical term referring to structures that are more towards the tail.

chryptochid testes - A male genital abnormality where the testes remain undescended in the abdominopelvic cavity.

ciliated epithelium - (Latin, cilium = eyelid) An epithelium named on the basis of the cells having surface hair-like appearance of a cilium; singular, cilium. In many tissues, cilia are found as epithelial cell apical surface motile specializations. In the uterine tube epithelium, after ovulation used to move the unfertilized egg, then the fertilized zygote, then blastocyst during the first week of development.

cloacal membrane - Forms the external lower membrane limit (caudal end) of the early gastrointestinal tract (GIT). This membrane is formed during gastrulation by ectoderm and endoderm without a middle (intervening) layer of mesoderm. The membrane breaks down to form the initial "anal opening" of the gastrointestinal tract.

coelom - Term used to describe a space. There are extraembryonic and intraembryonic coeloms that form during vertebrate development. The single intraembryonic coelom will form the 3 major body cavities: pleural, pericardial and peritoneal. (More? [Coelom Development]])

congenital - Already present at birth, often used to describe defects present at birth, congenital defects.

congenital adrenal hyperplasia - (CAH, adrenal virilism) Abnormality of the fetal adrenal cortex, alters cortisol and androgens with different effects dependent upon sex: in females masculization of the external genitalia; in males, disorder often unnoticed until postnatally. In both sexes, accelerated skeletal growth and sexual maturation is seen in late childhood.

corticosteroid - A steroidal hormone produced by the adrenal cortex.

critical period - (critical period of development) The term used to describe a developmental time when exposure to a teratogen can lead to a developmental abnormality, which can be further divided into an early major and later minor developmental abnormality. The defined critical period will differ in timing and length for different systems.

CRL - Acronym for Crown-Rump Length. Used in embryology to accurately stage the early embryo. Used in clinical ultrasound as a measurement between the periods of 7 to 13 weeks as an accurate estimation of the gestational age.

dihydrotestosterone - The hormonally active form of testosterone (male sex hormone) produced by enzyme (5-alpha reductase) conversion. In the male embryo, this can occur in the genital skin which then supports external genital development. In the adult, this conversion occurs in a number of different tissues. A known treatment for prostate cancer include 5-alpha reductase inhibitors.

ectoderm - (Greek, ecto = outside + derma = skin) One of the initial 3 germ cell layers, which will form the nervous system from the neural tube and neural crest and also generates the entire epithelial layer of the skin covering the embryo. (More? Week 3)

embryology - (Greek, en = in + bryein = to be full of) The science of studying embryo development, usually applied to all development before birth (in humans, included both the embryonic and fetal period).

endocrine - (Greek, endon = within) Glands which release hormones into the blood stream. There are many specialized organs and tissues that release hormones into the bloodstream.

endocrine gland - (Greek, endon = within) A gland (organ, tissue) that is specialized for secretion of a hormone into the bloodstream for general circulation.

endoderm - (Greek, endo = inside + derma = skin) One of the initial 3 germ cell layers, formed by the process of gastrulation. The endoderm forms as a cuboidal epithelium and contributes not only to the trilaminar embryo, but also lines the yolk sac. It will form the entire epithelial lining of the gastrointestinal tract (GIT), contribute to the accessory organs of GIT and also forms the epithelial lining of the respiratory tract. Note that in the GIT it contributes both epithelium and the associated epithelial glands. In humans, endoderm forms during week 3 of development.

epiblast - (Greek, epi = above, upon) the layer (of the bilaminar embryo) that generates endoderm and mesoderm by migration of cells through the primitive streak. The remaing cells form ectoderm.

epithelium - (Greek, epi = upon + thele = nipple) Cells tightly linked together to form a sheet with little extracellular matrix. Most epithelia (plural) in the body are embryonically derived from ectoderm or endoderm germ layers. Note: not "skin" which is the epithelium and includes the underlying connective tissue layers (mesoderm) and melanocytes (neural crest) forming a complex tissue.

