Testis Development

From Embryology
Historic testis drawing

Introduction

The male gonad is the testis. The initial difference in male and female gonad development are dependent on testis-determining factor (TDF) the protein product of the Y chromosome SRY gene. Recent studies have indicated that additional factors may also be required for full differentiation. Within the developing testis the three main differentiating cell types are: gamete forming cells (spermatogonia), support cells (Sertoli cells) and hormone secreting cells (Leydig or interstitial cells).

The seminiferous tubules are considered the parenchyma of the testis.

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

| Y Chromosome | Puberty | original page

Some Recent Findings

  • Oestrogen blocks the nuclear entry of SOX9 in the developing gonad of a marsupial mammal.[1] "We have uncovered a mechanism by which oestrogen can regulate gonadal development through the nucleocytoplasmic shuttling of SOX9. This may represent an underlying ancestral mechanism by which oestrogen promotes ovarian development in the gonads of nonmammalian vertebrates. Furthermore, oestrogen may retain this function in adult female mammals to maintain granulosa cell fate in the differentiated ovary by suppressing nuclear translocation of the SOX9 protein."
  • FGF signaling directs a center-to-pole expansion of tubulogenesis in mouse testis differentiation.[2] "These observations imply that center-to-pole FGF9 diffusion directs a poleward expansion of testiculogenic programs along the anteroposterior axis of developing XY gonads."

Development Overview

Male urogenital development (stage 22)

Sex Determination

  • Humans (week 5-6)
  • Germ cells migrate into gonadal ridge
  • Gonads (male/female) identical at this stage, Indifferent

Gonad Development

  • dependent on sex chromosome
  • Y testes
  • No Y ovary

SRY

SRY protein (Testes determining factor, TDF) binds DNA Transcription factor, Bends DNA 70-80 degrees

Internal Genital Organs

  • All embryos form paired
  • Mesonephric duct, see kidney development
  • Paramesonephric duct, Humans 7th week Invagination of coelomic epithelium Cord grows and terminates on urogenital sinus
  • Male Gonad (testes) secretes Mullerian duct inhibitory factor (MDIF) which causes regression of paramesonephric duct
  • Male Gonad (testes) secretes Testosterone which retains mesonephric duct

External Genital Organs

  • All embryos initially same (indifferent)
  • Testosterone differentiates male

Sertoli Cells

Adult Seminiferous tubule showing spermatozoa developmental stages
Gonadal supporting cell development

These are the support cells located within the seminiferous tubule. Their differentiation is regulated by the presence of a Y chromosome and in turn regulates Leydig cell differentiation. At puberty the immature Sertoli cells cease to proliferate and differentiate.

Molecular factors: Follicle Stimulating Hormone (FSH) -> Krüppel-like factor 4 (KLF4)

Krüppel-like factor 4 (KLF4) - zinc finger transcription factor, terminal differentiation of epithelial cells.

Epidermal Growth Factor (EGF)

Transforming Growth Factor-beta (TGFbeta)

Leydig Cells

Seminiferous tubule cross-section and supporting cells

Interstitial or Leydig cells, named after german zoologist Franz von Leydig (1821 - 1908).

These cells produce the male testicular androgens and have a role during life prenatally (fetal) and postnatally during puberty onward.

Fetal Leydig Cells

Have a hormonal role in male genitalia differentiation and are lost postnatally. These cells arise approximately at 6 weeks (human) and 12.5 dpc (mouse) and there appears to be differences in hormonal sensitivity between the species. Their initial differentiation requires both luteinizing hormone (LH) and adrenocorticotrophic hormone (ACTH) and therefore normal pituitary development.

(More? Endocrine - Pituitary Development)

Adult Leydig Cells

Have a hormonal role in puberty, secondary sex characteristics and sexual maturation. Their initial differentiation from peritubular mesenchymal cells does not require gonadotropin, but development and function are dependent upon luteinizing hormone (LH).

The cells differentiate with three discrete stages (newly formed, immature, mature) leading to a decrease in proliferation and increasing testosterone biosynthetic capacity. Insulin-like growth factor I (IGF-I) stimulates proliferation of immature cells and promotes their maturation. Testosterone and estrogen inhibit the process of precursor cell differentiation and may be responsible for the cessation of proliferation in the adult Leydig cells.

Testis Descent

Testis-descent start.jpg Testis-descent end.jpg Testis 001 icon.jpg
Before Descent End of Descent Testis Descent Movie

Cryptorchidism

Cryptorchidism
Newborn - cryptorchidism normal birthweight[3]
  • abnormality of either unilateral or bilateral testicular descent, occurring in up to 30% premature and 3-4% term males.
  • Descent may complete postnatally in the first year, failure to descend can result in sterility.

Testis descent is thought to have 2 phases:

  1. transabdominal descent - dependent on insulin-like hormone 3 (INSL3).
  2. inguinoscrotal descent - dependent on androgens.

Management of cryptorchidism in children: guidelines.[4] "Cryptorchidism is best diagnosed clinically, and treated by surgical orchiopexy at age 6-12 months, without a routine biopsy. If no testis is palpable, or if other signs of hypovirilisation such as hypospadias are present, the chromosomal sex and hormonal status must be assessed. Laparoscopy is the best way of diagnosing and managing intra-abdominal testes."

Puberty

In humans at puberty, hormonal and morphological changes occur within the gonad and other systems (secondary sex characteristics). Within the testis the immature Sertoli cells cease to proliferate and differentiate. Spermatogonium proliferate and spermatogenesis begins, and it takes about 70 days for cells to mature from the diploid spermatogonium to a primary spermatocyte. This maturation occurs in waves along the seminiferous tubules.

Links: Puberty Development

Molecular

Sry

Links: Sry

Sox9

  • autosomal transcription factor
  • Development of XY females - presence of only a single functional copy of the transcription factor encoding genes SOX9, SF1, or WT1 (Note- not all XY humans are sex-reversed if only a single copy of a normal SF1 or WT1 allele is present)
  • A nuclear export signal within the high mobility group domain regulates the nucleocytoplasmic translocation of SOX9 during sexual determination[5]


Other roles

  • Cartilage - essential for chondrocyte differentiation
  • Hearing - otic placode formation, maintenance of progenitors in the otic epithelium


Links: Sox9 | Cartilage Development | Inner Ear Development

Fog2

  • transcription factor
  • dosage critical for fetal testis development in mice[6]

Gata4

  • transcription factor
  • dosage critical for fetal testis development in mice[6]

References

  1. <pubmed>20040496</pubmed>| PMC2940779 | BMC Biol.
  2. <pubmed>20040496</pubmed>
  3. <pubmed>18032558</pubmed>| Hum Reprod Update.
  4. <pubmed>18726735</pubmed>
  5. <pubmed>12169669</pubmed>| PMC123233 | PNAS
  6. 6.0 6.1 <pubmed>17848526</pubmed>PMC1986601 | PNAS


Reviews

Articles

<pubmed>20664245</pubmed> <pubmed>20610195</pubmed>

Search PubMed

Search Pubmed: Testis Development | Sry | Sox9

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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

| Y Chromosome | Week 1 - Spermatogenesis | Ovary | Puberty | original page


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

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G