Sex Differentiation

Question 1

What is the sequential process of sexual differentiation?

Answer 1

1. Establishment of genetic sex
2. Translation of genetic sex into gonadal sex
3. Translation of gonadal sex into phenotypic sex

Question 2

What are the 3 components of the female tract?

Answer 2

Oviduct, uterus and upper vagina

Question 3

What are the 3 components of the male tract?

Answer 3

Epididymis, vas deferens and seminal vesicle

Question 4

What are called the urogenital sinuses (common primordium for external genitalia) in females? and males?

Answer 4

Females: clitoris, vulva
Males: penis, scrotum

Question 5

Are the testes essential for male sexual differentiation?

Answer 5

yes!

Question 6

Are ovaries essential for female differentiation?

Answer 6

no!

Question 7

What was Alfred Jost’s 1940 experience about?

Answer 7

He removed the undifferentiated testes from male rabbit embryos, and found that they developed a female reproductive tract and female genitalia. Gonadectomised female embryos also developed female features.

Question 8

Describe the pathway from the undifferentiated state to female or male differentiation.

Answer 8

Differentiation to female is a default pathway, mainly hormone independent, as the male pathway is hormone dependent, with male determining switches.

Question 9

What are the pre-requisites for normal sex differentiation?

Answer 9

• Normal intact chromosome complement
• Fully functioning sex determination genes
• Intact steroidogenic pathways and receptors
• Default option is female pathway

Question 10

What is sexual differentiation for in both males and females?

Answer 10

Males: provision of sperm
Females: Provision of eggs, internal fertilization, pregnancy, lactation

Question 11

Classifications of sexual differences (7) for male and female

Answer 11

• Chromosomal: XY (m), XX(f)
• Gonadal: Testis (m), ovary (F)
• Internal ducts: Wolffian-epididymis, vas deferens (m), mullerian - uterus, oviduct (f)
• External genitalia: penis, scrotum (m), clitoris vulva (f)
• Phenotypic: shoulders, muscle (m), hips, fat (f)
• Behavioural: “male” (m), “female” (f)
• Legal: On birth certificate (both)

Question 12

What is the male phenotype?

Answer 12

It is the presence of Y

Question 13

How does sexual reproduction produce new combinations of genes?

Answer 13

The sperm from the male and the egg from the female give one chromosome each, these chromosomes exchange genes during crossing-over at meiosis to produce gametes, this produces a new combination of genes on each chromosome

Question 14

What is the sry gene?

Answer 14

Sex determining Region of Y chromosome

Question 15

What is the SRY gene’s role?

Answer 15

They inserted the SRY gene in a XX egg, which gave a female rat with phenotypic male with testes and external male genitalia

Question 16

What are mis-pairings?

Answer 16

SRY gene transferred to X, sperm with X and SRY gene= fertilization by this sperm would produce an XX male!
Y chromosome can also have an abnormal SRY, causing a XY female.

Question 17

How does SRY protein work in DNA?

Answer 17

It binds to DNA because of its high mobility group (HMG) proteins, inducing transcription of other genes.

Question 18

What does the DAX1 on X chromosome does?

Answer 18

it inhibits testicular development

Question 19

What does SRY expression lead to?

Answer 19

It enhances the expression of other genes leading to AMH/MIS (Anti-mullerian hormone = Mullerian inhibiting substance: Produced by sertoli cells)

Question 20

What does the differentiation of gonads by SRY/SOX9,3 result in ?

Answer 20

It results in Sertoli cells producing AMH and Leydig cells producing testosterone

Question 21

What does the AMH (Anti-Mullerian hormone) once secreted by the testis?

Answer 21

It suppresses the Mullerian duct development, which leads to the absence of the uterus, no oviduct.

Question 22

What else do the testis secrete?

Answer 22

They secrete testosterone, which leads to the development of the Wolffian duct, which gives way to the vas deferent and the epididymis.

Question 23

What else does testosterone do in terms of external genitalia (male and female)?

Answer 23

Testosterone stimulates the development of male external genitalia in the form of DHT (dihydrotestosterone). In the absence of testosterone, DHT cannot stimulate male external genitalia, so femal external genitalia is favored.

Question 24

What hormones are responsible for testicular descent and what are the steps called?

