BGDB Sexual Differentiation - Fetal

From Embryology
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Practical 12: Sex Determination | Early Embryo | Late Embryo | Fetal | Postnatal | Abnormalities | Quiz | Audio | 2013 Notes PDF

Introduction

In the previous section we observed late embryonic male genital development and now in fetal development we will observe early fetal female development. Then we will explore fetal development of the external genitalia and gonadal descent.

Week 10 Female

Human week 10 fetus 01.jpg
Human week 10 fetus 03.jpg
Human- fetal week 10 planes icon.jpg
  • week 10 to 12 - female in absence of Sry expression, within the gonad cortical cords extend from the gonad surface epithelium. Primordial germ cells which have entered the gonad form oogonia primordia, surrounding mesenchyme forms the follicular primordia.
  • The selected images below show the general anatomy of the pelvic region of the an early female fetus (10 week, 40mm).
  • This first image shows the relative positions of the kidney (plane A most lateral) and developing ovary (plane A and B away from the midline) and internal genitalia (plane C and D in the midline).
  • The selected images below show sections through the pelvic region showing anatomical relationships between the developing female gonad (ovary), internal genital tract and external genitalia.
  • Note the relative immaturity of the external genitalia, which at this time would appear identical to the male.
Fetal 10wk urogenital 1.jpg Fetal 10wk urogenital 2.jpg
Plane A (most lateral) Plane B (lateral)
Fetal 10wk urogenital 3.jpg Fetal 10wk urogenital 4.jpg
Plane C (medial) Plane D (midline)

Uterus and Vagina

Paramesonephric duct.jpg

Mouse paramesonephric duct (Müllerian duct)[1]

This mouse image shows the relationship between the mesonephric and paramesonephric ducts opening into the urogenital sinus.
  • The paramesonephric duct began as an infold of surface epithelium lying along the surface of the genital ridge.
  • Estrogens, both maternal and fetal, stimulate its development and that eventually of the external female fetal genital structures.
  • In contrast, the mesonephric duct regresses, remnants of this duct may remain lying within the broad ligament.
Female Uterus and Vagina (between week 9 and 20)
Note - the entire vagina is formed from the paramesonephric (Müllerian) duct and does not have a contribution from the urogenital endoderm.


  • The initially paired ducts fuse in the midline forming the single body of the uterus.
  • The ducts remain separate laterally where they form the uterine tubes (Fallopian tubes, uterine horns).
  • The ducts peripheral attachment site to the urogenital sinus wall (yellow) is is described as the Müllerian tubercle.
  • The fused ducts also generate the vagina, under the influence of BMP4.
  • Estrogen will also later alter the vaginal epithelium.

The uterus and broad ligament will eventulaly divide the pelvic cavity into two separate pouches.

  • posteriorly - uterorectal pouch (pouch of Douglas)
  • anteriorly - uterovesical pouch

Genital Movie Links

Female: Ovary Development Movie - MP4 movie | External Genital Movie - MP4 movie | Internal Genital Movie - MP4 movie | Ovary Development | Uterus Development | Vagina Development | Movies
Male: Testis Development Movie - MP4 movie | External Genital Movie - MP4 movie | Testis Descent Movie - MP4 movie | Penis Development | Testis Development | Movies
Fetal uterus growth.jpg This graph shows the growth during the fetal period of the uterus between week 19 and 38.[2]
  • During this time the uterine circumference increases from 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.

External Genitalia

This next section will look at the development of the external genitalia using a series of animations and online resources.

Female External Genitalia

External Genital Female Development Movie

Animation showing the development of external female genitalia from the indifferent external structure (week 9 to 12 approximately).
  • original cloacal membrane becomes separated into the urogenital membrane and anal membrane
  • urogenital folds beneath the genital tubercle remain separate (unfused)
    • forming the inner labia minora
  • second outer skin folds form the larger labia majora
    • either side of the developing vestibule of the vagina
  • genital tubercle (top of the animation) forms the glans of the clitoris

Male External Genitalia

Testosterone metabolism

External Genital Male Development Movie

Animation showing the development of external male genitalia from the indifferent external structure (week 9 to 12 approximately).

