Flashcards in Sex Differentiation Deck (41):
What is the sequential process of sexual differentiation?
1. Establishment of genetic sex
2. Translation of genetic sex into gonadal sex
3. Translation of gonadal sex into phenotypic sex
What are the 3 components of the female tract?
Oviduct, uterus and upper vagina
What are the 3 components of the male tract?
Epididymis, vas deferens and seminal vesicle
What are called the urogenital sinuses (common primordium for external genitalia) in females? and males?
Females: clitoris, vulva
Males: penis, scrotum
Are the testes essential for male sexual differentiation?
Are ovaries essential for female differentiation?
What was Alfred Jost's 1940 experience about?
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.
Describe the pathway from the undifferentiated state to female or male differentiation.
Differentiation to female is a default pathway, mainly hormone independent, as the male pathway is hormone dependent, with male determining switches.
What are the pre-requisites for normal sex differentiation?
- Normal intact chromosome complement
- Fully functioning sex determination genes
- Intact steroidogenic pathways and receptors
- Default option is female pathway
What is sexual differentiation for in both males and females?
Males: provision of sperm
Females: Provision of eggs, internal fertilization, pregnancy, lactation
Classifications of sexual differences (7) for male and female
- 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)
What is the male phenotype?
It is the presence of Y
How does sexual reproduction produce new combinations of genes?
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
What is the sry gene?
Sex determining Region of Y chromosome
What is the SRY gene's role?
They inserted the SRY gene in a XX egg, which gave a female rat with phenotypic male with testes and external male genitalia
What are mis-pairings?
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.
How does SRY protein work in DNA?
It binds to DNA because of its high mobility group (HMG) proteins, inducing transcription of other genes.
What does the DAX1 on X chromosome does?
it inhibits testicular development
What does SRY expression lead to?
It enhances the expression of other genes leading to AMH/MIS (Anti-mullerian hormone = Mullerian inhibiting substance: Produced by sertoli cells)
What does the differentiation of gonads by SRY/SOX9,3 result in ?
It results in Sertoli cells producing AMH and Leydig cells producing testosterone
What does the AMH (Anti-Mullerian hormone) once secreted by the testis?
It suppresses the Mullerian duct development, which leads to the absence of the uterus, no oviduct.
What else do the testis secrete?
They secrete testosterone, which leads to the development of the Wolffian duct, which gives way to the vas deferent and the epididymis.
What else does testosterone do in terms of external genitalia (male and female)?
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.
What hormones are responsible for testicular descent and what are the steps called?
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
What characterizes a defect in testosterone synthesis or action? (e.g. Testicular feminization or androgen insensitivity syndrome)
- Phenotypic female (XY)
- No ovaries (testes but infertile)
- Blind ending vagina
--> testosterone synthesis or action defect leads to androgen insensitivity syndrome
What is the androgen insensitivity syndrome?
Testosterone is still produced, but there is a lack in androgen receptors, causing female external genitalia, as well as no epididymis nor vas deferens.
How to treat female phenotype (XY)?
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.
What characterizes the second problem that can overcome, Congenital adrenal hyperplasia (CAH)?
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)
What happens in CAH females at a hormonal level?
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.
What happens in CAH at a cellular level?
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).
How frequent is CAH and what gene is mutated?
it happens in 1:13000 in the general population. It happens when both copies of CYP21 are mutated.
What is the treatment for CAH?
surgical correction at birth and raise them as girls (tendency towards male play patterns)
What happens at a hormonal level for sexual differentiation of the brain?
Testis secrete testosterone, stimulating male external genitalia and sexual differentiation of the brain (E2)
When does sexual differentiation of the brain occur?
It occurs during a critical time period during development. It varies from one specie to the next.
What are certain neurological and psychiatric diseases that exhibit a sex difference in incidence?
Anorexia nervosa - 93:7
Bulimia - 75:25
Anxiety disorder - 67:33
Depression - 63:37
MS - 58:42
What do MRIs indicate for differences between brain activity patterns between males and females?
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
Name 3 sex differences in selected human behaviors and their effect sizes.
- 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)
True or false: in female, estradiol produced by fetal ovary can cross the blood-brain barrier.
False! it can't cross the BBB
How does LH/FSH control work after puberty in the brain?
Female retain surge center and tonic center to control Lh/FSH after puberty.
How do sex determining factors work in males?
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.