epoophoron - (rete ovarii, broad ligament cyst) A group of epithelial tubules that can be located in the mesosalpinx possibly mesonephric in origin. Occurs when a segment of the mesonephric duct remains in the female, associated with either the ovary and broad ligament. This "male remnant" will appear as a cyst (broad ligament cyst, adnexal papillary cystadenoma of probable mesonephric origin, APMO) with an appearance that differs depending upon the state of differentiation when the original abnormality occurred.

estrogens - Sex hormone found in both male and female. In the female, this hormone is produced by the ovaries and is responsible for development of secondary feminine sex characteristics. Together with progesterone these hormones also regulate changes that occur each menstral cycle. In the male, Leydig cells produce estrogen into the rete testis fluid at variable levels in different species. During male embryonic development exposure to high levels of estrogen can lead to genital abnormalities.

exstrophy - (Greek, ekstriphein = "turn inside out", bladder exstrophy, cloacal exstrophy) Term used to describe developmental abnormalities where the structure has been anatomically inverted. For example, bladder exstrophy, a congenital malformation with bladder open to ventral wall of abdomen (between umbilicus and pubic symphysis) and may have other anomolies associated with failure of closure of abdominal wall and bladder (epispadias, pubic bone anomolies).

exstrophy of the bladder - See bladder exstrophy

extraembryonic membrane - Term used to describe each of the amnion, yolk sac, allantois and chorion membranes. [index/A.htm#amnion Amniotic membrane], ectoderm origin innermost membrane, produces amniotic fluid (reptiles, bird, and mammals are amniotes). [index/A.htm#yolk_sac Yolk sac], endoderm origin, associated with nutrition in reptiles and birds (mammals source of primordial germ cells and blood cells). [index/A.htm#allantois Allantois], endoderm origin, in reptiles and birds acts as a reservoir for wastes and mediates gas exchange; in mammals is associated/incorporated with connecting stalk/placental cord fetal-maternal interface. [index/C.htm#chorion Chorioic membrane], mesoderm origin, outermost layer in reptiles and birds acts in gas exchange; in mammals incorporated into the placenta and its functions.

extraembryonic mesoderm - Cells from the conceptus that contribute to placenta and fetal membranes. Described as "extraembryonic" because it is tissue lying outside the embryonic trilaminar disc (ectoderm, mesoderm and endoderm) and "mesoderm", because of the connective tissue cellular organization.

fallopian tube - (see [#uterine_tube uterine tube], uterine horn, oviducts) A pair of tubular structures designed to transport the oocyte (egg) from the ovary to the [U.htm#uterus uterus] body, named after Gabriel Fallopius (1523-1562), an anatomists and physician.

fetal period - (foetal period) In humans, the development week 9 to 36 is the fetal stage (second and third trimester) and during this time organs formed in the embryonic period continue to develop and the fetus grows in size and weight. The first 8 weeks of development is considered the embryonic period and is divided into 23 Carnegie stages based upon developmental milestones. Note when searching an alternate spelling "foetal".

fetus - (foetus) In mammals, term describes the period of development following the embryonic period. In humans, the development week 9 to 36 is the fetal stage (second and third trimester).

fimbriae - (Latin, fimbria = a fringe) The finger-like projections at the ovarian end of uterine tube. At ovulation they sit over the ovary to aid egg movement into the uterine tube.

Finasteride - A chemical used to prevent male pattern baldness and enlargement of prostate glands. An anti-androgen (blocks synthesis of dihydrotestosterone) and therefore a potential endocrine disruptor, exposed pregnant women can impact on male fetus genetial development.

first trimester - Clinical term used to describe and divide human pregnancy period (9 months) into three equal parts of approximately three calendar months. The first trimester corresponds approximately to embryonic development (week 1 to 8) of organogenesis and early fetal. The second and third trimester correspond to the fetal period of growth in size (second trimester) and weight (third trimester), as well as continued differentiation of existing organs and tissues.

follicle - (Latin, folliculus = little bag, dim. of Latin follis) The functional unit within the ovary that includes the developing oocyte (egg) and the surrounding layers of cells that support that oocyte. Some cells within the follicle are released along with the ooctye at ovulation, while other cells are involved with female sex hormone secretion into the maternal bloodstream.

