Uterus Development

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Paramesonephric ducts.jpg

Introduction

Johannes Müller (1801 - 1858)
Human fetal uterus growth

This page introduces the uterus as part of the internal female reproductive tract development. Two paramesonephric ducts form from coelomic epithelium extending beside the mesonephric ducts. In the absence of Mullerian Inhibitory Factor these ducts proliferate and grow extending from the vaginal plate on the wall of the urogenital sinus to lie beside the developing ovary. The paired ducts begin to fuse from the vaginal plate end, forming the primordial body of the uterus and the unfused lateral arms form the uterine tubes. Recent research points to the paramesonephric ducts also being the entire embryonic origin of the vagina.


Johannes Peter Müller (1801 - 1858) in 1830 was the first to describe the duct historically named after him, the "Müllerian duct". The current terminology is the "paramesonephric duct".


For the pregnant uterus see Implantation and Maternal Decidua.

Genital Links: genital | Lecture - Medicine | Lecture - Science | Lecture Movie | Medicine - Practical | primordial germ cell | meiosis | Female | X | ovary | oocyte | uterus | vagina | reproductive cycles | menstrual cycle | Male | Y | testis | spermatozoa | penis | prostate | endocrine gonad‎ | Genital Movies | genital abnormalities | Assisted Reproductive Technology | puberty | Category:Genital
Historic Embryology - Genital 
1901 Urinogenital Tract | 1902 The Uro-Genital System | 1904 Ovary and Testis | 1904 Leydig Cells | 1904 Hymen | 1905 Testis vascular | 1909 Prostate | 1912 Prostate | 1912 Urinogenital Organ Development | 1914 External Genitalia | 1914 Female | 1915 Cowper’s and Bartholin’s Glands | 1920 Wolffian tubules | 1921 Urogenital Development | 1921 External Genital | 1927 Female Foetus 15 cm | 1932 Postnatal Ovary | 1935 Prepuce | 1935 Wolffian Duct | 1942 Sex Cords | 1943 Testes Descent | 1953 Germ Cells | Historic Embryology Papers | Historic Disclaimer


Menstrual Cycle Links: Introduction | Menstrual Cycle - Histology | ovary | oocyte | uterus | Uterine Gland | estrous cycle | pregnancy test
Historic Embryology - Menstrual 
1851 Corpus Luteum | 1933 Pap Smear | 1942 Human Reproduction Hormones | 1951 Corpus Luteum

Implantation | Maternal Decidua | Category:Uterus

Some Recent Findings

  • Review - The cell biology and molecular genetics of Müllerian duct development[1] "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)."
  • Outcome of assisted reproduction in women with congenital uterine anomalies: a prospective observational study[2] "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. ...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."
  • WNT4 coordinates directional cell migration and extension of the Müllerian duct essential for ontogenesis of the female reproductive tract[3] "The Müllerian duct (MD) is the anlage of the oviduct, uterus and upper part of the vagina, the main parts of the female reproductive tract. Several wingless-type mouse mammary tumor virus (MMTV) integration site family member (Wnt) genes, including Wnt4, Wnt5a and Wnt7a, are involved in the development of MD and its derivatives, with Wnt4 particularly critical, since the MD fails to develop in its absence. We use, here, Wnt4(EGFPCre)-based fate mapping to demonstrate that the MD tip cells and the subsequent MD cells are derived from Wnt4+ lineage cells. Moreover, Wnt4 is required for the initiation of MD-forming cell migration." WNT4
  • LHX1 is required in Müllerian duct epithelium for uterine development[4] "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." HGNC
More recent papers  
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: Uterus Development

Veronika Aleksandrovych, Magdalena Białas, Artur Pasternak, Tomasz Bereza, Marek Sajewicz, Jerzy Walocha, Krzysztof Gil Identification of uterine telocytes and their architecture in leiomyoma. Folia Med Cracov: 2018, 58(3);89-102 PubMed 30521514

Susanta K Behura, Andrew M Kelleher, Thomas E Spencer Evidence for functional interactions between the placenta and brain in pregnant mice. FASEB J.: 2018;fj201802037R PubMed 30521381

