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PHYS - REPRO > 1. SEXUAL DIFFERENTIATION & DETERMINATION > Flashcards

1. SEXUAL DIFFERENTIATION & DETERMINATION Flashcards

1
Q

*Define sexual determination

A
  • Sexual determination is the chromosomal determination as male or female. It is a genetically controlled process that’s dependent on the molecular switch of the Y chromosome
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2
Q

*Define Sexual differentiation

A
  • Sexual differentiation is the process by which the internal & external genitalia develop as male or female
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3
Q

What does the SRY gene do in gonadal development?

A
  • The SRY gene is the sex determining region of the Y chromosome
  • It is a molecular switch which is responsible for the development of the testes
  • The SRY gene switches on at week 7 on embryonic development
  • In the absence of the SRY gene, the ovaries develop
  • The testes produce AMH & testosterone
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4
Q

*What are the gonads & what is the precursor for gonads ?

A
  • The gonads are the ovaries in females & the testes in males
  • After fertilization, a pair of gonads form
  • The GENITAL RIDGE PRIMORDIA is the precursor for gonads
  • It is located on posterior wall of the lower thoracic lumbar region
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5
Q

What are the three main cell types that migrate to the genital ridge during gonadal development?

A
  • The genital ridge is the precursor for teh gonads
  • Three waves of cells invade the genital ridge during gonadal development
    1. PRIMORDIAL GERM CELLS - develop into spermatozoa (males) & oocytes (females)
    2. PRIMITIVE SEX CORDS - develop into Sertoli cells (males) & Granulosa cells (females)
    3. MESONEPHRIC CELLS _ develop into Leydig (males & the Theca cells (females)
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6
Q

** What happens during primordial germ cell migration?

A
  • At 3 weeks, a small cluster of diploid embryonic cells in the yolk sac expand by mitosis
  • These primordial germ cells then migrate to the genital ridge but they move through the connective tissue of the hindgut & region of the developing kidney first
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7
Q

***What are the primitive sex cords?

A
  • The primitive sex cords migrate inwards
  • The cells of the germinal epithelium which are located on the genital ridge will migrate inwards to form columns known as PRIMIITIVE SEX CORDS
  • In males these primitive sex cords will go on to develop Sertoli cells & Granulosa cells in females
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8
Q

*What do the primitive sex cords in males do?

A
  • The primitive sex cords in males develop into Sertoli cells
  • The primitive sex cords penetrate the MEDULLARY MESENCYME & surround the primordial germ cells (spermatozoa) to from the testis cord.
  • The testis cord is the precursor for the seminiferous tubules
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9
Q

What do the primitive sex cords in females do?

A
  • The primitive sex cords in females develop into Granulosa cells
  • The primitive sex cords in females are less well defined & don’t penetrate the medullary mesenchyme as deeply
  • The primitive sex cords form small clusters around the primordial germ cells (oocyte) which are the precursors for ovarian follicles
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10
Q

What do Sertoli cells in males do?

A
  • Sertoli cells develop from the primitive sex cords
  • The primitive sex cords express SRY which leads to the development of the testes
  • Sertoli cells express Anti-Mullerian Hormone (AMH) which causes the regression of the Mullerian duct
  • Located in the seminiferous tubules & are involved in spermatogenesis (primordial germ cells -> spermatozoa)
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11
Q

Where do mesonephric cells originate & what are they?

A
  • Mesonephric cells orginate from the MESONEPHRIC PRIMORDIUM lateral to the genital ridge
  • The mesonephric cells develop into the Leydig cells in males & Theca cells in females
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12
Q

*What do the mesonephric cells in males form?

A
  • The mesonephric cells in males act under the influence of pre-sertoli cells which express SRY & go on to develop:
    1. Vascular tissue
    2. Basement membrane
    3. Leydig cells
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13
Q

What do Leydig cells do?

A
  • Leydig cells develop form mesonephric cells
  • Leydig cells don’t express SRY but synthesize testosterone
  • Found in the spaces between the seminiferous tubules of the testes
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14
Q

What do the mesonephric cells in females from?

A
  • In females, there’s no SRY so without SRY expression the mesonephric cells form:
    1. Vascular tissue
    2. Theca cells - may go onto secrete androgens but not during embryonic development
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15
Q

What is the Mullerian duct?

A
  • The Mullerian ducts is involved in the development of internal female genitalia
  • Develops into uterus, uterine tubes & upper third of vagina
  • Females don’t have testes, so no Sertoli cells are produced therefore no AMH, allowing Mullerian duct to grow
  • No Leydig cells = no testosterone so no development of Wolffian duct
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16
Q

What is the Wolffian duct>

A
  • The Wolffian duct is responsible for development of male internal genitalia
  • The differentiation of the Wolffian duct is stimulated by testosterone into structures such as the vas deferens, seminal vesicles & part of the prostate
  • Sertoli cells of the testis produce AMH, causing regression of the Mullerian duct
  • Leydig cells produce testosterone which stimulates Wolffian duct differentiation
17
Q

What enzyme converts testosterone into dihydrotestosterone?