follicle stimulating hormone - (FSH, gonadotropin) Glycoprotein hormone secreted by anterior pituitary and acts on gametogenesis and other systems in both males and females. In females, FSH acts on the ovary to stimulate follicle development. Negative feedback by inhibin from the developing follicle decreases FSH secretion. In males, acts on the testis Sertoli cells to increase androgen-binding protein (ABP) that binds androgens and has a role in spermatogenesis. FSH-deficientcy in females results in infertile (block in folliculogenesis prior to antral follicle formation) and in males does not affect fertility (have small testes but are fertile). FSH protein has a molecular weight 30 kDa and a 3-4 hour half-life in circulation. Gonadotrophins have been used clinically in humans for the treatment of infertility. Other glycoproetin hormones include luteinizing hormone (LH), thyroid stimulating hormone (TSH), and chorionic gonadotropin. (More? Kumar TR, Wang Y, Lu N, Matzuk MM. Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nat Genet. 1997 Feb;15(2):201-4.)

folliculogenesis - The term used to describe the process of follicle development within the ovary. The follicle is the structure developing within the ovary that includes the oocyte (egg) and surrounding support cells.

gametes - (Greek, gamos = marriage) A specialized reproductive cell through which sexually reproducing parents pass chromosomes to their offspring; a sperm or an egg.

gameteogenesis - The production of either the haploid germ cells of spermatazoa (male) or eggs (female).

Gartner's duct - a female developmental abnormality caused by the persistance of the mesonephric duct (normally lost in females) when the ureteric bud fails to separate from the mesonephric duct. Can generate a broad ligament or vaginal cyst. Named after Hermann Treschow Gartner (1785-1827) a Danish surgeon and anatomist.

gene - A DNA sequence that is transcribed as a single unit and encodes a single polypeptide (protein) or a set of closely related polypeptides. There are approximately 20,000-25,000 protein encoding genes in the human genome. In each cell, DNA is found within the nucleus and also within mitochondria.

genitalia - (Latin, genitalia = ) The term used to describe either the external or internal male and female sexual and reproductive organs. (More? [urogen.htm Urogenital Notes])

genital tubercle - A prominence or rounded protuberance extending ventrally at the inferior end of the body of the embryo. It has initially a sexually indifferent external genitalia structure and contributes to either male (glans penis) and female (clitoris) external genitalia.

genome - The collection of all the DNA in an organism.

germ layers - The first three cellular layers (ectoderm, mesoderm, and endoderm) that will form all tissues of the embryo. In humans, these layers begin to form during week 3 of development. Term should not be confused with germ cells, which are the oocyte and spermatazoa forming cells. Named originally by Robert Remak (1815 - 1865) a German scientist and embryologist.

germinal epithelium - cellular component covering surface of ovary, it is continuous with mesothelium covering mesovarium. Note that it is a historical misnomer, as it is not the actual site of germ cell formation.

GHRH - Arconym for Growth Hormone Releasing Hormone, secreted by the Hypothalamus it is a protein that activates Growth Hormone synthesis and release from the pituitary.

gonad - (Greek, gonos = seed) A gamete-producing (germ cell) organ. A non-sexual term which is used to describe both the female ovary and male testis.

gonadotrophin releasing hormone - (Greek, gonos = seed) (GnRH) Hormone released from hypothalamus that stimulates pituitary gonadotropin synthesis and secretion (luteinizing hormone, LH and follicle stimulating hormone, FSH). The cyclic release of GnRH has been shown to differentially affect gonadotropin release (rapid frequency, more than 1 pulse / hour LH; slower frequencies FSH secretion). (More?Marshall JC, Eagleson CA, McCartney CR. Hypothalamic dysfunction. Mol Cell Endocrinol. 2001 Oct 25;183(1-2):29-32. Review.)

