L7

Question 1

Define gender

Answer 1

“the concept held by an individual (or those raising the individual) that they are male, female or ambivalent

Question 2

Contrast genetic sex, gonadal sex, and phenotypic sex

Answer 2

1. Genetic sex: chromosomal lvl e.g. 46, XX; 46XY
2. Gonadal: individuals sex organs (determined base don organs that are present) aka primary sex characteristics
3. Phenotypic sex: external genitalia aka secondary sex characteristics e.g. breasts

Question 3

What is SRY

Answer 3

Sex-determining region Y (SRY) AKA testis-determining factor (TDF), is a protein encoded by the SRY gene that is responsible for the initiation of male sex determination in humans.

Question 4

What is Turner’s Syndrome? Descibre the frequency, symptomology and effects on fertility. How is it detected?

Answer 4

• 45,XO

Frequency: Relatively common sex chromosome abnormality; 1 in 2500 female births

Distinctive physical features:
- Short stature, ptosis, low posterior hairline

Fertility: Most are infertile

Detection:

• No differences in infancy (emerge in childhood)
• FSH surge in newborns indicates ovarian failure
• Estrogen therapy initiated at age ~12

Question 5

What is Klinefelter Syndrome? Descibre the frequency, symptomology and effects on fertility. How is it detected?

Answer 5

47,XXY

Frequency: Most common sex chromosome abnormality; 1 in 500 male births
- Fewer than 26% are diagnosed

Symptomology:

• No obvious facial dysmorphology
• Tall stature
• Small testes
• Gynecomastia in late puberty
• Broad hips
• Sparse body hair
• Androgen deficiency, low serum T levels
• Elevated gonadotropins
• Azoospermia
• Psychiatric disorders more common
• Recent incentives encourage diagnosis so proper lifelong treatment can be administered

Fertility: 95-99% of males with KS are infertile

Question 6

What is Tripe X Syndrome? Describe the frequency, symptomology and effects on fertility. How is it detected?

Answer 6

47, XXX

Frequency: Common sex chromosome abnormality; 1 in 1000 female births
-Most undiagnosed

Symptomology:

• May be taller than average
• May result in kidney failure/disorders or seizures (~10%)
• May cause developmental delays (speech, language and motor skills)
• Most often there are no unusual physical features
• Normal sexual development

Fertility: Fertility is normal

Question 7

TDF absent for >9 weeks = _______

Answer 7

Testicular differentiation factor absent for > 9 weeks = female development

Question 8

Gonadal development determines phenotype based on

Answer 8

endocrine and paracrine secretions produced by the gonad

Question 9

Describe gonadal development in fetus

Answer 9

1. During the 5th week inside early embryo, primordial germ cells will migrate to urogenital ridges. Primordial germ cells will become ovarian follicles or initiate spermatogenesis.
2. The primordial gonad is undifferentiated and can turn into male or female sex organs.
   In females, the medulla will regress and the cortex will thickens. The germ cells will differentiate into primary oocytes.
   In males, the medulla will expand and the cortex recedes. Germ cells will migrate to cortex and differentiate into spermatogonia (pre sperm cells). Leydig cells will produce T and DHT (important for development of secondary sex characteristics). Sertoli cells will produce anti-Mullerian hormone, important for continuation of male development.

Question 10

Describe development of internal genitalia

Answer 10

Early in embryogenesis it is an undifferentiated duct system. Initially both wolffian and mullerian tubes are present. As development occurs, one of the structures will be degenerated. Wolffian duct will go on to give rise to male reproductive structures. Mullerian duct will go on to give rise to female reproductive structures.

Males: Leydig cells will produce T and DHT. Androgen production by Leydig cells will promote WOLFFIAN development. Sertoli cells will secrete AMH which promotes degeneration of mullerian tubes that would’ve otherwise formed female structures. Thus development of TESTES, degeneration of MULLERIAN duct, and continued development of WOFFIAN duct.

Females: Differentiation into OVARIES, degeneration of WOLFFIAN duct, continued development of MULLERIAN

Question 11

What is androgen receptor deficiency and associated problems?

Answer 11

DISORDER W/SEXUAL DEVELOPMENT (INTERSEX) that results in the partial or complete inability of the cell to respond to androgens. No problem with production of androgen but problem with androgen receptor.
- Leads to incomplete development of BOTH male and female structures. Wolffian and mullerian structures degenerate and there is female external genitalia.

Question 12

Discuss the contributions of endocrinologist Alfred Jost

Answer 12

Showed in rabbits that develop of female genitalia/reproductive structures is developed in absence of SRY and AMH (required to get mullerian duct degeneration and wolffian development).

Question 13

Results of early castration in rabbits?

Answer 13

Early castration in males: MULLERIAN development

Early castration in females: MULLERIAN development

Unilateral early castration in males: One side with testes and wolffian development, other side with mullerian duct development

Early castration in males and testosterone: Both mullerian and wolffian development

Testosterone-treated females: Ovaries, wolffian and mullerian duct development

Question 14

Using a flow diagram, show the normal sex development in genetic males 46, XY and genetic females 46, XX

Answer 14

Slide 11

Question 15

Describe the development of external genitalia

Answer 15

• External genitlia in the undifferentiated state is called cloaca (week 4). Cloaca go on to become both urinary and reproductive structures.
• VESICLE of cloaca go on to become URINARY BLADDER.
• PELVIC region: in females = URETHRA and in males, PROSTATIC URETHRA
• PHALLIC REGION: in females = vagina, in males = penile urethra (part of urethra that passes thru glans penis).

Question 16

What is 5a-reductase deficiency associated with?

Answer 16

5 a reductase converts T into DHT. DHT is required for male external structures. Deficiency can lead to a combo/mix of both male and female reproductive structures. Often raised as female. Shows DHT important esp for development of external structures

Question 17

Who are intersex individuals?

Answer 17

Individuals with variations in sexual characteristics including chromosomes, gonads, sex hormones or genitals that “do not fit the typical definitions of male of female bodies”

Question 18

Frequency of intersex individuals?

Answer 18

Collectively, as high as 1:300 births

Question 19

Describe the Prader scale of virilization of the external genitalia

Answer 19

Virilization is becoming male

1. No virilization: normal female anatomy
2. Stage 1: extension of glans clitoris, same internal structure
3. Stage 2
4. Stage 3
5. Stage 4
6. Stage 5: fully formed penis with urethra but internal structures still female
   - newborns at this stage are assumed 46 XY males

If there was stage 6 it would be normal male internal and external structures

Question 20

What is sexual dimorphism? Describe possible differences between the “male” and “female” brain

Answer 20

Sexual dimorphism is the condition where the 2 sexes of the same species exhibit diff characteristics beyond the differences in their sexual organs

2 main differences btwn sexes in human brain.

1. Sexually dimorphic nuclei:
   INAH3 is part of pre-optic hypothalamus. Development of this area is influenced by gonadal steroids. Since gonadal steroids higher in males, males have larger INA3.
2. Connections in the brain (cognitive/neurological differences):
   - Females have more INTRA (w/in) hemispheric connections while males have more INTER (across) hemispheric connections.