The reduction of Testosterone to active metabolite, 5α-dihydrotestosterone (DHT) is carried out by the enzyme 5α-reductase expressed in the region or male external genitaila and prostate gland. Note that there are several 5α-reductase isoforms that differ in both tissue distribution and kinetics.

  • original cloacal membrane becomes separated into the urogenital membrane and anal membrane (identical to female).
  • urogenital folds beneath the genital tubercle begin to fuse in the midline
  • skin folds either side for the scrotum
    • which also has a midline fusion, the raphe
  • scrotal sac is initially empty and is an attachment site for the gubernaculum
  • descent of the testes begins generally during week 26 and may take several days.

External Genitalia Comparison

Keith1902 fig098.jpg

Gonad Descent

Gonad Blood Supply Development

Animation shows the descent of the gonads and their blood supply.
  • both male and female gonads undergo this relative descent within the peritoneal cavity
    • this descent carries the gonads away from the kidneys which are ascending
  • during the fetal period, male testes will continue to descend out of the peritoneal cavity

Internal Gonad Descent

Testes Descent

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The animation shows the descent of the testes (between week 7 to 38, birth).

Descent of the testes into the scrotal sac begins generally during week 26 and may take several days.

  • testis (white) lies in the subserous fascia (spotted)
  • a cavity processus vaginalis evaginates into the scrotum
  • gubernaculum (green) attached to the testis shortens drawing it into the scotal sac
  • as it descends it passes through the inguinal canal extends
  • from the deep ring (transversalis fascia)
  • to the superficial ring (external oblique muscle)

Incomplete or failed descent can occur unilaterally or bilaterally, is more common in premature births, and can be completed postnatally. (see also cryptorchidism).


Testis Descent Movie

Testis-descent start.jpgTestis-descent end.jpg Data from a study of male human fetal (between 10 and 35 weeks) gonad position[3]
  • 10 to 23 weeks - 10 % had migrated from the abdomen and were situated in the inguinal canal
  • 24 to 26 weeks - 58 % had migrated from the abdomen
  • 27 to 29 weeks - 17 % had not descended to the scrotum

Fetal Kidney

Nephrogenesis is the formation of the functional nephron occurs in the fetal period with all of the nephrons formed by 30 to 34 weeks (GA 32 to 36 weeks). There are no new nephrons formed after this period.
  • ureteric bud - (UB) collecting duct
  • metanephric mesenchyme - (metanephric blastema) remainder of the nephron

Renal development cartoon01.jpg

Nephron histology.jpg

Adult Nephron Structure

Additional Information

Additional Information - Content shown under this heading is not part of the material covered in this class. It is provided for those students who would like to know about some concepts or current research in topics related to the current class page.

Testes Descent Timeline

Data from a study of male human fetal (between 10 and 35 weeks) gonad position.[3]

  • 10 to 23 weeks - (9.45%) had migrated from the abdomen and were situated in the inguinal canal
  • 24 to 26 weeks - (57.9%) had migrated from the abdomen
  • 27 to 29 weeks - (16.7%) had not descended to the scrotum

A second study looked at the position of the testes[4]

  • 33 weeks fetal testes had descended to the scrotum
  • between 33 to 40 weeks (term) both testes have normally descended to the scrotum

Failure of descent (cryptorchidism) either unilateral or bilateral testicular descent, occurring in up to 30% premature and 3-4% term males.

Cryptorchidism in common eutherian mammals.[5]- Species comparison of descent timeline

Prostate

Under the influence the gonad-derived fetal testosterone acting through androgen receptors, a region of the urogenital sinus mesenchyme differentiates to form the primordial prostate buds. The buds then signal back to the overlying epithelium, inducing duct formation.

