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Sexual Development & Differentiation

Sexual Development & Differentiation. Sex & Gender. Sex and Gender. Sex genetic sex - chromosomes anatomical sex - internal and external genitalia sexual identity - one’s identity as male or female. Sex and Gender. Gender social meaning attached to being male or female

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Sexual Development & Differentiation

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  1. Sexual Development & Differentiation

  2. Sex & Gender

  3. Sex and Gender • Sex • genetic sex - chromosomes • anatomical sex - internal and external genitalia • sexual identity - one’s identity as male or female

  4. Sex and Gender • Gender • social meaning attached to being male or female • gender identity - sense of being male or female • gender role - expectations about how a male or female should behave

  5. SCIENTIFIC BASIS OF FERTILITY OVARIAN DIFFERENTIATION SEX DIFFERENTIATION TESTIS SPERMATOGENESIS AND SPERM TRANSPORT FOLLICULAR GROWTH AND OVULATION SPERM - OOCYTE FUSION

  6. Gender identity is the end result of genetic hormonal and morphologic sex as influenced by the environment Genetic sex (chromosome ) ¯ Gonadal sexual (testis, ovaries) ¯ Hormones affecting sex development of fetus + Hormone production at Puberty External genitalia CNS Sex assignment and rearing Gender identity

  7. Normal Prenatal Development:Genetics • Chromosomes • each human cell contains 46 chromosomes, occurring in pairs • 23 pairs of chromosomes • 22 autosomes (determines e.g., hair color) • 23rd pair are the sex chromosomes • male: XY • female: XX

  8. Normal Prenatal Development: Genetics….

  9. Normal Prenatal Development: Genetics…. • Germ cells: • male: sperm - contains “X” or “Y” • female: ovum - contains an “X” • “Y” chromosome contains less genetic material than “X” chromosome

  10. Normal Prenatal Development: Genetics…. MotherFather XX XY X X X Y XX XY XX XY female malefemale male

  11. Normal genital development • The mammalian fetus has an inherent tendency to develop into a female. • The primitive human gonad starts to develop between the 4th and 6th week of fetal life deriving from cells of endodermal origin that migrate from the yolk sac to the genital ridge. • The gonad is initially bipotential and develops into a testis or ovary depending upon karyotype.

  12. Normal Sex Differentiation Intermediate Mesoderm WT/SF1 XX/XO XY/XXY Bipotential gonads SRY SOX9 Wnt4 DAX1- Antitestis Testis Ovary Leydig cell Granulosa Cell Theca Cell Sertoli cell No AMH No T 5-R AMH T DHT Mullerian Duct Follicles No mullerian Duct Wolffian Duct Oestrogen Progesterone Male internal genitalia Male External Genitalia Female Internal Genitalia Rs No uterus

  13. Male genital development

  14. 6th weeks gestations, still in bipotensial gonad. Fetus has genital duct premordial (Mullerian duct and Wolfian duct) and axternal genitalia premordial . 8th-12th gestation, placental gonadotropin increase: stimulate Leydig cell for testoteron producing and sertoli cell for Mullerian inhibiting factor (MIF) producing .

  15. Normal Prenatal Development:Internal & External Genitalia • Sexual differentiation: Gonadal development • 8 weeks gestation • Y chromosome synthesis of H-Y antigen • Male: H-Y antigen causes undifferentiated sex glands to develop into testes • Female: lack of H-Y antigen causes undifferentiated sex glands to develop into ovaries

  16. Normal Prenatal Development:Internal & External Genitalia • Sexual differentiation: Duct development • both sexes start out with two systems: • Mullerian ducts - will develop into fallopian tubes, uterus, inner vagina • Wolffian ducts - will develop into epididymis, vas deferens, and seminal vesicles

  17. Male sexual differentiation is initiated by the SRY gene on the short arm of the Y chromosome. • Under the influence of SRY, the undifferentiated gonad forms a testis: testosterone stimulates the wolffian structures (epididymis, vas deferens, and seminal vesicles), and anti-Mullerian hormone suppresses the development of the Mullerian structures (fallopian tubes, uterus, and upper vagina).

  18. Male genital development • Presence of Y chromosome • Testicular hormone production • Normal responsiveness of androgen-dependent tissues

  19. The conversion of testosterone to dihydrotestosterone occurs in the skin of the external genitalia and masculinizes the external genital structures. • Most of this male differentiation takes place by about 12 weeks, after which the penis grows and the testes descend into the scrotum.

  20. CAH 46 XX

  21. Infants whose genitalia are obviously ambiguous are investigated at birth so that sex of rearing can be assigned. • In many cases, however, appearances are deceptive: • An infant with what appears to be bilateral cryptorchidism might be assumed to be a boy because of a normal-appearing phallic structure but in fact may be a girl with severe virilizing congenital adrenal hyperplasia (CAH).

  22. An apparent female infant with only slight clitoral hypertrophy may be a genetic male with severe androgen insensitivity, necessitating eventual removal of the testicles to avoid malignant degeneration. • It is necessary, therefore, to have well-defined clinical criteria for the investigation of intersexuality

  23. Female genital development • Spontaneous process independent of hormonal influences. • Without Y chromosome the primitive gonads develop into ovaries. • Mullerian ducts develop into female internal genitalia • Lower end of vagina forms from the urogenital sinus • External genitalia similarly develop spontaneously.

  24. Normal Prenatal Development:Internal & External Genitalia • Undifferentiated stage: • 0-7 weeks gestation • male and female external genitals the same • urogenital fold • genital groove • genital tubercle • labioscrotal swelling • male and female internal genitalia the same - undifferentiated sex glands

  25. Normal Prenatal Development:External Genitalia

  26. External Genitalia

  27. Normal Prenatal Development:Internal Genitalia

  28. Male (XY) • Testes secrete testosterone and Mullerian-inhibiting hormone • testosterone - Wolffian ducts begin to develop • Mullerian-inhibiting hormone - inhibits further development of Mullerian ducts - they shrink and degenerate • Female (XX) • absense of Mullerian-inhibiting hormone - Mullerian ducts develop • absense of testosterone - Wolffian ducts degenerate

  29. Normal Prenatal Development:Internal & External Genitalia • Sexual differentiation: Genital development • Male (XY): testosterone causes unisex genitalia to develop into penis and scrotum • testosterone converted to dihydrotestosterone • dihydrotestosterone causes the external appearance of scrotum and penis • Female (XX): absence of testosterone causes unisex genitalia to develop into clitoris, labia, vaginal opening, etc. NOTE: The default is the develop as a female. Male hormones are needed to promote differentiation into a male

  30. Normal Prenatal Development: The Brain • Sexual differentiation: • Male: • Testosterone secreted → blood → brain • testosterone converted to estradiol and DHT in the brain • estradiol masculinizes the brain • Female: • alpha-fetoprotein binds to estradiol • prevents estradiol from entering the brain • protects female brains from being masculinized by estradiol

  31. Hypospadias

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