Brendan Backhouse, Chloe Hanna, Gorjana Robevska, Jocelyn van den Bergen, Emanuele Pelosi, Cas Simons, Peter Koopman, A Zulfa Juniarto, Sonia Grover, Sultana Faradz, Andrew Sinclair, Katie Ayers, Tiong Y Tan Identification of Candidate Genes for Mayer-Rokitansky-Küster-Hauser Syndrome Using Genomic Approaches. Sex Dev: 2018; PubMed 30504698

Tetsuya Okaneya, Kiyoshi Onishi, Michio Saze, Kei Iwakura, Hiroko Sakuma A Case of Clitoral Hypertrophy of Unknown Origin. Case Rep Obstet Gynecol: 2018, 2018;7865832 PubMed 30515338

Ka Ying Bonnie Ng, Susan Wellstead, Ying Cheong, Nick Macklon A randomised controlled trial of a personalised lifestyle coaching application in modifying periconceptional behaviours in women suffering from reproductive failures (iPLAN trial). BMC Womens Health: 2018, 18(1);196 PubMed 30514285

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • The origin of the Mullerian duct in chick and mouse[5] "In vertebrates the female reproductive tracts derive from a pair of tubular structures called Mullerian ducts, which are composed of three elements: a canalised epithelial tube, mesenchymal cells surrounding the tube and, most externally, coelomic epithelial cells. ... We show that all Mullerian duct components derive from the coelomic epithelium in both species. Our data support a model of a Mullerian epithelial tube derived from an epithelial anlage at the mesonephros anterior end, which then segregates from the epithelium and extends caudal of its own accord, via a process involving rapid cell proliferation. This tube is surrounded by mesenchymal cells derived from local delamination of coelomic epithelium."
  • Essential roles of mesenchyme-derived beta-catenin in mouse Mullerian duct morphogenesis[6]

Paramesonephric Duct

The Müllerian duct (= paramesonephric duct, preferred terminology) paired ducts that form the epithelial lining of female reproductive organs: utererine tube, uterus, upper vaginal canal. The term "paramesonephric" duct means beside the mesonephric (Wolffian) duct, which is its anatomical location in early development. Mullerian refers to Johannes Peter Müller (1801-1858) a German scientist who specialised in comparative anatomy. These ducts initially form and then degenerate in the male.

A recent study using both chicken and mouse embryos has shown that these initially paired tubular structures derive from the coelomic epithelium.[5]

"Müllerian epithelial tube derived from an epithelial anlage at the mesonephros anterior end, which then segregates from the epithelium and extends caudal of its own accord, via a process involving rapid cell proliferation. This tube is surrounded by mesenchymal cells derived from local delamination of coelomic epithelium."

Mullerian ducts have three elements:

  1. a canalised epithelial tube
  2. mesenchymal cells surrounding the tube
  3. coelomic epithelial cells


Duct Molecular Development

The paired paramesonephic ducts (Müllerian ducts) go through a series of developmental changes recently identified as regulated by a number of molecular factors.

Initiation

Coelomic epithelium Lim1 expressing cells are specified to a duct fate.[7]

  • Lim - proteins named for 'LIN11, ISL1, and MEC3,' are defined by the possession of a highly conserved double zinc finger motif called the LIM domain.
    • LIM domain-binding factors - interact with the LIM domains of nuclear proteins are capable of binding to a variety of transcription factors.

Invagination

  • Wnt4 - induces duct invagination to reach the mesonephric (Wolffian)

Elongation

  • WNT9b - from mesonephric duct to guide paramesonephric duct elongation. Cysteine-rich secreted glycoprotein.
  • Pax2 - also acts in elongation and duct maintenance. Member of the paired box protein family.

Cells at the leading tip proliferate and form the duct elongating to reach the cloaca (urogenital sinus).



Links: OMIM - WNT9b | OMIM - Pax2 | OMIM - paired box gene


Uterine Development Movie

Anterior view of development of the female uterus and vagina between Week 9 and 20.

The paramesonephric ducts (red) fuse in the midline to form the genital canal.

The urogenital sinus (yellow), in contact with the paramesonephric duct, thickens to form the sinusal tubercle which extends as a solid vaginal plate, then becomes hollow as the sinovaginal bulb, finally forming the vagina.


