01. Puberty and Sex Differentiation

• gonads = organ that produces gametes (ovary or testis)
• gamete = male/female mature reproductive cell with a haploid set of chromosomes
• germ cell = sperm or oocyte or their developmental precursors
• primordial germ cells are sexually indifferent until week 7
• primordial germ cells migrate to a region of the dorsal wall that will form the gonads, guided by chemotaxis

  • genital ridges secrete factors that attract the primordial germ cells
• Y chromosome is small so doesn't encode enough genes for male development, so must encode a controller gene
• from week 7 onwards the fetus becomes sexually different
• SRY = region of Y chromosome that leads to male development

  • SRY transcription factor
• testis development:

  • columns of cells from coelomic epithelium proliferate and penetrate deeply to form the primitive sex cords
  • these express SRY - sertoli cells
  • PGCs arrive from their migration
  • associate with primitive sex cords to form seminiferous tubules
  • leydig cells are another important somatic cell that is present
• testis structure:

  • within the seminiferous tubules are prospermatogonia (used to be primitive germ cells) and sex cord cells which form sertoli cells
  • between the seminiferous tubules is vasculature and clusters of leydig cells
• female development is also called the default pathway

  • sex cord cells don't penetrate deeply as they don't express SRY
  • cluster around primitive germ cells and form primordial follicles
  • granulosa and theca cells
• turner syndrome is where you are missing one of your X chromosomes

  • eggs die off quickly
  • ovaries don't form properly as there are no normal germ cells
• male development weeks 8-12

  • androgen production by leydig cells maintain wolffian ducts
  • mullerian inhibitory substance produced by sertoli cells to cause regression of mullerian ducts
• female development weeks 8-12

  • mullerian ducts
• undifferentiated external genitalia has three key structures

  • genital tubercle
  • urogenital fold
  • labio-scrotal swelling
• for males , DHT acts on external genitalia to cause genital tubercle to develop into a penis

  • uro-genital fold forms spongy urethra
  • labio-scrotal swelling forms scrotal sac
• for females, external genitalia forms:

  • genital tubercle = clitoris
  • labio-scrotal swelling = labia majora
  • uro-genital fold = labia minora
• defining puberty

  • males = first ejaculation
  • females = first menstruation
• HPG axis = hypothalamus, pituitary, gonads
• hypothalamus produces gonadotropin releasing hormone which enters blood stream and stimulates production of FSH and LH at the pituitary
• kisspeptin 1 is encoded by the KISS1 gene

  • exogenous kisspeptin induces puberty
  • kisspeptin pulses match GnRH pulses
  • expression rises in puberty
• FSH and LH act on the gonads

  • ovaries produce oestrogen and progesterone which inhibit the pituitary production of FSH and LH
  • testis produce inhibin and testosterone which inhibit the pituitary production of FSH and LH
• sex steroids are produced from cholesterol and have three families

  • progestogens - pregnancy
  • androgens - maleness
  • oestrogens - femaleness
• for males all secondary sexual characteristics are caused by testicular androgens
• for females and secondary sexual characteristics:

  • ovarian oestrogens lead to growth of breasts and genitalia
  • ovarian and adrenal androgens lead to growth of pubic and axillary hair
• rising levels of sex hormones during puberty lead to growth hormone regulating growth plates growing

  • once sufficient oestrogen levels are reached the growth plates fuse
  • maximum adult height