granulosa cell - A specific cell type that proliferates in association with the oocyte within the developing follicles of the ovary. These cells form the follicle stratum granulosa and are also given specific names based upon their position within the follicle. In the antral follicle, [index/M.htm#membrana_granulosa membrana granulosa] sits on the [index/F.htm#follicular_basal_lamina follicular basal lamina] and lines the antrum as a stratified epithelium. The [index/C.htm#cumulus_oophorus cumulus oophorus] isindex/ a column of granulosa cells that attaches the oocyte to the follicle wall. The [C.htm#corona_radiata corona radiata] are the granulosa cells that directly surround the oocyte, and are released along with it at ovulation. Following ovulation the corona radiata provide physical protection to the oocyte and granulosa cells within the ovulating follicle contribute to corpus luteum.

growth hormone - (GH) A peptide hormone, made in the anterior pituitary, that stimulates tissue and skeletal growth.

growth hormone releasing hormone - (GHRH) secreted by the hypothalamus it is a protein that activates Growth Hormone synthesis and release from the pituitary.

hCG - An acronym for the hormone human Chorionic Gonadotrophin.

hernia - A general discription of protrusion of an organ through a weak spot in the surrounding tissue. In normal development, herniated midgut, describes the gastrointestinal tract growth outside the abdominal wall prior to body wall growth. In abnormal development, abnormal protrusion of organs in the diaphragm, abdominal or groin areas (hiatal hernias or inguinal hernias).

herniated - The discription of the process of protrusion of an organ through a weak spot in the surrounding tissue. In normal development, herniated midgut, describes the gastrointestinal tract growth outside the abdominal wall prior to body wall growth. In abnormal development, abnormal protrusion of organs in the diaphragm, abdominal or groin areas (hiatal hernias or inguinal hernias). Occurs normally in the development of the gastrointestinal tract when the midgut is initially herniated at the umbilicus during embryonic development.

hilum - Term used to describe an anatomical depression in an organ where vessels and nerves enter or leave.

hindgut - The last of the three part/division ([F.htm#foregut foregut] - midgut - hindgut) of the early forming gastrointestinal tract. The hindgut forms all the tract from the distral transverse colon to the cloacal membrane and extends into the connecting stalk (placental cord) as the allantois. In addition, a ventral of the hindgut will also form the urinary tract (bladder, urethra) epithelium. (More? [git.htm Gastrointestinal Tract Notes] | [urogenital.htm Urogenital Notes])

hormone - A substance, made and released by cells in a specific organ or structure, that moves throughout the organism and exerts specific effects on specific cells in other organs or structures. (More? [endocrine.htm Endocrine Notes])

human chorionic gonadotrophin - (hCG) Placental hormone initially secreted by cells (syncitiotrophoblasts) from the implanting conceptus during week two, supporting the ovarian corpus luteum, which in turn supports the endometrial lining and therefore maintains pregnancy. Hormone can be detected in maternal blood and urine and is teh basis of many pregnancy tests. Hormone also stimulates the onset of fetal gonadal steroidogenesis, high levels are teratogenic to fetal gonadal tissues.

hyperplasia - An abnormal increase in organ due to cell proliferation.

hypospadia - A male external genital abnormality, which is the most common penis abnormality (1 in 300) resulting from a failure of male urogenital folds to fuse in various regions and are therefore classified by the location of the opening (meatus).

ICSH - acronym for [#interstitial_cell_stimulating_hormone Interstitial Cell Stimulating Hormone] an anterior pituitary hormone.

inferior - Anatomical term meaning below, beneath or lying below, a relative anatomical term.

interstitial cell stimulating hormone - (ICSH, gonadotropin, lutropin, Interstitial Cell Stimulating Hormone, ICSH) Glycoprotein hormone releasd from anterior pituitary hormone that acts on the gonad and has a role in male and female reproduction. In male, stimulates testis interstital cell (Leydig cell) production of testosterone. In female, increase in concentration during the menstrual cycle triggers ovulation (release of the oocyte).

intraembryonic coelom - The "horseshoe-shaped" space (cavity) that forms initially in the third week of development in the lateral plate mesoderm that will eventually form the 3 main body cavities: pericardial, pleural, peritoneal. The intraembryonic coelom communicates transiently with the extraembryonic coelom.

intrauterine - Term means lying within the uterus.

karyotype - (Greek, karyon = kernel or nucleus + typos = stamp) Term used to describe the chromosomal (genetic) makeup (complement) of a cell.

kidney - In humans the metanephros forms the final adult kidney. An excretory organ which also has endocrine functions.