Development Overview

Urogenital indifferent.jpg Urogenital female.jpg
Common
Female
Internal Genital Tract Differentiation
Mullerian Duct (paramesonephric) - blue
(This historic image mislabels the vaginal origin)

The data below gives an overview of the timecourse of embryonic human uterine development.[8]

Carnegie stage 18 - Mullerian duct to the coelomic cavity was formed as the result of an invagination of the coelomic epithelium - stage 18
Carnegie stages 19 - 23 - duct grows independently from the invagination - stage 19
Week 20 - uterine horn fimbrial development begins and continues after birth - second trimester


Fetal Uterus

Paramesonephric ducts.jpg Paramesonephric duct.jpg
Urogenital sinus of female human embryo of eight and a half to nine weeks old (From model by Keibel) (Image: Gray's Anatomy) (Image modified from: Drews U, Sulak O, Schenck PA. Androgens and the development of the vagina.Biol Reprod. 2002 Oct;67(4):1353-9. PMID: 12297555)

Fetal Uterus Growth

Fetal uterus growth.jpg
Graph shows the growth during the fetal period of the uterus between week 19 and 38.[9] During this time the uterine circumferunce increases from about 20 mm to just under 60mm and the width increases from less than 10mm to just over 20 mm.

Uterine horn fimbrial development begins after week 20 and continues after birth.

Uterine growth continues postnatally, increasing outer muscle thickness and cyclic changes in the lining with puberty.

Adult external uterine orifice to the fundus is approximately 6.25 cm.

Newborn Uterus

Newborn uterus.jpg

Growth of the Uterus in the Postfetal Period
Age Length of corpus (mm) Length of isthmus (mm) Length of cervix (mm) Total length (mm)
Fetus of 7 months 22
Child of 5 weeks 27
1 year 10 23
14 months 10 5 12 27
2.5 years 8 6 12 26
3 years 9-10 5-6 10 25
3.5 years 6 5 16 27
9 years 9 4.5 13 27
11 years 12 6 19 37
13 years 27 56
15 years 59
16 years 41 12 25 78
17 years 27 6 22 55
17 years 20 4 16 40
18 years 36 5 31 72
19 years 27 5 28 60
19 years 28 6 27 61
19 years 24 8 21 53
20 years 30 6 16 52
20 years 30 7 21 58
22 years 35 5 29 69
28 years 40 10 28 78
29 years (nulliparous wife) 34 10 34 78
30 years (virgin) 38 7 29 74
    Data compiled from Hegar (1908) | Uterus Growth Table | Collapsible Table | Uterus Development

Uterine Tubes

Adult Human right uterine tube and ovary
Developing Uterus (cat) showing relationship to ovary and degenerating mesonephros.

The unfused portion of the paramesonephric ducts will form the uterine tubes. Note that there are several synonyms used for the paired uterine tubes or Fallopian tubes or oviducts or uterine horns.

In the adult, the uterine tube has been described in 4 anatomical regions.

Week1 001 icon.jpg
infundibulum ampulla isthmus intramural
funnel-shaped (up to 10 mm in diameter) end of the oviduct. Finger-like extensions of its margins, the fimbriae, are closely applied to the ovary. Ciliated cells are frequent. mucosal folds, or plicae, and secondary folds which arise from the plicae divide the lumen of the ampulla into a very complex shape. Fertilization usually takes place in the ampulla. narrowest portion (2-3 mm in diameter) of the tube located in the peritoneal cavity. Mucosal folds are less complex and the muscularis is thick. An inner, longitudinal layer of muscle is present in the isthmus. penetrates the wall of the uterus. The mucosa is smooth, and the inner diameter of the duct is very small.


Mucosa

  • formed by a ciliated and secretory epithelium resting on a very cellular lamina propria.
  • The number of ciliated cells and non-ciliated secretory cells varies along the oviduct.
  • Secretory activity varies during the menstrual cycle, and resting secretory cells are also referred to as peg-cells.
  • Some of the secreted substances are thought to nourish the oocyte and the very early embryo.

Muscularis

  • inner circular muscle layer and an outer longitudinal layer.
  • An inner longitudinal layer is present in the isthmus and the intramural part of the oviduct.
  • Peristaltic muscle action seems to be more important for the transport of sperm and oocyte than the action of the cilia.

