11. Gonadal Sex Differentiation | SRY→SOX9 Pathway, Ovarian Signals (WNT4/FOXL2) | USMLE Step 1 скачать в хорошем качестве

11. Gonadal Sex Differentiation | SRY→SOX9 Pathway, Ovarian Signals (WNT4/FOXL2) | USMLE Step 1

𝐒𝐮𝐛𝐬𝐜𝐫𝐢𝐛𝐞 𝗙𝐨𝐫 𝗠𝐨𝐫𝐞 𝗜𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧 𝐨𝐧 𝗛𝐞𝐚𝐥𝐭𝐡 👩‍⚕‍ 𝐚𝐧𝐝 𝗠𝐞𝐝𝐢𝐜𝐢𝐧𝐞💉🩺💊 𝐘𝐨𝐮𝐭𝐮𝐛𝐞 :    / @draishwaryakelkar   📌𝗙𝗮𝗰𝗲𝗯𝗼𝗼𝗸 :   / draishwaryakelkar   📌𝗧𝘄𝗶𝘁𝘁𝗲𝗿:   / aishwayadr   📌𝗜𝗻𝘀𝘁𝗮𝗴𝗿𝗮𝗺 :   / clinical.learning   🧬 Gonadal Sex Differentiation | USMLE Step 1 | SRY→SOX9 Pathway, Ovarian Signals (WNT4/FOXL2) & Classic DSD Vignettes YouTube Description: Master the logic of gonadal sex differentiation from the indifferent embryo to testis or ovary—exactly how USMLE Step 1 tests it and how Western clinicians reason through DSD (differences/disorders of sex development). Begin with the bipotential gonad (weeks 4–6) arising from intermediate mesoderm and colonized by primordial germ cells; in parallel, both Müllerian (paramesonephric) and Wolffian (mesonephric) ducts coexist. The testicular pathway is triggered by the SRY gene on the Y chromosome, which upregulates SOX9 (with SF-1/NR5A1 and WT1) to drive Sertoli cell differentiation. Sertoli cells secrete AMH (MIS) causing Müllerian regression, and organize testis cords; Leydig cells (under SF-1) produce testosterone that stabilizes Wolffian ducts into epididymis, vas deferens, and seminal vesicles. Peripherally, 5-α-reductase converts testosterone to DHT for external genital masculinization (penis, scrotum, prostate)—a downstream step that explains why some DSDs have male internal ducts but undervirilized externals. In the ovarian pathway (no SRY), the default is not “passive”: WNT4/RSPO1 → β-catenin and FOXL2 actively suppress testis genes, promote granulosa/theca differentiation, and allow Müllerian ducts to persist (uterus, tubes, upper vagina) while Wolffian ducts regress in the absence of testosterone. Remember the timeline: gonadal commitment ~week 7; ductal outcomes follow AMH/testosterone signals; external genitalia finalize through DHT across the first/second trimesters. High-yield DSD correlations cement the pathways. 46,XY complete gonadal dysgenesis (Swyer syndrome)—SRY/SOX9/SF-1 axis failure—yields streak gonads, absent AMH/testosterone, female internal/external phenotype with primary amenorrhea and high gonadoblastoma risk. 46,XY androgen insensitivity (CAIS)—androgen receptor defect—produces testes with AMH (so no Müllerian structures) but female external phenotype and scant/absent pubic hair. 5-α-reductase deficiency (46,XY)—testosterone made, but poor DHT—leads to ambiguous or female-appearing externals at birth with virilization at puberty (T surge). Mixed gonadal dysgenesis (often 45,X/46,XY mosaicism) shows asymmetric gonads and variable ducts/phenotype. On the 46,XX side, congenital adrenal hyperplasia (21-hydroxylase deficiency) floods the fetus with androgens—virilized external genitalia but normal female internal organs (no AMH). WNT4 or RSPO1 mutations (46,XX testicular/ovotesticular DSD) push varying degrees of testis development. Turner syndrome (45,X) causes streak gonads, primary ovarian failure, and retained Müllerian structures. Exam pearls to memorize: SRY→SOX9 = testis; WNT4/FOXL2 = ovary. AMH dictates Müllerian fate, testosterone preserves Wolffian, DHT sculpts external male genitalia. A female phenotype with absent uterus suggests AMH present (e.g., CAIS); ambiguous external genitalia with uterus present points toward androgen excess in 46,XX (CAH). Map genotype → gonad → hormones → internal ducts → external genitalia, and nearly every Step 1 vignette falls into place. #USMLEStep1 #Embryology #GonadalDifferentiation #SRY #SOX9 #WNT4 #FOXL2 #AMH #Testosterone #DHT #Wolffian #Mullerian #DSD #SwyerSyndrome #AndrogenInsensitivity #5AlphaReductaseDeficiency #CAH #MedicalEducationUSA #Step1Prep #USMLEVideos