Leydig cells - (interstitial cells) Testis (male gonad) cell which secrete testosterone, beginning in the fetus. These cells are named after Franz von Leydig (1821 - 1908) a German scientist who histologically described these cells.

ligamentum teres - (ligamentum teres uteri, Hunter's ligament) The round ligament of uterus which maintains the ventral uterine position.

lobule - Term used to describe a small lobe. Can be used to describe part of a gland, ear, organ structure.

luteinizing hormone - (LH, gonadotropin, lutropin, Interstitial Cell Stimulating Hormone, ICSH) Glycoprotein hormone releasd from anterior pituitary hormone that acts on the gonad and has a role in male and female reproduction. In female, increase in concentration during the menstrual cycle triggers ovulation (release of the oocyte). In male, stimulates testis interstital cell (Leydig cell) production of testosterone. Gonadotrophins have been used clinically in humans for the treatment of female infertility.

lutenizing hormone - alternative spelling, (LH, gonadotropin) - (LH, gonadotropin, lutropin, Interstitial Cell Stimulating Hormone, ICSH) Glycoprotein hormone releasd from anterior pituitary hormone that acts on the gonad and has a role in male and female reproduction. In female, increase in concentration during the menstrual cycle triggers ovulation (release of the oocyte). In male, stimulates testis interstital cell (Leydig cell) production of testosterone.

luteinizing hormone/chorionic gonadotropin receptor - (LHCGR) a G protein-coupled receptor expressed in male testis (Leydig cells) and female ovary (granulosa-lutein and theca cells).

medial - (Latin, medialis = middle) Anatomically towards the midline of the body or structure. The opposite term is lateral.

mesenchyme - Term used to describe the cellular organisation of undifferentiated embryonic connective tissue . Mesenchymal tissue is mainly derived from mesoderm and neural crest, which will form most of the adult connective tissues. This connective tissue organization contrasts with the other main form of cellular organization, epithelial tissue.

mesonephros - The second temporary stage of kidney development (pro-, meso-, meta-). The intermediate mesonephros develops and disappears with the exception of its duct, the mesonephric duct, which will form the male reproductive duct system. In males, the mesonephric tubules go on to form the ducts of the testis. In females, these degenerate. A few mesonephric tubules remain as efferent ductules in the male and vestigial remnants in the female.

mesonephric duct - (Wollfian duct) An early developing urogenital paired duct system that initially runs the length of the embryo, that will differentiate and form the male reproductive duct system (ductus deferens). In females, this duct degenerates occasionally some remnants may remain associated in broad ligament. (More? [genital.htm Genital Notes])

mesovarium - The mesentry of the ovary formed from a fold of the broad ligament that attaches the ovary.

metanephric mesenchyme - Metanephric mesenchyme caudal part of intermediate mesoderm that will develop into nephrons within the kidney. The intermediate mesoderm forms as an unsegmented strip running rostro-caudally between the somite and lateral plate mesoderm. The very caudal (tail) end of this mesoderm strip where the uteric bud forms is the metanephric mesenchyme, which induces the formation of, and surrounds the end of, the ureteric bud.

midgut - The middle of the three part/division ([index/F.htm#foregut foregut] - midgut - [index/H.htm#hindgut hindgut]) of the early forming gastrointestinal tract. The midgut is initially connected on the ventral embryo surface to the external yolk sac by a yolk stalk, a narrow tubular connection. The midgut forms all the tract from beneath the stomach (duodenum, small intestine and large intestine) to the distral transverse colon. The midgut develops as an external loop "herniated" ventrally, until early fetal growth of the body wall recaptures this external loop, which also undergoes a rotation about the superior mesenteric artery to establish the adult anatomical position.

Mullerian Duct - (paramesonephric duct) An embryonic paired duct system that will form the epithelial lining of female reproductive organs: utererine tube, [U.htm#uterus uterus], upper vaginal canal. This duct system degenerate in male gonadal development. Named after Johannes Peter Muller (1801-1858) a German scientist.

Johannes Peter Müllerian - Johannes Peter Muller (1801 - 1858) in 1830 was the first to describe the duct named after him, the "Mullerian duct" also called the paramesonephric duct.

