Alfred Jost - French embryologist, research in the 1940s and 1950s. He found that regardless of genetic sex, these rabbits developed as females. Conclusion: male development involves a gene/genes that trigger the development of testes, which in turn release hormones that masculinize the rest of the body.
Person on the left; Turner’s syndrome. Single X=X0, or single X and smaller portion of second X. Both Xs are necessary to develop normal ovaries. Thus, tend to lack ovarian hormones. Short in stature, do not enter puberty, infertile. Small breasts. Treatment: growth hormone + androgens to increase growth; estrogens for secondary sex characteristics; estrogen + progesterone for menstrual cycle.
David Page, infertility clinic. People go to infertility clinic, because could not get pregnant. Physical exam and genotyping of sex chromosomes Normal looking males, but with XX genotype, piece of Y-chromosome translocated to X SRY = Sex-determining Region of the Y-chromosome Normal looking females, with XY genotype, yet missing crucial gene.
What does the SRY gene do? SRY gene turned on. Protein that is a transcription factor, regulates expression of other genes; SRY make sertoli cells instead of granulosa cells; absence of SRY, granulosa cells form. DAX-1 gene located on X-chromosome; expressed about same time as SRY. Normally SRY overrules DAX-1, however 2 copies of DAX-1 on the same X cause XY embryo to develop into female
Intersex = biological sex is ambiguous or intermediate between male & female Gonadal intersexuality is extremely rare. Possess both ovarian and testicular tissue within gonad Most are XX; SRY translocated to X and only partially expressed or chromosomal chimera with some cells having XY genotype and others XX.
Gametes to not originate from genital ridges under influence of SRY & DAX-1 Yolk sac - temporary non-embryonic tissue - source of primoridal germ cells Germ cell that will grow/germinate to form ova and sperm. Travel from yolk sac and find a home within genital ridge developing into ovary or testis; attracted by some chemical signal Granulosa cells trigger development of thecal cells; sertoli cells trigger development of Leydig cells
X-chromosome large, therefore many genes; cause big sex difference, dosage problem, too much expression of those genes on X bad In females, one of two X-chromosome permanently inactivated very early in development. Random if it is paternal or maternal X Progeny of parent cells have same X inactivated. Barr body: present in females, but absent in males, inactivate X condensed structure visible from cell sample as dark spot in nucleus.
About 6-wk postconception. Gonads beginning to form as either testes or ovaries, two ducts from gonads to exterior of body: Wolffian, Mullerian; precursor to internal parts of male and female sexual anatomy Female is default pathway, no hormonal signal needed. Males need signal to override female plan. Male gonad secretes two hormones: Anti-Mullerian homone causing regression of Mullerian ducts; androgens (testosterone) promoting development of Wolffian ducts
Common precursors like gonads, but unlike internal genitalia. Again, female plan is the default position, need overriding signal in male Circulating Testosterone, 5 alpha reductase
XY-males; produce AMH & T so gonads & internal genitalia develop normally. External genitalia do not fully develop in male direction; labia-like structures instead of scrotum, phallus resembling a clitoris instead of a penis Puberty: increase in testosterone; further development in male appearance. Dominican Republic
Larger in males than females
Motor neurons that support ejaculation in males.
Systems & BehavioralSystems & Behavioral
Rob ContrerasRob Contreras
Professor of Psychology andProfessor of Psychology and
Director, Program in NeuroscienceDirector, Program in Neuroscience
Sexual DevelopmentSexual Development
Sexual dimorphismSexual dimorphism
internal genitaliainternal genitalia
external genitaliaexternal genitalia
Female development - “default” pathwayFemale development - “default” pathway
Typical and atypical pathwaysTypical and atypical pathways
Alfred Jost's experiments on rabbitsAlfred Jost's experiments on rabbits
Chromosomal AnomaliesChromosomal Anomalies
• Turner’s syndrome Klinefelter’s syndromeTurner’s syndrome Klinefelter’s syndrome
SRY = male
Internal sex OK
Genetic basis of sex determinationGenetic basis of sex determination
Molecular genetics of gonad developmentMolecular genetics of gonad development