Uterus Development

Embryology - 5 Dec 2023        Expand to Translate
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Introduction

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. For the pregnant uterus see implantation and maternal decidua.

Historic Embryology

Johannes Peter Müller (1801 - 1858) in 1830 was the first to describe the female genital duct that develops as the uterus and vagina, historically named after him as the "Müllerian duct". The current terminology is the "paramesonephric duct".

Genital Links: genital | Lecture - Medicine | Lecture - Science | Lecture Movie | Medicine - Practical | primordial germ cell | meiosis | endocrine gonad‎ | Genital Movies | genital abnormalities | Assisted Reproductive Technology | puberty | Category:Genital Female | X | X inactivation | ovary | corpus luteum | oocyte | uterus | vagina | reproductive cycles | menstrual cycle | Category:Female Male | Y | SRY | testis | spermatozoa | ductus deferens | penis | prostate | Category:Male

Historic Embryology - Genital  General: 1901 Urinogenital Tract | 1902 The Uro-Genital System | 1904 Ovary and Testis | 1912 Urinogenital Organ Development | 1914 External Genitalia | 1921 Urogenital Development | 1921 External Genital | 1942 Sex Cords | 1953 Germ Cells | Historic Embryology Papers | Historic Disclaimer Female: 1904 Ovary and Testis | 1904 Hymen | 1912 Urinogenital Organ Development | 1914 External Genitalia | 1914 Female | 1921 External Genital | 1927 Female Foetus 15 cm | 1927 Vagina | 1932 Postnatal Ovary Male: 1887-88 Testis | 1904 Ovary and Testis | 1904 Leydig Cells | 1906 Testis vascular | 1909 Prostate | 1912 Prostate | 1914 External Genitalia | 1915 Cowper’s and Bartholin’s Glands | 1920 Wolffian tubules | 1935 Prepuce | 1935 Wolffian Duct | 1942 Sex Cords | 1943 Testes Descent | Historic Embryology Papers | Historic Disclaimer

Category:Uterus

Some Recent Findings

Review - Müllerian duct anomalies coincident with endometriosis "The association between obstructed müllerian duct anomalies and endometriosis has been well established and the pathogenesis is attributed to the theory of retrograde menstruation. However, this relationship with endometriosis is less clear in women with unobstructed müllerian duct anomalies and in those with rudimentary uterine structures that lack functioning endometrial tissue. This article reviews the embryology, genetics, pathophysiology, and American Society for Reproductive Medicine (ASRM) classification for müllerian duct anomalies together with the genetics and pathophysiology of endometriosis to provide a framework for understanding the complex relationship between these two entities. Available published data examining the coexistence of endometriosis in relationship to müllerian duct anomalies, including studies that stratify this relationship according to specific classes of anomalies, are reviewed and organized. Awareness of the increased prevalence of endometriosis among patients with uterine anomalies, particularly those with outflow obstruction, may facilitate early diagnosis of endometriosis and subsequent intervention, with the potential to reverse disease symptoms and arrest disease progression." The histone methyltransferase EZH2 is required for normal uterine development and function in mice "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. ...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." Livebirth after uterus transplantation from a deceased donor in a recipient with uterine infertility "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. ...We describe, to our knowledge, the first case worldwide of livebirth following uterine transplantation from a deceased donor in a patient with congenital uterine absence (Mayer-Rokitansky-Küster-Hauser [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." Review - The cell biology and molecular genetics of Müllerian duct development "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 "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."

More recent papers

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link. This search now requires a manual link as the original PubMed extension has been disabled. The displayed list of references do not reflect any editorial selection of material based on content or relevance. References also appear on 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. More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Uterus Development | Uterus Embryology | Müllerian Duct | Uterine Tube Development | Cervix Development | Broad Ligament Development

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. WNT4 coordinates directional cell migration and extension of the Müllerian duct essential for ontogenesis of the female reproductive tract "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 "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 The origin of the Mullerian duct in chick and mouse "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

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.

"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.

• 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

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.

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

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

Graph shows the growth during the fetal period of the uterus between week 19 and 38. 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

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.

