biological differentiation

Gender and sex not binary Language: Atypical reproductive structure labelling has varied, once pseudohermaphrodite or intersex "Accepted": disorders of sexual development

Embryological Reproductive Development Biological sex Not determined by any single bio factor Parts of the reproductive system forms in stages in utero Stages have own conditions Bipotentiality Undifferentiated structures that could develop into reproductive structures are available at each developmental stage Bio environment at time of structure development determines developmental direction Sometimes development results in structure formation that is not typical of either sex

==Stage 1 -- Chromosomal Sex== 46 chromosomes 44 autosomes 2 sex chromosomes Bipotentiality: Functional ovum typically has one X chromosome Sperm have either X or Y It determines chromosomal sex X larger (may not affect speed) Many sex-chromosome complements naturally occur (other than XX or XY) 1 in 450 have alternate makeup Common aneuploidies 45, X: Turner Syndrome (1 in 2500) Only single sex chromosome combo that is viable YO combo cannot survive X chromosome has more genes (1000, vs. 60 in Y) Cause is varied: may be sperm or ovum based Typically AFAB and raised as a girl, usually diagnosed before/at birth Typically no functional ovaries (infertile) No spontaneous secondary sex characteristics development (missing major estrogen source) Estrogen treatment 47, XXY: Klinefelter Syndrome (1 in 500-1000) Added sex chromosome can be carried by ovum, sperm, or both Slower testes growth, low sperm and androgen production

==Stage 2 -- Gonadal Sex== Gonads: glands that produce reproductive or germ cells Sex differentiation: ~6 weeks after conception Raw materials: cortex (outer rind) and medulla (inner rind) of undifferentiated gonads They are bipotential (develop into ovaries or testes) Primordial germ cells Form in yolk sac MUST migrate to undiff. gonads before differentiation into ovaries begin PGCs secondary role in testes dev. The earliest form of all the ova a female will ever have Development of male gonads: testes Needs: Presence of functional Y chromosome Complete and functional SRY gene (stimulates autosome to make HY antigen) HY antigen: Stimulates medulla of undiff. gonads to become testes Development of female gonads: ovaries Needs: Migration of PGCs to undiff. gonads Arrive at cortex, each surrounded by ball of cortical cells forming ovarian follicle Absence of functional Y chromosome (no SRY or HY antigen) Presence of at least 2 functional X chromosomes Gonad development Presence of any functional Y chromosome and HY antigen results in testes development With only 1 X chromosome (and no functional Y) gonads remain in undiff state -- gonadal streaks (Turner Syndrome) If XY, but SRY gene absent, gonads remain undiff -- gonadal streaks Swyer Syndrome Chromosomes -- 46, XY Y chromosome might lack functional or complete SRY gene Typically identified AFAB Very rare: 1 in 80,000 births No germ cells produced: infertile No spontaneous development of female secondary sex characteristics Usually gets hormone treatment

==Stage 3 -- Internal Genitalia== Internal reproductive plumbing Male: seminal vesicles, epididymis, ejaculatory ducts and tubes For complete development, embryo must HAVE source of and ability to respond to: Androgens Mullerian inhibiting factor Inductor substance All 3 typically produced by newly-formed testes Stimulate Wolffian ducts, regress Mullerian Female: uterus, oviducts (Fallopian), and (upper) vagina Mullerian ducts develop, regress Wolffian Must LACK these/ability to respond to: Androgens Mullerian inhibiting factor Inductor substance Raw materials: Wolffian and Mullerian ducts Both types found in all developing individuals Turner and Swyer syndrome: No testes = no androgen, MHF, inductor substance So typical female internal genitalia MRKH Syndrome Failure of Mullerian duct dev. In an XX individual Uterus doesn't develop Vagina shortened Cause unclear 1 in 4500 Identified usually when no menses at puberty

==Stage 4 -- External Genitalia== Undiff. raw materials Genital tubercle Labio-scrotal swelling Urogenital fold Ultrasound can detect development around 11 weeks post-conception About 100% accurate at 13 weeks Males Fetus must Have androgen source (usually testes) Have androgen receptors Then Genital tubercle -- penis Labio-scrotal swelling -- scrotum Urogenital fold -- urethra Females No androgens/androgen receptors Genital tubercle -- clitoris Labioscrotal swelling -- labia majora Urogenital fold -- labia minora Turner and Swyer syndrome No testes No androgen source Typical female external genitalia Androgen Insensitivity Syndrome Lacks androgen receptors XY chromosome complement Normal testes Ambig. internal genitalia Female external genitalia Almost all AIS individuals identify w/ female identity Congenital adrenal hyperplasia Excess androgen due to adrenal gland malfunction Effects vary May result in ambig. internal genitalia and male external genitalia in a XX individual w/ ovaries Identity often follows gender of rearing XY individuals need treatment (or early puberty is induced)