Uterine Blood Supply

Gray1170.jpg


Uterine Glands

Uterine Gland Secretory Phase histology
Uterine Gland Secretory Phase

Uterine adenogenesis is the term used to describe the formation of uterine glands from the epithelial lining of the uterus that begins prenatal in humans. In other species, the overt development occurs postnatally and has been described through a 3 step the sequence:

  1. differentiation and budding of the glandular epithelium.
  2. invagination and tubular coiling of the epithelium.
  3. branching of the glandular elements and their expansion throughout the endometrial stroma toward the myometrium.

Epithelial-mesenchymal interaction occurs through Wnt signalling during this process:

  • Wnt7a - expressed in the luminal epithelium
  • Wnt5a - expressed in the mesenchyme

In mice, this development sequence occurs between postnatal day (PND) 5 to 7 and involves Wnt up-regulation of Lymphoid Enhancing Factor 1 (Lef1).[10]

Postnatally both prolactin and estradiol-17 beta (and their receptors) regulate gland development. There are some gland species gestational differences, in both sheep and pigs the glands provide additional histotrophic support by undergoing extensive hyperplasia and hypertrophy.[11]

Links: Wnt | Epithelial Mesenchymal Interaction

Postnatal Growth

Growth of the Uterus in the Postfetal Period
Age Length of corpus (mm) Length of isthmus (mm) Length of cervix (mm) Total length (mm)
Fetus of 7 months 22
Child of 5 weeks 27
1 year 10 23
14 months 10 5 12 27
2.5 years 8 6 12 26
3 years 9-10 5-6 10 25
3.5 years 6 5 16 27
9 years 9 4.5 13 27
11 years 12 6 19 37
13 years 27 56
15 years 59
16 years 41 12 25 78
17 years 27 6 22 55
17 years 20 4 16 40
18 years 36 5 31 72
19 years 27 5 28 60
19 years 28 6 27 61
19 years 24 8 21 53
20 years 30 6 16 52
20 years 30 7 21 58
22 years 35 5 29 69
28 years 40 10 28 78
29 years (nulliparous wife) 34 10 34 78
30 years (virgin) 38 7 29 74
  Data compiled from: Hegar K. Anatomical investigations on the nullipara uterus with special consideration of isthmus (Anatomische Untersuchungen am nullipara Uterus mit besonderer Berücksichtigung der Isthmus). (1908) Beitraae zur Geburtsh. u. Gynak., vol. 13, 1908. reference list | Uterus Growth Table | Collapsible Table | Uterus Development

Uterus Histology

See also Menstrual Cycle - Histology

Abnormalities

Uterine didelphys, obstructed hemivagina, and ectopic ureter on MR imaging in a 17-year-old girl.[12]


There are at least two clinical society classifications for female genital tract abnormalities:

  1. European Society of Human Reproduction and Embryology—European Society for Gynaecological Endoscopy (ESHRE-ESGE)[13]
  2. American Society for Reproductive Medicine (ASRM) [14]

ESHRE-ESGE Classification

European Society for Gynaecological Endoscopy (ESHRE-ESGE)[13]

Uterine anatomical deviations deriving from the same embryological origin:

  • U0 - normal uterus
  • U1 - dysmorphic uterus
  • U2 - septet 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.