Mullerian Inhibiting Substance - (MIS, Anti-Mullerian Hormone, AMH, Mullerian inhibiting hormone, MIH). A sertoli cell secreted glycoprotein (transforming growth factor-beta, TGF-beta superfamily) that regulates gonadal and genital tract development. The main role is to inhibit paramesonephric (Mullerian) duct development in males. Postnatally, after puberty it is also expressed in females by ovarian granulosa cells and has a role in follicle development. (More? OMIM - AMH)

oviduct - (uterine horn, fallopian tube, oviduct, salpinx) see uterine tube. A pair of tubular structures designed to transport the oocyte (egg) from the ovary to the uterus body.

paramesonephric duct - (Mullerian duct) (Greek, para = "beside") The paired ducts that lie beside the mesonephric ducts, that will differentiate in the female embryo to form the female internal genital tract (uterine tubes, uterus, upper vaginal canal).

parietal pleura - Serous membrane which forms the outer lining of pleural cavity. Mesoderm of the thoracic cavity body wall and derived from epithelia of pericardioperitoneal canals from intraembryonic coelom. The inner pleural layer, visceral pleura, is splanchnic mesoderm in origin.

peritoneal cavity - The anatomical body cavity in which the lower body organs lie: intestines, liver, bladder, uterus, ovary. The peritoneal cavity forms initially from two separate regions of the early intraembryonic coelom (formed in the lateral plate mesoderm), which with embryo folding, fuse to form a single cavity. Note the single intraembryonic coelom forms all three major body cavities: pericardial, pleural, peritoneal.

Pouch of Douglas - (rectouterine pouch or rectovaginal) A female anatomical region describing the portion of the peritoneal cavity lying between the back wall of the uterus and rectum.

preantral follicle - (primary follicle]) Term used to describe the developmental stage of ovarian follicle development following primordial in describing the sequence (primordial, preantral, antral) of follicle development within the ovary. In humans, a number of primordial follicles will begin to develop into preantral follicles (primary), some of which will then form antral follicles (secondary), with only a single antral follicle developing into the ovulating follicle (Graafian) each menstrual cycle.

processus vaginalis - A transient communicating channel in testes development between tunica vaginalis and peritoneal cavity.

progesterone - A steroidal hormone of the progestogens class, which has many roles in the female. Functions include regulation of the menstrual cycle, uterine changes, maintaining pregnancy and effects on systems throughout the body. Biological sources include: adrenal glands, gonads (corpus luteum), brain, and placenta. Male progesterone has a suggested role in neural development. Progesterone is also used clinically as a part of hormone replacement therapy (HRT) in women. The human progesterone receptor has two isoforms (PRA and PRB). (More? Menstrual Cycle)

progestins - these compounds are synthetically produced progestogens used clinically and experimentally. (More? Menstrual Cycle)

prolactin - (PRL) anterior pituitary hormone which stimulates breast development and milk production in pregnancy. Also has a role in regulating follicle stimulating hormone (FSH) effect on the ovary. Protein hormone is similar in structure to both growth hormone (anterior pituitary) and chorionic somatomammotropin (placenta). Anterior pituitary release of prolactin is in turn regulated by the hypothalamus [#prolactin-releasing_hormone prolactin-releasing hormone] (PRLH, prolactin-releasing peptide). Recently been shown to to mimic in pregnancy effects of increased maternal myelination processes (oligodendrocyte precursor proliferation). (More? OMIM - PRL)

prolactin-releasing hormone - (PRLH, prolactin-releasing peptide, PRRP) an 87 amino acid peptide hypothalamus hormone which regulates anterior pituitary release of prolactin. (More? OMIM - PRLH)

puberty - (Latin, pubertas = adulthood) process involving maturation of the reproductive system. A complex process, initiated by an unknown mechanism, but involving the brain driving the hormonal axis.

rectouterine pouch - (Pouch of Douglas or rectovaginal) Anatomical description of the female peritoneal cavity lying between the back wall of the [U.htm#uterus uterus] and rectum.