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 tube (monkey) histology overview

• 

  Uterine tube (monkey) epithelium and underlying histology

• 

Uterine Blood Supply

Uterine Glands

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).

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.

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

• 

  Uterine tube histology overview showing epithelium and underlying muscular layers

• 

  Uterine tube epithelium histology showing secretory and ciliated cells

• 

  Uterine body endometrium and myometrium during the proliferative phase of the menstrual cycle overview

• 

  Uterine body endometrium during the proliferative phase of the menstrual cycle

• 

  Uterine body endometrium during the secretory phase of the menstrual cycle overview

• 

  Uterine body endometrium during the secretory phase of the menstrual cycle

Abnormalities

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

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)
2. American Society for Reproductive Medicine (ASRM)

ESHRE-ESGE Classification

European Society for Gynaecological Endoscopy (ESHRE-ESGE)

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.
<pubmed>23894234</pubmed> See also ICD10 Congenital malformations of genital organs (Q50-Q56) Links: Genital System - Abnormalities | Uterus Development | image - simplified cartoon

Uterine Duplication

	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 - 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 Ectopic Page | Play

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
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.

Septate Uterus Ultrasound

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.

There has been recently a single report of a MRKH syndrome woman giving a live-birth after uterus transplantation from a deceased donor.

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? endocrine abnormalities | chemicals | drugs)

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

Cervical Cancer

ICD-11 2C77 Malignant neoplasms of cervix uteri - Primary or metastatic malignant neoplasm involving the cervix.
2C77.0 Squamous cell carcinoma of cervix uteri - A squamous cell carcinoma arising from the cervical epithelium. It usually evolves from a precancerous cervical lesion. Increased numbers of sexual partners and human papillomavirus (HPV) infection are risk factors for cervical squamous cell carcinoma. The following histologic patterns have been described: Conventional squamous cell carcinoma, papillary squamous cell carcinoma, transitional cell carcinoma, lymphoepithelioma-like carcinoma, verrucous carcinoma, condylomatous carcinoma and spindle cell carcinoma. Survival is most closely related to the stage of disease at the time of diagnosis. 2C77.1 Adenocarcinoma of cervix uteri - An adenocarcinoma arising from the cervical epithelium. It accounts for approximately 15% of invasive cervical carcinomas. Increased numbers of sexual partners and human papillomavirus (HPV) infection are risk factors. Grossly, advanced cervical adenocarcinoma may present as an exophytic mass, an ulcerated lesion, or diffuse cervical enlargement. Microscopically, the majority of cervical adenocarcinomas are of the endocervical (mucinous) type. 2C77.2 Adenosquamous carcinoma of cervix uteri 2C77.3 Neuroendocrine carcinoma of cervix uteri
Links: cervical cancer | human papillomavirus | viral infection | uterus

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". See the last report Cervical screening in Australia 2019Australian Institute of Health and Welfare 2019. Physical activity during pregnancy 2011–12. Cat. no. PHE 243. Canberra: AIHW. PDF</ref>, that used Pap tests as the screening tool (data for women screened between 1 January 2016 and 30 June 2017)

For more information see the external links below.

DOH Information Video
<html5media width="480" height="360">https://www.youtube.com/embed/a22VIXp3cxc</html5media> 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: mesometrium - surrounding the uterus mesosalpinx - surrounding the uterine tube mesovarium - surrounding the ovary Abnormalities include peritoneal endometriosis.

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

Reviews

Passos IMPE & Britto RL. (2020). Diagnosis and treatment of müllerian malformations. Taiwan J Obstet Gynecol , 59, 183-188. PMID: 32127135 DOI.

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

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  Human uterine tube ciliated epithelium SEM

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  Urogenital indifferent

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  Urogenital female

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  Mouse - paramesonephric duct

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  Ultrasound uterine and ovarian vascularity

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  Unicornate uterus

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  Historic drawing of the uterine tube (Reinier De Graaf)

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  Cervical mucus plug

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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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• Blue Histology Female Reproductive Tract

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Cite this page: Hill, M.A. (2023, December 5) Embryology Uterus Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Uterus_Development

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© Dr Mark Hill 2023, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G