ESHRE/ESGE Classification of Uterine Anomalies  
European Society of Human Reproduction and Embryology (ESHRE) and the European Society for Gynaecological Endoscopy (ESGE)
  • Class U0 - incorporates all cases with normal uterus.
  • Class U1 - (Dysmorphic uterus) incorporates all cases with normal uterine outline but with an abnormal shape of the uterine cavity excluding septa. Class I is further subdivided into three categories
    • Class U1a - (T-shaped uterus) characterized by a narrow uterine cavity due to thickened lateral walls with a correlation 2/3 uterine corpus and 1/3 cervix,
    • Class U1b - (uterus infantilis) characterized also by a narrow uterine cavity without lateral wall thickening and an inverse correlation of 1/3 uterine body and 2/3 cervix
    • Class U1c - (others) which is added to include all minor deformities of the uterine cavity including those with an inner indentation at the fundal midline level of less than 50 % of the uterine wall thickness.
  • Class U2 - (septate uterus) internal indentation >50 % of the uterine wall thickness & external contour straight or with indentation <50 %
    • Class U2a - (partial septate uterus) characterized by the existence of a septum dividing partly the uterine cavity above the level of the internal cervical os
    • Class U2b - (complete septate uterus) characterized by the existence of a septum fully dividing the uterine cavity up to the level of the internal cervical os.
  • Class U3 - (bicorporeal uterus) external indentation >50 % of the uterine wall thickness
    • Class U3a - (partial bicorporeal uterus) characterized by an external fundal indentation partly dividing the uterine corpus above the level of the cervix
    • Class U3b - (complete bicorporeal uterus) width of the fundal indentation at the midline >150 % of the uterine wall thickness) completely dividing the uterine corpus up to the level of the cervix
    • Class U3c - (bicorporeal septate uterus) characterized by the presence of an absorption defect in addition to the main fusion defect.
  • Class U4 - (hemi-uterus) incorporates all cases of unilateral formed uterus. Hemi-uterus is defined as the unilateral uterine development; the contralateral part could be either incompletely formed or absent.
    • Class U4a - (hemi-uterus with a rudimentary (functional) cavity) characterized by the presence of a communicating or non-communicating functional contralateral horn
    • Class U4b - (hemi-uterus without rudimentary (functional) cavity) characterized either by the presence of non-functional contralateral uterine horn or by aplasia of the contralateral part.
  • Class U5 - (aplastic uterus) incorporates all cases of uterine aplasia, formation defect characterized by the absence of any fully or unilaterally developed uterine cavity.
    • Class U5a - (aplastic uterus with rudimentary (functional) cavity) characterized by the presence of bi- or unilateral functional horn
    • Class U5b - (aplastic uterus without rudimentary (functional) cavity) characterized either by the presence of uterine remnants or by full uterine aplasia.
  • Class U6 - is kept for still unclassified cases.
Uterine anomalies ESHRE-ESGE classification

Grigoris F Grimbizis, Stephan Gordts, Attilio Di Spiezio Sardo, Sara Brucker, Carlo De Angelis, Marco Gergolet, Tin-Chiu Li, Vasilios Tanos, Hans Brölmann, Luca Gianaroli, Rudi Campo The ESHRE-ESGE consensus on the classification of female genital tract congenital anomalies. Gynecol Surg: 2013, 10(3);199-212 PubMed 23894234


See also ICD10 Congenital malformations of genital organs (Q50-Q56)

Links: Genital System - Abnormalities | Uterus Development | image - simplified cartoon

Uterine anomalies ESHRE-ESGE classification

Uterine Duplication

Uterine abnormalities.jpg A range of uterine and vaginal anatomical anomalies based upon the abnormal development and fusion of the paramesonephric ducts and vaginal plate development.

 

Unicornate uterus.jpg Unicornate Uterus - failure of the paramesonephric ducts to fuse. A single paramesomnephric duct has fused with the vaginal plate and now opens into the vagina, while the other forms a diverticulum.
Bicornuate uterus ectopic movie icon.jpg
 ‎‎Bicornuate Ectopic
Page | Play

Bicornuate uterus01.jpg

Bicornuate uterus containing conceptus chorionic sac with placental cord on one side.

Septate Uterus

Uterine residual septum classification:

  1. American Society for Reproductive Medicine (ASRM) criterion with an internal fundal indentation length equal or greater than 1 cm[15]
  2. European Society of Human Reproduction and Embryology—European Society for Gynaecological Endoscopy (ESHRE-ESGE) classification of female genital tract congenital anomalies with an internal indentation at the fundal midline greater than 50% myometrial thickness.[13]

Septate uterus ultrasound

Septate Uterus Ultrasound[16]

Uterine Duplication

(uterus didelphys, double uterus, uterus didelphis) A rare uterine developmental abnormality where the paramesonephric ducts (Mullerian ducts) completely fail to fuse generating two separate uterus parts each connected to the cervix and having an ovary each.


