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Presentation on theme: "(and other animals) become male or female?"— Presentation transcript:

1 (and other animals) become male or female?
How do we (and other animals) become male or female?

2 Sexual Differentiation: Overview
Sex Determination The event that determines whether an individual will become male or female Sexual Differentiation The developmental process of becoming male or female

3 Sexual Differentiation: Overview
What is Sex? • Chromosomal sex • Gonadal sex • Gametic sex • Hormonal sex • Morphological sex • Behavioral sex • Gender identity • Gender role • Legal sex

4 Sexual Differentiation: Overview
Jost’s Model of Sexual Differentiation:

5 What determines gonadal sex (development of testes vs. ovaries)?

6 Gonadal Differentiation
Nelson 2005 Fig. 3.4 Germinal ridge: • Thickened ridge of tissue on surface of each mesonephros (protokidney) • Can develop into a testis or an ovary

7 Gonadal Differentiation: SRY Gene
(Sex-Determining Region of Y Chromosome) TDF binds to DNA and regulates genes controlling development of testes

8 Gonadal Differentiation: SRY Gene
Evidence for role of SRY gene: • SRY is activated shortly before gonads differentiate. • XY phenotypic females often have mutations in SRY (humans, mice). • XX phenotypic males often have SRY-containing translocation to X chromosome.

9 Gonadal Differentiation: SRY Gene
Evidence for role of SRY gene: • SRY is activated shortly before gonads differentiate. • XY phenotypic females often have mutations in SRY (humans, mice). • XX phenotypic males often have SRY-containing translocation to X chromosome. • XX transgenic mice: introduction of SRY causes testicular development. BUT: Autosomal genes also contribute to testis development.

10 Gonadal Differentiation: Ovary-Determining Genes
• Unclear if any exist. • Have been hypothesized to exist and to be switched off in males by activation of SRY gene. • Two X chromosomes necessary for normal ovarian development.

11 Gonadal Differentiation
• Germinal ridge is initially indifferent/bipotential. • TDF expression  no TDF expression  • TDF acts locally – not blood-borne. • In mammals, sex steroids have limited effects. Human fetal ovaries Human fetal testes

12 of the internal reproductive tracts?
What determines differentiation of the internal reproductive tracts?

13 Reproductive Tract Differentiation
2 duct systems initially present in each embryo: Wolffian ducts Müllerian ducts Nelson 2005 Fig. 3.5

14 Reproductive Tract Differentiation
1. Wolffian ducts • T  • No T  2. Müllerian ducts • Müllerian inhibitory hormone (MIH) from testes  • No MIH 

15 Reproductive Tract Differentiation
Silverthorn Fig. 26-3

16 Reproductive Tract Differentiation
Testes No Testes T MIH No T No MIH Wolffian ducts Müllerian ducts vas deferens epididymis seminal vesicles regression regression fallopian tubes uterus cervix

17 of the external genitalia?
What determines differentiation of the external genitalia?

18 Differentiation of External Genitalia
Nelson Fig. 3.7

19 Differentiation of External Genitalia
• Bipotential anlagen Genital folds, genital tubercle Identical in males and females until week 6-8 • Effects of androgens (males) Genital tubercle  penis Genital folds  scrotum (testes descend later) • Absence of androgens (females) Genital tubercle  clitoris Genital folds  labia

20 Summary of Sexual Differentiation
Silverthorn Table 26-1

21 ANOMALIES OF SEXUAL DIFFERENTIATION
What can go wrong, and what do the exceptions tell us about the rules?

22 True Hermaphroditism • Both ovarian and testicular tissue are present in the same individual – ovary on one side, testis on the other – “ovotestes” • Uncommon • Usually 46,XX; sometimes 46,XX/46,XY chimerism or mosaicism • Phenotypically variable • Some are fertile as females

23 Anomalies in Chromosomal Females: Turner Syndrome (XO)
• Gonadotropin levels: high in infancy and post-pubertally; normal prepubertal hiatus Immature genital tract & external genitals; short stature • Often lethal prenatally

24 Anomalies in Chromosomal Females: Turner Syndrome (XO)
Wilson & Foster 1987 Fig

25 Anomalies in Chromosomal Females: Congenital Adrenal Hyperplasia (CAH)
• Causes masculinization of the external genitalia in females. • Can be mild to severe. • Can be treated with surgery and exogenous steroids.

26 Anomalies in Chromosomal Females: Congenital Adrenal Hyperplasia (CAH)
Adrenal Cortex Zona glomerulosa Zona fasciculata Zona reticularis X X High androgens Low aldosterone Low cortisol

27 Anomalies in Chromosomal Females: Congenital Adrenal Hyperplasia (CAH)
Money 1987

28 Anomalies in Chromosomal Females: Congenital Adrenal Hyperplasia (CAH)
Wilson & Foster 1987 Fig

29 Anomalies in Chromosomal Males: Androgen Insensitivity Syndrome (AIS)
(Testicular Feminization (TFM)) • Testes develop; Wolffian and Müllerian ducts regress; external genitalia appear female. • Female body type and gender identity, but sterile.

30 Anomalies in Chromosomal Males: 5a-Reductase Deficiency
(Guevodoces, Penis at Twelve) • No 5a-reductase – can’t convert T to DHT. • XY infants have ambiguous genitalia and small, undescended testes. 5a-Reductase 5a-Dihydro-testosterone (DHT) H 5 17-beta Estradiol (E2) Aromatase 17 A Testosterone (T) 19

31 Anomalies in Chromosomal Males: 5a-Reductase Deficiency
(Guevodoces, Penis at Twelve)

32 Anomalies in Chromosomal Males: 5a-Reductase Deficiency
(Guevodoces, Penis at Twelve)

33 Anomalies in Chromosomal Males:
Trisomies 1. XXY (Klinefelter Syndrome) Phenotypically male Small testes, androgen deficiency, low sperm production (sterile) Gynecomastia Low intelligence Nelson 2005 Fig 3.14 XXY XYY 2. XYY Phenotypically male Normal sexual development Extremely tall Low intelligence, Hyperactive Antisocial


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