Answer 24

1. Trans-abdominal descent, with the presence of AMH
2. Inguino-scrotal descent, with the presence of testosterone
   Leading to testis in the scrotal position

Question 25

What characterizes a defect in testosterone synthesis or action? (e.g. Testicular feminization or androgen insensitivity syndrome)

Answer 25

- Phenotypic female (XY) - No ovaries (testes but infertile) - Blind ending vagina - -> testosterone synthesis or action defect leads to androgen insensitivity syndrome

Question 26

What is the androgen insensitivity syndrome?

Answer 26

Testosterone is still produced, but there is a lack in androgen receptors, causing female external genitalia, as well as no epididymis nor vas deferens.

Question 27

How to treat female phenotype (XY)?

Answer 27

Female phenotype (XY) are infertile (cryptorchidism), and the treatment is to surgically correct ambiguous genitalia = easier to construct functional vagina than penis. The surgery is called a gonadectomy, it is done post-puberty and E2 treatments are required after surgery.

Question 28

What characterizes the second problem that can overcome, Congenital adrenal hyperplasia (CAH)?

Answer 28

Masculinization of external genitalia at birth. It is the hyperplasia of the adrenal glands before birth, leading to excessive androgen production causing masculinization of genitalia (more obvious in females; labia tends to come together looking live a scrotum, clitoris enlarges to look like a penis)

Question 29

What happens in CAH females at a hormonal level?

Answer 29

Ovaries don't produce AMH hormones, maintaining the Mullerian duct (uterus, oviduct), and the adrenal gland stimulates testosterone production, and DHT further stimulates masculinization of external genitalia. Absence of SRY gene.

Question 30

What happens in CAH at a cellular level?

Answer 30

ACTH stimulates synthesis of androgens, which leads to masculinization of external genitalia. Cholesterol is the precursor for certain hormones, like aldosterone and cortisol, which require 21 hydroxylase. This enzyme is deficient in CAH, which leads to low aldosterone and cortisol production, reducing negative feedback onto hypothalamic-pituitary axis (stopping ACTH stimulation).

Question 31

How frequent is CAH and what gene is mutated?

Answer 31

it happens in 1:13000 in the general population. It happens when both copies of CYP21 are mutated.

Question 32

What is the treatment for CAH?

Answer 32

surgical correction at birth and raise them as girls (tendency towards male play patterns)

Question 33

What happens at a hormonal level for sexual differentiation of the brain?

Answer 33

Testis secrete testosterone, stimulating male external genitalia and sexual differentiation of the brain (E2)

Question 34

When does sexual differentiation of the brain occur?

Answer 34

It occurs during a critical time period during development. It varies from one specie to the next.

Question 35

What are certain neurological and psychiatric diseases that exhibit a sex difference in incidence?

Answer 35

``` Anorexia nervosa - 93:7 Bulimia - 75:25 Anxiety disorder - 67:33 Depression - 63:37 MS - 58:42 etc. ```

Question 36

What do MRIs indicate for differences between brain activity patterns between males and females?

Answer 36

Whole brain - larger in men Regions of the hypothalamus - larger in men Structures connecting the left and right brain - corpus callosum - posterior portion is larger and more bulbous in women etc.

Question 37

Name 3 sex differences in selected human behaviors and their effect sizes.

Answer 37

- Aggression: Moderate size effect - Childhood play (level of activity, degree of rough and tumble play, selection of toys and playmates): Moderate to large effect size - 3D visual rotation: Large (men>women)

Question 38

True or false: in female, estradiol produced by fetal ovary can cross the blood-brain barrier.

Answer 38

False! it can't cross the BBB

Question 39

How does LH/FSH control work after puberty in the brain?

Answer 39

Female retain surge center and tonic center to control Lh/FSH after puberty.

Question 40

How do sex determining factors work in males?

Answer 40

XY chromosomal pair: start with the Testis determining factor (TDF) = testes develop = Sertoli cells secrete AMH = AMH causes leydig cells to differentiate = testosterone and DHT release, each stimulation development of male duct system and development of penis, scrotum and accessory sex glands. AMH also = degeneration of paramesonephric duct.

Question 41

How do sex determining factors work in females?

Answer 41

XX chromosomal pair: starts with the absence of TDG = ovaries develop = no AMH = paramesonephric ducts become the oviducts, uterus, cervix and part of the vagina = complete female tract.