Uterus/Vaginal

Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH, MRK anomaly, Rokitansky-Kuster-Hauser syndrome, RKH syndrome, RKH) consists of congenital aplasia of the uterus and the upper part of vagina due to anomalous development of Müllerian ducts, either isolated or associated with other congenital malformations, including renal, skeletal, hearing and heart defects. Has an incidence of approximately 1 in 4500 newborn girls and has been associated with a microdeletion at 17q12.[17]


Cervical: cervical agenesis, cervical duplication


Environmental Abnormalities

DES Diethylstilbestrol or diethylstilbetrol, is a drug that was prescribed to women from 1938-1971 to prevent miscarriage in high-risk pregnancies. The drug acted as a potent estrogen (mimics natural hormone) and therefore could also act as a potential endocrine disruptor. This led to a number of developing fetal reproductive tract and other abnormalities. In the female fetus, it increased risk of abnormal reproductive tract and also carcinogenic (cancer forming). In the male fetus, it increased the occurance of abnormal genitalia. The drug was banned by FDA (USA) in 1979 as a teratogen, it had previously also been used as livestock growth promoter and could have potentially entered the human food chain. (More? [endocrine2.htm Endocrine Abnormalities] | Abnormal Development - Drugs)


Links: Endocrine Abnormalities | Abnormal Development - Drugs | Childrens Hospital Boston - Congenital Anomalies of the Uterus | Medical Education Image Link - Cervical agenesis | OMIM - Rokitansky-Kuster-Hauser syndrome |

Cervical Cancer

In Australia, the "Pap Smear" test was replaced in 2017 (1 December) by a new "National Cervical Screening Program". This new program will use new technologies to detect HPV DNA rather than pathological screening for abnormal cells from a "Pap Smear". For more information see the external links below.

DOH Information Video

Australian Department of Health (Published on Nov 1, 2017)

"The two yearly Pap test for women aged 18 to 69 will change to a five yearly human papillomavirus (HPV) test for women aged 25 to 74. Women will be due for the first Cervical Screening Test two years after their last Pap test."


"The Cervical Screening Test detects infection with human papillomavirus (HPV). Partial genotyping is used to determine the type of HPV into one of two groups: oncogenic HPV 16/18 or oncogenic HPV types other than 16/18 as a pooled result." (NCSP Factsheet)


Links: National Cervical Screening Program | Factsheet | Compass Trial |

ABC radio program Monday 27 March 2017 - Death of the pap smear? | ABC Audio - Death of the pap smear?

History of the Pap Smear

The information below relates to the original "Pap Smear" (Papanicolaou smear, pap test, cervical smear) The text below is from the ABC - Great Moments In Science.

"Luckily, we have the famous Pap Smear - an excellent way to find cancer of the cervix before it digs in locally and/or spreads throughout the body. The Pap Smear is named after a certain Dr. Papanicolaou - who did a Pap Smear on his wife virtually every day for 20 years.
George Nikolas Papanicolaou was born in 1883 in Kymi, a small town overlooking the Aegean Sea on the Island of Euboea in Greece. His father, Nikolas Papanicolaou was both the Major of Kymi and a medical doctor. His older brother, Naso, had studied law, so his father convinced George to continue in the family medical tradition. So George studied medicine, and did well, graduating with a degree in honours in 1904............"


Links: Menstrual Cycle - Histology | Dilatation and curettage (D&C) | ABC - Great Moments In Science


Broad Ligament

The broad ligament is found associated with the internal human female genital tract. It forms a mesentery consisting of a double fold of the peritoneum that connects the uterus to the peritoneal floor and walls.

Anatomically it has three parts:

  1. mesometrium - surrounding the uterus
  2. mesosalpinx - surrounding the uterine tube
  3. mesovarium - surrounding the ovary

Abnormalities include peritoneal endometriosis.

Gray1161.jpg

Molecular

Wnt genes - Wnt4, Wnt5a, and Wnt7a implicated in the formation and morphogenesis of the Müllerian duct.

Wnt7a - mediates the patterning of the oviduct and differentiation of the uterus.

beta-catenin - manufactured in the mesenchyme is a downstream effector of Wnt7a.

Bmp2 - decidualization regulator of gene expression and function (shown in mouse uterus).

Lim1, Lhx9, Emx, Pax-2, Hox-A9, Hox-A10, Hox-A11, Hox-A13, WT1, SF-1, GATA-4. TGF-beta


