Chapter 17- Sex Determination

1. Chapter 17- Sex Determination • Aristotle- Women are men with ______________ development • Pre-1900s- Sex considered to be determined by environment, age, nutrition • Early 1900s- Sex chromosome identified 1. Primary sex determination • Refers to “determination of ____________” • i.e. _______ vs. _________ • In Mammals- • Strictly determined by the __ chromosome • XY, XXY, XXXY, XXXXY are all ______ • There is no “default state”- gonad development is __________

2. 2. Secondary sex determination • Refers to “____________________” • i.e. penis and prostate vs vagina and uterus Also may affect body shape and size, voice…. • Dictated by ____________ produced by ______ If remove ______- female body is the “_________” Estrogen and testosterone play key roles • Estrogen instructs Mullerian Duct to become ___________________ • Testosterone instructs Wolfian Duct to become ____________, vas deferens • Testes also secrete ____ hormone to _________ Mullerian Duct

3. Gonad development Gonads derived from ___________ ____________________, next to kidneys nephros Recall Kidney development from Ch. 14 Nephric Duct Gonad Intermediate Migrating nephric duct cells induce surrounding mesenchyme to form nephros (tubules) Kidney, gonads Developing kidney The nephric duct is also called the_______________ Fig. 14.18

4. Gonad development Gonads __________ duct • Unlike other tissues, the gonad has two options- an ______or a ________ Kidney __________duct (nephric duct) Genital ridge Bipotential gonad SF1 WT1 LHX9

5. Gonad development • Genital ridge forms by ________ in human 4 weeks Genital ridge • Sex cords formed in gonad by _________ Sex cords 6 weeks • Now germ cells migrate into __________ At this stage, the gonad is still ________________

6. If male: • If male, _________ development continues, become ____________ that link to ___________________ Wolffian Duct • Mullerian duct ___________ Testis cords • Testis cords remain solid until __________ • At puberty, testis cords are _____________ to form ______________ and germ cells differentiate into _________ 8 weeks The wolffian duct becomes___ _______ to carry sperm to ________ 16 weeks

7. If female : • sex cords _____________ • ovaries to not connect to _______________ If female: • __________ sex cords are generated around germ cells Cortical sex cords • Cortical sex cords plus surrounding mesenchyme will eventually become the __________ that envelop the ___________ Wolffian Duct 8 weeks • The Mullerian duct becomes _______ uterus, cervix and _______________ Mullerian Duct • Wolffian duct _________ 16 weeks Follicles

8. Another view of sex determination Bipotential gonads Both Wolfian and Mullerian ducts are present prior to _____________ Mullerian duct Kidney Wolfian duct Either Wolfian and Mullerian duct must be degraded But, what dictates testes vs ovaries?? Male Female Fig. 17.4

9. Mechanisms of Primary sex determination in mammals SRY is the ______________________ gene. Extra DAX • SRY expression directs male _____________ • Located on the Y chromosome • encodes a ____ AA peptide • is a ___________________ • contains a HMG domain, common in many transcription factors • induces bends in DNA • SRY gene into XX mouse results in a ___________ mouse • Is ___________ but not ____________ to dictate testes • Other genes include _______ and ______ _______ may be the ovary-determining gene • DAX located on X chromosome • Two copies of DAX results in ___ female

10. If insert second DAX gene on X chromosome Two copies of ____ overrides the _____ gene: X X Y X X Y (Poorly formed gonad) Gonadal dysgenesis Testis Ovary • ______ is also critical for ovary formation Female Male Female

11. Model to explain primary sex determination in mammals Fig. 17.10 SRY competes with _____ to activate or repress the ____ gene. • If X + Y : ____ favored, SF1 expressed, _____ produced • SF1 may also inhibit ____ expression • If X (w/ 2____) + Y : SF1 repressed, ____ expressed, and ________ produced

12. Mechanisms of _________sex determination in mammals Testes secrete two _________ 1. ______- results in Mullerian duct degeneration Probably through apoptosis 2. _______________- results in Wolffian duct differentiation _____________ insensitivity syndrome- lack testosterone receptor, thus have testes but no uterus/oviducts; hence looks female Ovaries secrete __________ Estrogen is required for development of both _________ and _____________ ducts Fig. 17.11 Estrogen also promotes ___________ development

13. In contrast to humans, a. Drosophila sex is determined by the number of ___ chromosome ratio (where A is an autosome) X- male XX- female • The Y chromosome is active in _________ development b. Turtle and crocodile sex is determined by __________- % male c. The slipper snail sex is determined by ___________ Individuals are always _____, then can turn into _________ Temp Fig. 17.20

14. Sex determination in Drosophila • XX = females • XY = males Unlike mammals, the Y chromosome does not determine sex How is sex determined?? Answer: The X to autosome _____________ determines sex How is the X:A ratio interpreted?? Answer: Through activation of the _____________ gene • It is a ____________ between numerator proteins (on X) and denominator proteins (on A)

15. __________ (X) proteins __________Sxl transcription ___________ (A) proteins ________ Sxl gene transcription UGA PL PE Sxl gene 2 1 • In males, the _________ proteins win out • In females, the __________ proteins win out • The Sxl protein acts on: • Sxl gene “____” promoter (PL) to maintain • transcription • Sxl mRNA to splice out a _____________ 1 2 3 3 __________gene to splice out __________ 1 2 3 4 DNA RNA AAAAA

16. Female mRNA Pre- mRNA Male- mRNA Sex-lethal Stop codon Stop codon transformer Stop codon Stop codon doublesex Fig. 17.18 Sxl controls splicing of tra switch controls splicing of_________ (dsx) • Double sex in produced in both sexes, but ____________ protein is generated due to alternate splicing. Thus, the _____ protein type dictates _____ • A _____________ similar to dsx has been isolated