A
  • 5 alpha reductase converts testosterone into dihydrotestosterone in the genital skin. It uses NAPH to produce NADP & H+
  • 5 alpha reductase is also present in females, but the lack of testosterone means there’s no development of male genitalia
18
Q

What are the effects of DHt & how is it involved in external male genitalia formation?

A
  • Dihydrotestosterone (DHT) is more potent than testosterone but binds to the same receptor as testosterone
  • DHT is needed for teh formation of external genitalia in males:
    1. Clitoral area enlarges into penis
    2. Fusion of labia & become ruggated to from scrotum
    3. Prostate froms
19
Q

Describe the formation of external genitalia in males & females?

A
  1. GENITAL TUBERCLE:
    - > Males = Glans penis
    - > Females = Clitoris
  2. URETHRAL FOLD:
    - > Males = Penile urethra
    - > Females = Labia minora
  3. GENITAL SWELLING:
    - > Males = Scrotal swelling -> Scrotum
    - > Females = Labia majora
20
Q

*What are the three classes of sexual differentiation disorders?

A
  1. GONADAL DYSGENESIS - incomplete sexual differentiation leading to abnormal development of gonads
  2. SEX REVERSAL - Phenotype doesn’t match genotype, e.g genetically male but phenotypically female
  3. INTERSEX - ambiguous genitalia or components of both tracts (Mullerian & Wolffian)
21
Q

What happens in Androgen insensitivity syndrome?

A
  • Androgen sensitivity occurs when an individual produces testosterone but cannot respond to it, could be issues with receptor
  • So they are genotypically male but phenotypically female or ambiguous
  • It can be complete or partial depending on the extent of androgen insensitivity
  • XY = testes = sertoli cells & leydig cells
  • Sertoli cells produce AMH so Mullerian ducts regress
  • Leydgig cells produce testosterone but cannot respond to testosterone. No differentiation of Wolffian duct & no external male genitalia develops as DHT also binds to testosterone receptor
  • INTERNAL GENITALIA = NONE but testes present which don’t descend as there’s no formation of the scrotum
  • EXTERNAL GENITALIA = Female as default because testosterone cannot cause external male genitalia development
22
Q

What are the symptoms of Androgen insensitivity for diagnosis?

A
  • Primary amenorrhea & lack of body hair - no menstruation as there’s no development of the Mullerian duct
  • XY genotype but female phenotype with undescended testes
23
Q

What happens in 5 alpha reductase deficiency?

A
  • 5 alpha reductase is needed for the conversion of testosterone into DHT
  • A deficiency will mean that testosterone is produced but cannot be converted into DHT.
  • EXTERNAL MALE GENITALIA = female or ambiguous as DHT is needed for external male genitalia development
  • INTERNAL MALE GENITALIA = Male as Wolffian duct will be stimulated by testosterone & Mullerian duct will regress sue to AMH production by Sertoli cells
24
Q

What happens in Turner’s Syndrome?

A
  • Genotype = XO, missing one X chromosome
  • Internal genitalia = female & external genitalia = female
  • Can have ‘streak’ ovaries which are small or underdeveloped as two X chromosomes are needed for ovarian development
  • Uterus & tubes are present but there be other defects in growth & development
  • Mainly due to mosaicism , stage of development at which X was lost determines presentation
  • Loss of X in early stages = severe presentation but milder if only some cells don’t have an X chromosome
25
Q

Describe how the different steroid hormones are made?

A
  • Cholesterol is the precursor to the steroid hormones. It has 27 C with a carbon side chain
  • Cleavage of this side chain produces PROGESTAGENS (progesterone, pregnenolone) with 21C
  • These progestogens can be converted into glucocorticoids (cortisol) or mineralocorticoids (aldosterone) also with 21C
  • Cleaving 2C produces ANDROGENS with 19C
  • Cleaving 1C produces EOSTROGENS with 18C
  • CHOLESTEROL -> PROGESTAGENS -> CORTISOL or ANDROGENS -> ESTROGENS
26
Q

*What happens in Congenital adrenal hyperplasia ?

A

Congenital adrenal hyperplasia refers to a group of rare, inherited disorders where there’s a deficiency in the enzymes involved in making adrenal hormones including cortisol. It leads to enlargement of the adrenal gland

27
Q

What can happen to an XX embryo with congenital adrenal hyperplasia?

A
  • CAH could involve a defiency in 21 hydroxylase which is the enzyme involved in the conversion of progestagens into cortisol.
  • So a deficiency of this enzyme will lead to low cortisol levels, the low cortisol levels will stimulate an increase in CRH & ACTH due to negative feedback
  • The ACTH will cause rapid uptake of cholesterol into the adrenal gland & causes upregulation of P450 cc which cleaves the side chain of cholesterol
  • However, the progestagens produced as a result cannot be converted into cortisol & will therefore be converted into androgens
  • ## These androgens (testosterone & DHT) will lead to the masculinisation of the external genitalia
28
Q

What are the consequences of high levels of androgens due to congenital adrenal hyperplasia on an XX embryo?

A

XX = no AMH from Sertoli so Mullerian ducts remain

  • High levels of DHT cause external male genitalia development but the testosterone levels aren’t high enough to cause differentiation of the Wolffian duct
  • 21 hydroxylase can also lead to a lack of aldosterone which can lead to salt wasting

PHYS - REPRO (10 decks)

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