References

  1. Roly ZY, Backhouse B, Cutting A, Tan TY, Sinclair AH, Ayers KL, Major AT & Smith CA. (2018). The cell biology and molecular genetics of Müllerian duct development. Wiley Interdiscip Rev Dev Biol , , . PMID: 29350886 DOI.
  2. Prior M, Richardson A, Asif S, Polanski L, Parris-Larkin M, Chandler J, Fogg L, Jassal P, Thornton JG & Raine-Fenning NJ. (2018). Outcome of assisted reproduction in women with congenital uterine anomalies: a prospective observational study. Ultrasound Obstet Gynecol , 51, 110-117. PMID: 29055072 DOI.
  3. Prunskaite-Hyyryläinen R, Skovorodkin I, Xu Q, Miinalainen I, Shan J & Vainio SJ. (2016). Wnt4 coordinates directional cell migration and extension of the Müllerian duct essential for ontogenesis of the female reproductive tract. Hum. Mol. Genet. , 25, 1059-73. PMID: 26721931 DOI.
  4. Huang CC, Orvis GD, Kwan KM & Behringer RR. (2014). Lhx1 is required in Müllerian duct epithelium for uterine development. Dev. Biol. , 389, 124-36. PMID: 24560999 DOI.
  5. 5.0 5.1 Guioli S, Sekido R & Lovell-Badge R. (2007). The origin of the Mullerian duct in chick and mouse. Dev. Biol. , 302, 389-98. PMID: 17070514 DOI.
  6. Deutscher E & Hung-Chang Yao H. (2007). Essential roles of mesenchyme-derived beta-catenin in mouse Müllerian duct morphogenesis. Dev. Biol. , 307, 227-36. PMID: 17532316 DOI.
  7. Kobayashi A, Shawlot W, Kania A & Behringer RR. (2004). Requirement of Lim1 for female reproductive tract development. Development , 131, 539-49. PMID: 14695376 DOI.
  8. Hashimoto R. (2003). Development of the human Müllerian duct in the sexually undifferentiated stage. Anat Rec A Discov Mol Cell Evol Biol , 272, 514-9. PMID: 12740945 DOI.
  9. Soriano D, Lipitz S, Seidman DS, Maymon R, Mashiach S & Achiron R. (1999). Development of the fetal uterus between 19 and 38 weeks of gestation: in-utero ultrasonographic measurements. Hum. Reprod. , 14, 215-8. PMID: 10374123
  10. Shelton DN, Fornalik H, Neff T, Park SY, Bender D, DeGeest K, Liu X, Xie W, Meyerholz DK, Engelhardt JF & Goodheart MJ. (2012). The role of LEF1 in endometrial gland formation and carcinogenesis. PLoS ONE , 7, e40312. PMID: 22792274 DOI.
  11. Gray CA, Bartol FF, Tarleton BJ, Wiley AA, Johnson GA, Bazer FW & Spencer TE. (2001). Developmental biology of uterine glands. Biol. Reprod. , 65, 1311-23. PMID: 11673245
  12. Wang ZJ, Daldrup-Link H, Coakley FV & Yeh BM. (2010). Ectopic ureter associated with uterine didelphys and obstructed hemivagina: preoperative diagnosis by MRI. Pediatr Radiol , 40, 358-60. PMID: 19924410 DOI.
  13. 13.0 13.1 13.2 Grimbizis GF, Gordts S, Di Spiezio Sardo A, Brucker S, De Angelis C, Gergolet M, Li TC, Tanos V, Brölmann H, Gianaroli L & Campo R. (2013). The ESHRE-ESGE consensus on the classification of female genital tract congenital anomalies. Gynecol Surg , 10, 199-212. PMID: 23894234 DOI.
  14. . (1988). The American Fertility Society classifications of adnexal adhesions, distal tubal occlusion, tubal occlusion secondary to tubal ligation, tubal pregnancies, müllerian anomalies and intrauterine adhesions. Fertil. Steril. , 49, 944-55. PMID: 3371491
  15. Bermejo C, Martínez Ten P, Cantarero R, Diaz D, Pérez Pedregosa J, Barrón E, Labrador E & Ruiz López L. (2010). Three-dimensional ultrasound in the diagnosis of Müllerian duct anomalies and concordance with magnetic resonance imaging. Ultrasound Obstet Gynecol , 35, 593-601. PMID: 20052665 DOI.
  16. Ludwin A, Ludwin I, Pityński K, Banas T & Jach R. (2014). Role of morphologic characteristics of the uterine septum in the prediction and prevention of abnormal healing outcomes after hysteroscopic metroplasty. Hum. Reprod. , 29, 1420-31. PMID: 24838703 DOI.
  17. 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. (2009). Recurrent microdeletion at 17q12 as a cause of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome: two case reports. Orphanet J Rare Dis , 4, 25. PMID: 19889212 DOI.


