Repro L5 flashcards

What is sex determination vs differentiation

Determination: biological process that establishes if an organism develops as male or female

Differentiation: The phenotypic development of structures and characteristics due to hormones produced after gonadal determination.

 How many pairs of autosomes and sex chromosomes do humans have?

 22 pairs of autosomes and 1 pair of sex chromosomes (XX or XY).

Sex determined at fertilisation in humans

What makes the gonadal rudiment unique compared to other organ rudiments?

It is the only organ rudiment that can differentiate into two distinct organs — the ovary or the testis.

What is the bipotential stage

Embryo has no phenotypic sex and gonads can develop into either ovaries or testes

at around 7 weeks of gestation

At what stage are all embryos initially programmed toward?

The female developmental pathway, unless diverted by male-determining signals.

What are primordial Germ cells

precursors of sperm and oocyte - large spherical cells

appear outside embryo in yolk sac at 3 weeks of gestation

Form gonads at week 7 of gestation

undergo mitosis until week 10

decide sexual fate after entering gonads

How do PGCs migrate to gonads

via chemotactic signals such as TGFβ, SCF, and bFGF.

What are indifferent gonads

Early gonad present in both sexes before differentiation into ovary or testis

formed by proliferation of epithelium and mesenchyme on medial side of the mesenephros (genital ridge)

determined by genetic factors especially SRY on Y chromosome

What is the mesonephros

The foetal ‘interim’ kidney, located adjacent to the developing gonads.

primary vs secondary sex determination

primary - determines if gonads become testes or ovaries

secondary - development of secondary sexual characteristics, influenced by gonadal hormones

Jost paradigm

male differentiation is an active process dependent on testosterone and AMH produced by the testes.

Organism develops a female phenotype in absence of ‘male factor’

What are Müllerian ducts?

develop into female internal reproductive organs: uterus, oviducts, cervix, and upper vagina.

Maintained by The absence of AMH (regresses and dies in AMH presence)

Express AMH receptors - if they lack these, they can’t respond to AMH and mullerian ducts persist

What cells produce AMH and testosterone

AMH - sertoli cells

Testosterone - Leydig

What are Wolffian ducts?

Male internal reproductive organs: vas deferens, epididymis, and seminal vesicles.

maintained by testosterone

Wolffian ducts degenerate in females due to lack of testosterone

Have androgen receptors for testosterone

What happens if both AMH and testosterone are

The Wolffian ducts degenerate and Müllerian ducts persist, resulting in female internal structures.

 

What is the SRY gene

 A gene on the Y chromosome that triggers testis development; it encodes a transcription factor that acts as a genetic switch.

Expressed in sertoli cells and activates SOX9 and SF-1, initiating the male developmental pathway.

only needed early in gonadal development.

If absent, The gonad develops along the default ovarian pathway.

What does SOX9 do

An autosomal gene activated by SRY that induces testis formation; overexpression can cause testis formation even in XX individuals.

Promotes differentiation of sertoli cells and testis cord - induces AMH expression

If duplicated in XX embryo, it can lead to testis development even without SRY

What does SF-1 do

A transcription factor that, together with SRY, promotes AMH expression in Sertoli cells.

 

which genes influence ovarian development

RSPO1, WNT4, DAX1, and FOXL2 — they suppress testis-forming genes.

β-catenin (WNT4 pathway) - supports ovarian differentiation by inhibiting testis-promoting pathways.

What happens if WNT4 or RSPO1 are mutated?

Partial or complete sex reversal may occur due to inappropriate activation of testis pathways.

What is DAX1’s role in ovarian development?

It antagonizes the action of SRY and SOX9, helping maintain ovarian differentiation.

Disorders of Sex development

Conditions where the development of chromosomal, gonadal, or anatomical sex is atypical.

1. Sex chromosome DSDs (numerical/structural abnormalities)

2. 46,XX DSDs (chromosomal female with virilisation or male characteristics)

3. 46,XY DSDs (chromosomal male with undervirilisation or female characteristics)

 

Sex chromosome DSDs

Numerical or structural abnormalities of the sex chromosomes.

Ex.

Turner syndrome (45,X) - underdeveloped ovaries

Klinefelter syndrome (47,XXY) - extra chromosome = small testes, infertility, feminisation

Approximately 25% of conceptuses have a major chromosomal abnormality.

What is aneuploidy

A condition where cells have an abnormal number of chromosomes (not euploid).

caused by Nondisjunction

What is nondisjunction

— the failure of homologous chromosomes or sister chromatids to separate properly.

One gamete receives both chromosomes, while the other receives none, resulting in zygotes with trisomy or monosomy.

What is a 46, XX DSD

An individual with a normal female chromosome set (46,XX) but with virilisation or male-like characteristics.

caused by androgen excess during pregnancy. - Ex. Congenital Adrenal Hyperplasia (CAH).

Features: Enlarged clitoris, fused labia, ambiguous genitalia, but normal ovaries and female internal structures.

 

what is Congenital Adrenal Hyperplasia (CAH).

cause virilisation because enzyme defects (often 21-hydroxylase deficiency) lead to overproduction of adrenal androgens, masculinising the female fetus.

What is 46 XY DSD

An individual with a normal male chromosome set (46,XY) but incomplete masculinisation.

Caused by: Abnormal testis development, defects in androgen production, or androgen receptor defects. 

What is the result of incomplete testis differentiation? ( 46xy dsd)

Reduced AMH and testosterone → incomplete regression of Müllerian ducts and incomplete development of male ducts/genitali

Enzyme deficiencies in testosterone synthesis (e.g., 17β-hydroxysteroid dehydrogenase deficiency). causes defective steroidogenesis

What is Androgen Insensitivity Syndrome (AIS)

A condition where cells lack functional androgen receptors; 46,XY individuals develop female external genitalia despite high testosterone levels.

Phenotypically: Genetically male (XY) but phenotypically female with testes and no uterus.

What is environmental sex determination

Temperature during egg incubation.

ex. * Red-eared slider turtle

• American alligator

• Alligator snapping turtle

• some fish

In turtles:

• Low temperature: ↑ Sox9 expression → male development

• High temperature: ↓ Sox9 expression → female development

What is sex reversal

The ability of some animals to change sex during their lifetime based on social or environmental cues.

Ex. Clownfish.

• smaller fish are male.

• There is only one breeding pair per group (dominant male and female).

• If the female is removed, the male mate transforms into a female.

• The next largest male becomes the new dominant male.

Ensures continuous reproduction in small social groups even if the dominant female dies.