Reproductive Physiology I: Sexual Differentiation (MED310A Past Paper PDF)

Reproductive physiology I Differentiation of the reproductive systems (sexual differentiation) https://hectorarita.files.wordpress.com/2011/11/x_y.jpg Dr. Ann Dorward [email protected]  Learning seque...

Reproductive physiology I Differentiation of the reproductive systems (sexual differentiation) https://hectorarita.files.wordpress.com/2011/11/x_y.jpg Dr. Ann Dorward [email protected]  Learning sequence: Nov 13 Differentiation of the reproductive systems (sexual differentiation) Nov 15 Female reproductive physiology Nov 18 Male reproductive physiology Nov 20 Physiology of intercourse and conception Nov 22 (no class) Nov 25 Pregnancy and parturition (birth) Nov 27 Lactation (breastfeeding) and contraception strategies Dec 2 Optional review session Nov 19-20 Reproductive physiology lab in the HSc Dec 9 - Final exam for all MED310A content Perpetuation of the human species requires sexual reproduction: https://slideplayer.com/slide/9305391/ The male or female reproductive system has multiple sex-specific components: Primary reproductive organs that generate gametes (the gonads) A reproductive tract for delivery of the gametes Accessory sex glands that primarily produce secretions to support the gametes and the sex act (intercourse) Male vs female reproductive systems (posterior view) Female; Fig 18-2b Male; Fig 18-1b  Genetic sex specifies phenotypic sex: Conception ! (genetically unique individual, 2n=46 chromosomes Determination of genetic sex of an embryo (Chr XX or Ch XY) is dictated by the which chromosome the sperm delivers Embryonic window for sex specification starts at 6 wks of gestation (of 38 wks) https://www.thoughtco.com/homologous-chromosomes-definition-373469 chromosomes) (humans have 46 Chromosome spreads (karyotypes) help illustrate the human genetic complement https://www.dnalc.org/view/15562-Human-chromosomes-karyotype-colored-.html  Inheritance of a Chr XX or Chr XY combination is the foundation of sexual determination (the genetic sex) Fig 18-4: Summary of events in male vs female sexual differentiation (upper panel)  However, the early human embryo is not sexually “specified” From conception to week 6 of embryonic development, a male or female embryo is internally and externally identical in terms of the reproductive system The early embryonic gonad is unspecified (undifferentiated) and bipotential (waiting for signals) Both female (Müllerian) and male (Wolffian) early reproductive tracts are present in the embryo Undifferentiated reproductive system in the early human embryo (Figure 18-6, upper panel)  Genetic sex dictates gonadal sex Chr Y has few protein-coding genes, but the SRY transcription factor (Sex-determining gene of the Y chromosome) is essential for establishment of male gonadal sex (testis, plural testes) at week 7 of embryonic development Chr Y: one copy of the SRY gene In the absence of the SRY transcription factor, a different signaling pattern ensues to determine the female gonadal sex (ovary, plural ovaries)  Fig 18-4: Summary of events in male vs female sexual differentiation (establishment of gonadal sex)  Internal reproductive tracts are differentiated after the gonads (androgens (absence of + MIF (AMH) from androgens + MIF the testes permits signal Müllerian duct Wolffian duct development in development the female in the male embryo) embryo) Fig 18-6, 5th ed.  [Historical aside]: Where did these names come from? Johannes Peter Müller (1801- Caspar Friedrich Wolff: 1858), a pioneering German described the mesonephros and physiologist and comparative its ducts in his dissertation in anatomist 1759  Fig 18-4: Summary of events in male vs female sexual differentiation (lower panel) (androgenic steroids) (MIF = a protein hormone)  Androgens (testosterone, dihydrotestosterone (DHT)) and MIF (AMH) support development of the male reproductive tract and external male genitalia embryonic testis Mullerian Inhibitory factor (MIF) = Antimullerian hormone (AMH) https://www.ncbi.nlm.nih.gov/books/NBK279001/  “What is the [phenotypic] sex of our baby?” https://www.mdedge.com/pediatrics/article/237698/neonatal- medicine/preterm-infant-supine-sleep-positioning-becoming-more  External genitalia are differentiated after the gonads during human development https://www.glowm.com/ultrasoundAtlas Clinical ultrasound scans to disclose fetal sex to parents, typically taken at 18-22 weeks  (normal) human sex specification sequence: Sex-specific Genetic sex Gonadal sex Phenotypic sex hormone profiles CONCEPTION! Differentiation of 6-7 wks 7-9 wks external genitalia (moment of fertilization) evident by 10-12 wks * * Maturation of sex-specific reproductive tract and external genitalia continues until birth Embryology terms relevant to the development of female and male external genitalia (Figure 18-5, upper panel)  Dihydrotestosterone (DHT) is essential for development of the male external genitalia (Fig 18-5  Animated illustrations: female vs male external genitalia (gestation week 9-12) https://embryology.med.unsw.edu.au/embryology/imag es/a/a7/Female_external_001.mp4 https://embryology.med.unsw.edu.au/embryology/imag es/e/e2/Male_external_001.mp4  Ovaries remain in the abdominal cavity; testes descend into the scrotum under the influence of androgens: https://www.ncbi.nlm.nih.gov/books/NBK279001/ Gub = gubernaculum (ligament) 97% of male newborns have descended testes; remainder within 3 months post birth  (abnormal) human sex specification sequence: Sex-specific Genetic sex Gonadal sex Phenotypic sex hormone profiles  Differences in sexual development (DSDs) occur when the key signals are insufficient, absent or in excess: Absent SRY transcription factor Female development signaling in a male embryo (ovaries, tract, genitalia) Absent Androgen receptor Male testes; female (steroid hormone receptor) in physical appearance with a male embryo breast development Male testes and Insufficient testosterone to reproductive tract; female DHT conversion in a male embryo external genitalia Excessive androgen production Female ovary; male- (adrenal gland) in a female embryo differentiation of the reproductive tract and genitalia  Societal movement away from “Disorders of sexual differentiation” to “Differences in sexual differentiation” (DSDs) Differences are not necessarily disorders; subject of debate – who chooses? Health risk assessment for immediate medical management (life threatening conditions related to hormone imbalance for example) Infants born intersex; ethical and legal debate of gender self-determination vs parental influences at birth  Learning objectives: The difference between genetic sex, gonadal sex and phenotypic sex Reproductive features of the sexually undifferentiated human embryo Events leading to male embryo sexual differentiation (gonad, tract and external genitalia) Events leading to female embryo sexual differentiation (gonad, tract and external genitalia) Reproductive features of the sexually differentiated embryo/ fetus/ newborn  Sherwood & Ward Human Physiology, 5th edition Ch 18. p 723-731