renal - (Latin, renes = kidney) Term used in relation to the kidney and associated structures (renal pelvis, renal artery)

rete ovarii - A group of epithelial tubules located at the hilum of the ovary possibly mesonephric origin.

second trimester - Clinical term used to describe and divide human pregnancy period (9 months) into three equal parts of approximately three calendar months. The first trimester corresponds approximately to embryonic development (week 1 to 8) of organogenesis and early fetal. The second and third trimester correspond to the fetal period of growth in size (second trimester) and weight (third trimester), as well as continued differentiation of existing organs and tissues.

sry - (Sry, human; Testis-Determining Factor, TDF; Testis-Determining Factor on Y, TDY ) Gene name sex-determining region of Y, the gene locus on the Y chromosome encoding the male "testis determining factor", a protein transcription factor and a member of the high mobility group (HMG)-box family of DNA binding proteins. See also the transcription factor SRY-related protein, SOX9 (SRY-related high-mobility group (HMG) box 9) (More? OMIM)

stromal cells - (Greek, stroma = "a cover, table-cloth, bedding") Descriptive term in the ovary, for cells surrounding the developing follicle that form a connective tissue sheath (theca folliculi). This layer then differentiates into 2 layers (theca interna, theca externa). This region is vascularized and involved in hormone secretion.

testis-determining factor - (TDF, Sry, Testis-Determining Factor on Y, TDY ) Protein name for the protein transcription factor product of the Sry gene on the Y chromosome responsible for maleness. This protein is a member of the high mobility group (HMG)-box family of DNA binding proteins. See also the transcription factor SRY-related protein, SOX9 (SRY-related high-mobility group (HMG) box 9) (More? OMIM)

theca externa - (Greek, thek = box) The ovarian follicle stromal cells forming the outer layer of the theca folliculi surrounding the developing follicle within the ovary. Consisting of connective tissue cells, smooth muscle and collagen fibers.

theca interna - (Greek, thek >= box) The ovarian follicle endocrine cells forming the inner layer of the theca folliculi surrounding the developing follicle within the ovary. This vascularized layer of cells respond to leutenizing hormone (LH) synthesizing and secreting androgens (androstendione) transported to glomerulosa cells which process initially into testosterone and then by aromatase into estrogen (estradiol). Theca cells do not begin hormonal functions until puberty.

third trimester - Clinical term used to describe and divide human pregnancy period (9 months) into three equal parts of approximately three calendar months. The third trimester corresponds to the fetal period of growth in weight, as well as continued differentiation of existing organs and tissues. The respiratory system matures late in teh third trimester. The first trimester corresponds approximately to embryonic development (week 1 to 8) of organogenesis and early fetal period, the second trimester is the fetal period of growth in size.

trimegestone - A synthetic progesterone potentially used in postmenopausal women (with an intact [index/U.htm#uterus uterus]) in combination with estrogen as hormone-replacement therapy (HRT). (Other Progestins: levonorgestrel, 3-keto-desogestrel, dienogest, drospirenone, Nestorone and nomegestrol acetate ) Note that Trimegestone and Nestorone are currently the most potent fourth-generation progestins with no androgenic or estrogenic actions.

trimester - Clinical term used to describe and divide human pregnancy period (9 months) into three equal parts of approximately three calendar months. The first trimester corresponds approximately to embryonic development (week 1 to 8) of organogenesis and early fetal. The second and third trimester correspond to the fetal period of growth in size (second trimester) and weight (third trimester), as well as continued differentiation of existing organs and tissues.

tubulogenesis - Term used to describe the development of branched tubes from an initially unbranched epithelial bud. A fundamental process in the development of many organ systems (pancreas, mammary gland, lung, and kidney).

tunica albuginea - A dense connective tissue layer lying between germinal epithelium and cortical region of female ovary, or the equivilaent capsule of the male testis.

ultrasound - A noninvasive technique for visualizing and prenatal diagnosis of several features of development including: follicles in the ovaries, the gestational sac, fetus in the [U.htm#uterus uterus], fetal parameters, and the placenta. Uses high-frequency sound waves that are reflected off internal structures. These reflections can be analysed and displayed by computer.

ureter - The ureters are hollow tubes that link and carry urine from each kidney to the bladder. The tubes have a muscular wall lined with transitional epithelium.

urethra - The single muscular tube that links and carries urine from the bladder to the exterior. In humans, the urethral length differs between the sexes (male longer, female shorter).

urinary - Term used to describe all components of the kidney system including the bladder, ureters and urethra.

urine - Term used to describe the liquid waste produced by the kidney, stored in the bladder and excreted from the body through the urethra.

urorectal septum - (URS) The structure which develops to separate the cloaca (common urogenital sinus) into an anterior urinary part and a posterior rectal part.