Reviews

Farage M & Maibach H. (2006). Lifetime changes in the vulva and vagina. Arch. Gynecol. Obstet. , 273, 195-202. PMID: 16208476 DOI.

Cummings AM & Kavlock RJ. (2004). Function of sexual glands and mechanism of sex differentiation. J Toxicol Sci , 29, 167-78. PMID: 15467266

Articles

Deutscher E & Hung-Chang Yao H. (2007). Essential roles of mesenchyme-derived beta-catenin in mouse Müllerian duct morphogenesis. Dev. Biol. , 307, 227-36. PMID: 17532316 DOI.

Guioli S, Sekido R & Lovell-Badge R. (2007). The origin of the Mullerian duct in chick and mouse. Dev. Biol. , 302, 389-98. PMID: 17070514 DOI.

Hashimoto R. (2003). Development of the human Müllerian duct in the sexually undifferentiated stage. Anat Rec A Discov Mol Cell Evol Biol , 272, 514-9. PMID: 12740945 DOI.

Search PubMed

Search May 2007 "embryonic uterine development" 3,025 reference articles of which 491 were reviews.

Search Pubmed: Uterus Development | embryonic uterine development | Paramesonephric Duct | Mullerian Duct | Endocrine Disruptors | uterine+adenogenesis

Additional Images

Terms

Note some of these terms relate to the adult or the maternal uterus during pregnancy.

  • cervical cerclage - A clinical birth procedure involving circumferential banding or suture of the cervix early (between 12 -14 weeks) or when required to prevent or treat passive dilation prior to completion of pregnancy (37 weeks), described as cervical insufficiency.
  • cervical insufficiency - (CI) A clinical term describing a painless and progressive dilatation and effacement of the cervix that may lead to second trimester abortions or preterm delivery. It has also been described as inability of the uterine cervix to retain a pregnancy in the absence of uterine contractions. The condition may in some instances treated clinically by cervical cerclage. The biological basis is currently undetermined with some evidence showing a genetic relationship.
  • cervical length - There is some data that shows the risk of spontaneous preterm labour and delivery increases in women who have a short cervix PMID 8569824.
  • cervical mucus plug - (CMP) During early pregnancy, maternal glands located at the cervical junction between vagina and uterus secrete mucus that forms a plug or barrier between these two structures.
  • cervical pregnancy - A rare type of ectopic pregnancy with implantation at the cervical canal, occurring with an incidence ranging between 1:1,000 and 1:18,000 pregnancies. Clinically, when an associated haemorrhage occurs a hysterectomy is usually performed.
  • cervical ripening - Clinical birth term describing the hormonal softening of the cervix to allow expansion in preparation for birth.
  • cervix - (Latin, cervix = neck) The female anatomical region of the uterus forming a canal that opens and connects to the vagina.
  • fallopian tube obstruction - (tubal occlusion) A blockage of the uterine tube that can affect fertility due to a pathologic occlusion, spasm or plugging and also be either unilateral (single tube) or bilateral (both tubes). Described anatomically as in the proximal, the mid or the distal part of the tube.
  • fundus - (Latin, fundus = "bottom") Top part of the uterus body lying between the two uterine tubes and a common implantation site.
  • hysterosalpingography - A clinical diagnostic technique used to visualise the uterine cavity by X-ray.
  • hysteroscopy - A clinical diagnostic technique used to visualise the uterine cavity by a camera or video.
  • peg-cell - (resting secretory cell) A histological term for the non-ciliated secretory epithelial cells located within the uterus.
  • Pouch of Douglas - (rectouterine pouch or rectovaginal) Anatomical description of the female peritoneal cavity lying between the back wall of the uterus and rectum.
  • rectouterine pouch - (Pouch of Douglas or rectovaginal) Anatomical description of the female peritoneal cavity lying between the back wall of the uterus and rectum.
  • sonohysterography - A clinical diagnostic technique used to visualise the uterine cavity by ultrasound. Firstly, fluid is injected through the cervix into the uterus, then ultrasound is carried out to image the uterine cavity.


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Cite this page: Hill, M.A. (2018, December 9) Embryology Uterus Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Uterus_Development

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© Dr Mark Hill 2018, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G