12 – Sex Determination Flashcards

1
Q

Sex of the individual is determined by

A
  • Sperm (+/- Y) and subsequent genetic control of sex differentiation
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2
Q

What cells are put aside for formation of the germ line?

A
  • A population of epiblast cells=PGCs
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3
Q

Primordial germ cells (PGCs)

A
  • Displaced from embryonic disk to the definitive yolk sac and part of the allantois
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4
Q

PGC migration

A
  • Into hindgut and towards GONADAL ridge
  • E-cadherin (membrane adhesion protein) help keep them grouped together
  • Integrins (membrane receptors) promote interaction of extracellular environment for migration to proceed
  • *remain PGCs outside GONADAL ridge area=die
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5
Q

Somatic cells around the PGCs

A
  • Secrete CHEMOATTRACTANTS
    o PGCs have receptors for them to induce their migration
  • Produce SURVIVAL FACTORS to maintain PGC viability during migration
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6
Q

Gonadal ridge

A
  • *bipotential gonad in most individuals (can become ovary or testes)
  • Forms medial to embryonic kidneys (mesonephros)
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7
Q

What are the origins of gonadal ridge cells (somatic)?

A
  • Local mesenchymal cells
  • Coelomic epithelium
  • Cells from mesonephric tubules
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8
Q

Degenerating mesonephric tubule cells form

A
  • Compact strands of tissue=PRIMITIVE SEX CORDS to incorporate PGCs
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9
Q

PGCs that enter gonadal ridge

A
  • Undergo major MORPHOLOGICAL and BIOLOGICAL changes (regardless of XX or XY)
  • *signals from somatic cells inducing switch from PGC to more germ-like cells to proceed to sperm or oocyte development
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10
Q

Phenotypic sex is largely governed by

A
  • Type of gonad that develops in the embryo
  • *determined by chromosome complement or genetic sex (+/- Y chromosome)
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11
Q

Gonads will produce sex-specific hormones leading to

A
  • Development of internal genitalia, secondary sex characteristics and external genitalia
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12
Q

Need for regulation of determination, differentiation and development of gonads

A
  • TIGHTLY regulated network of transcription factors and cell signalling molecules
  • *otherwise disorders of sex development (DSDs) occurs
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13
Q

Y chromosome contains a gene called

A
  • Sex Determining Region on Y chromosome (SRY)
  • *encodes SRY protein (testis determining factor(TDF))
  • **GENETIC SEX DIFFERENTIATION
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14
Q

What are the critical testis-determining genes?

A
  • SRY: when transcription reaches threshold = induces expression of Sox9
  • Sox9: Only high in males (sexually dimorphic)
  • *SRY->Sox9->Sertoli cell differentiation
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15
Q

Development of seminiferous cords

A
  • Solid tubes containing germ cells
  • Contain 15-10 coelomic derived cells(Sox9 positive cells)=Sertoli cells
    o Surround a central core of PRO-SPERMATOGONIA (gonocytes)
  • Mesenchymal cells and mesonephric cells between cords=Leydig or Interstitial cells
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16
Q

Sertoli cells orchestrate male-specific processes

A
  • Secretion of morphogens=Leydig Cells (will produce testosterone=drive toward phenotypic sex of individual)
17
Q

At puberty, seminiferous cords become

A
  • Seminiferous tubules=continuation between rete testis and efferent ducts
18
Q

Mesonephric duct develops into

A
  • Epididymis
  • Ductus deferens
19
Q

Efferent ducts, epididymis and ductus defers are part of

A
  • Excurrent extragonadal duct system
  • *carry sperm through to urethra
20
Q

Cells without SRY express

A
  • Female promoting genes and INHIBIT male promoting genes (ex. inhibit Sox9)
  • **ovarian development LACKS A SINGLE GENETIC SWITCH
    o Key genes do exist for correct development
21
Q

Forkhead box L2 (Foxl2)

A
  • Gene transcription factor
  • One of earliest to be induced in developing female-specific ovary
  • *mutation in goats leads to female to male sex reversal
22
Q

Foxl2 in postnatal life

A
  • Maintenance of ovary by suppressing genes involved in testis determination from embryonic to adult life
23
Q

Without SRY protein, some cells of degenerating sex cords and coelomic cells surround the PGCs (oogonia) and differentiate into

A
  • Primitive follicular or pre-granulosa cells
24
Q

Mesonephric duct is still intact early and will begin (ovary development)

A
  • Regressing while rete tubules degenerate
  • *NO DIRECT DUCT OUTLETS for gametes like in male
  • *paramesonephric duct develops further and ENLARGES
25
Q

Primitive follicular cells surround PGCs (ovary development)

A
  • Do NOT penetrate deeply into interior of developing ovary
  • *STAY ORGANIZED as primordial follicles in periphery (will become the cortex)
  • Sex cords disappear completely
26
Q

What does the paramesonephric duct become once it has enlarged greatly with an opening

A
  • Future INFUNDIBULUM
  • Fuse together near attachment with urogenital sinus
    o Degree of fusion leads to UTERINE TYPES (ex. duplex, bicornuate, simplex)
27
Q

XX oocyte in developing follicle produces

A
  • Growth Differentiation Factor 9 (GDF9)
    o Induces granulosa cells to secrete morphogens to stimulate gene specific thecal cell programming
28
Q

Thecal cells

A
  • Will produce androgens under LH control, to be converted into estradiol within granulosa cells
29
Q

Granulosa cells orchestrate female-specific processes

A
  • Signals germ cells to enter meiosis
  • *Secretes morphogens that induce Thecal cells (steroidogenic)
30
Q

Interplay of testis and ovary pathways

A
  • Male and female sex differentiation pathways ACTIVELY SUPPRESS one another
    o During gonad differentiation and after testes or ovaries have developed
  • Studies have show that testes and ovaries are EASILY CONVERTED
    o CONSTANT EXPRESSION of specific genes is needed to prevent trans differentiation
31
Q

DSDs: sex reversal species

A
  • Seen in dogs, horses, pigs and goats
  • Pigs and goats have high frequency compared to other species
  • Ex. polled intersex syndrome in goats
32
Q

Polled intersex syndrome in goats

A
  • Due to DELETION within chromosome 1 that DIRECTLY effects transcription of 2 genes
    o Hornlessness (Polled): dominant
    o Ovarian development (Foxl2)
33
Q

Polled intersex syndrome in goats: heterozygous polled genetic male (XY)

A
  • No horns
  • Sex determination=male (SRY is present)
  • **Phenotypic male
34
Q

Polled intersex syndrome in goats: homozygous polled genetic female (XX)

A
  • No horns
  • Infertile (no SRY) phenotypic male
  • *female to male reversal
35
Q

Polled intersex syndrome in goats: heterozygous polled genetic female (XX)

A
  • No horns
  • Still have one good copy of Foxl2
  • *phenotypic female