URSMS - An acronym for urorectal septum malformation sequence, clinically describing abnormalities of the urorectal septum (URS) and urogenital organs.

urinary bladder - muscular sac for the storage of urine.

uterine horn - (fallopian tube, oviduct, salpinx) see uterine tube.

uterine peristalsis - rhythmic muscular contraction of the [#uterus uterus] which occurs during the menstrual cycle, maximally just before ovulation, in the non-pregnant uterus.

uterine tube - (uterine horn, oviduct, fallopian tube, salpinx) A pair of tubular structures that transport the oocyte (egg) from the ovary to the [#uterus uterus] body. They are located laterally on the upper uterus and consist medial to lateral of three main parts: isthmus (medial constricted third), ampulla (intermediate dilated portion) and infundibulum (containing the abdominal opening/ostium, surrounded by finger-like fimbriæ). The tube has structurally several layers: a lining mucosa (mix of ciliated and secretory epithelium), a middle muscularis layer (inner circular muscle layer and an outer longitudinal layer) and outer serous layer (peritoneal).

uterus - The female internal genital (reproductive) tract forming a hollow muscular walled organ, embryonically derived from the [P.htm#paramesonephric paramesonephric ducts]. The human uterus has two uterine tubes (fallopian tubes, oviducts) where the first week of development occurs and a single hollow body where implantation of the blastocyst normally occurs. Following puberty, the non-pregnant uterus (epithelium and underlying stroma) undergoes cyclic changes under the influence of hormones, the menstrual cycle. This cycle of uterine changes ceases during pregnancy. In other species females of non-primate vertebrates (eg rats, mice, horses, pig) have a reproductive cycle called the estrous cycle (oestrous, British spelling). In pregnancy, the uterus contributes the maternal component of the placenta.

villi - Plural of villus, which is a thin projection from a surface.

vitelline duct - (yolk stalk) Is a narrow endodermal channel between the yolk sac and the developing mid-gut. An abnormality associated with this duct failing to regress is called Meckel's diverticulum.

Wolffian duct - (= mesonephric duct, preferred terminology), A developmental duct that runs from the mesonephros to cloaca. The duct in male differentiates to form the vas deferens and in female regresses. Named after Caspar Friedrich Wolff (1733-1794), a German scientist and early embryology researcher and is said to have established the doctrine of germ layers.

X chromosome - The female sex chromosome, which following sexual reproduction is inherited from each parent in females, and inherited from the mother in males. This inheritence pattern impacts upon the pattern of genetic disease.

Xist - The name for a non-translated RNA (18 Kb) that is associated with the inactivated X chromosome in female cells to correct for the double gene dosage, 2 copies of teh X chromosome.

X inactivation - Process that occurs in all cells within females, each cell has 2 copies of the X chromosome (one from father and one from mother) one of copy of which is randomly inactivated throughout the entire body in order to maintain gene dosage.

X linked - Term used to refer to genes, and genetic diseases, located on the X chromosome. Therefore more likely to be expressed in males, where there is only a single maternal X chromosome.

yolk sac - An [index/E.htm#extraembryonic_membrane extraembryonic membrane]which is endoderm origin and covered with extraembryonic mesoderm. Yolk sac lies outside the embryo connected initially by a yolk stalk to the midgut with which it is continuous with. The endodermal lining is continuous with the endoderm of the gastrointestinal tract. In reptiles and birds, the yolk sac has a function associated with nutrition. In mammals the yolk sac acts as a source of primordial germ cells and blood cells. (More 2010-04-12T17:17:11Search Google