Prostate Development

Renal Stages

Nephron development 01.jpg

Nephron development <ref name=PMID23338209> Paola Romagnani, Laura Lasagni, Giuseppe Remuzzi Renal progenitors: an evolutionary conserved strategy for kidney regeneration. Nat Rev Nephrol: 2013, 9(3);137-46 PubMed 23338209

<ref>

The morphological events and localization of renal progenitors occurring during nephron development in the adult human kidney.

Mesenchymal cells near the tips of the branching ureteric bud undergo epithelial transition and differentiate through a series of forms made up of renal progenitors (red)

  • a - condensed aggregate forms
  • b - renal vesicle forms
  • c - S-shaped body (red), renal progenitors are localised, at this stage podocyte-committed progenitors (red + blue) as well as tubular-committed progenitors (orange) can already be seen.
  • d - mature nephron, renal progenitors (red), podocyte-committed progenitors (red + blue), as well as tubular-committed progenitors (orange) are distributed along the nephron.
  • e - glomerulus, renal progenitors (red) are localized at the urinary pole of the Bowman capsule. Podocyte-committed progenitors (red + blue) localize along the Bowman capsule.

Glomerulus Structure

Nephron histology 01.jpg Nephron histology 02.jpg

Hyperfiltration Hypothesis

Developmental renal mass reduction could result in glomerular alterations that may have adverse effects in long-term renal health. There are also no easy methods to easily detect a reduced nephron reserve.

B M Brenner, E V Lawler, H S Mackenzie The hyperfiltration theory: a paradigm shift in nephrology. Kidney Int.: 1996, 49(6);1774-7 PubMed 8743495

Michiel F Schreuder Safety in glomerular numbers. Pediatr. Nephrol.: 2012, 27(10);1881-7 PubMed 22532329

Historic Genital

Historic Disclaimer - information about historic embryology pages 
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Pages where the terms "Historic Textbook" and "Historic Embryology" appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms and interpretations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

Spaulding MH. The development of the external genitalia in the human embryo. (1921) Contrib. Embryol., Carnegie Inst. Wash. Publ. 81, 13: 69 – 88.

Fleming AM. The internal genital organs of a female foetus of 15 cm length. (1927) J Anat. 61: 232–246. PMID 17104136

Keith (1902)
Keith A. Human Embryology and Morphology. (1902) London: Edward Arnold.

Chapter 9 - The Uro-genital System

Gary's Anatomy (1918)
Gray H. Anatomy of the human body. (1918) Philadelphia: Lea & Febiger.
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Practical 12: Sex Determination | Early Embryo | Late Embryo | Fetal | Postnatal | Abnormalities | Quiz | Audio | 2013 Notes PDF

References

  1. Ulrich Drews, Osman Sulak, Philipp A Schenck Androgens and the development of the vagina. Biol. Reprod.: 2002, 67(4);1353-9 PubMed 12297555
  2. D Soriano, S Lipitz, D S Seidman, R Maymon, S Mashiach, R Achiron Development of the fetal uterus between 19 and 38 weeks of gestation: in-utero ultrasonographic measurements. Hum. Reprod.: 1999, 14(1);215-8 PubMed 10374123
  3. 3.0 3.1 F J Sampaio, L A Favorito Analysis of testicular migration during the fetal period in humans. J. Urol.: 1998, 159(2);540-2 PubMed 9649288
  4. M A Malas, O Sulak, A Oztürk The growth of the testes during the fetal period. BJU Int.: 1999, 84(6);689-92 PubMed 10510117
  5. R P Amann, D N R Veeramachaneni Cryptorchidism in common eutherian mammals. Reproduction: 2007, 133(3);541-61 PubMed 17379650




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Cite this page: Hill, M.A. 2017 Embryology BGDB Sexual Differentiation - Fetal. Retrieved September 24, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/BGDB_Sexual_Differentiation_-_Fetal

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© Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G