Sex determination

Question 1

When does sex determination begin?

Answer 1

At fertilization

Question 2

What determines the sex of the individual?

Answer 2

-By sperm (+/- Y) and the subsequent genetic control of sex differentiation

Question 3

Germ line formation

Answer 3

Occurs during the formation of mesoderm and endoderm , when a population of the epiblast cells are put aside for the germ line

Question 4

Primordial Germ Cell Migration

Answer 4

-Are displaced from the embryonic disk to the definitive yolk sac and part of the allantois
Then they proliferatie and migrate as a group from allantois base and yolk sac to the hindgut, then gonadal ridge

Question 5

What induces PGC migration?

Answer 5

Somatic cells around the PGCs secrete chemoattractants in which PGCs have receptors for

Question 6

What do somatic cells do to maintain PGC viability during migration?

Answer 6

Somatic cells produce survival factors

Question 7

What keep PGCs grouped together?

Answer 7

Membrane adhesion proteins like E-cadherins

Question 8

What promotes PGC interaction with extracellular environment?

Answer 8

Membrane receptors such as integrins

Question 9

What happens to PGCs outside the gonadal/genital ridge?

Answer 9

They will die

Question 10

Gonadal ridge

Answer 10

**considered a bipotential gonad due to its ability at this point to develop in two different pathways:
1. Ovary
2.Testes

Question 11

Where does gonadal ridge form?

Answer 11

Medial to the embryonic kidneys (mesonephros)

Question 12

What occurs to the Gonadal ridge when Primordial Germ cells arrive?

Answer 12

They stimulate cells around them to proliferate and cause ridge elongation

Question 13

Origin of gonadal ridge cells (somatic)

Answer 13

-local mesenchymal cells
-coelomic epithelium
-cells from mesonephric tubules

Question 14

What forms the primitive sex cords?

Answer 14

Degenerating mesonephric tubule cells which form compact strands of tissue called primitive sex cords which incorporate PGCs

Question 15

Changing of PGCs within the gonadal ridge

Answer 15

-occurs regardless of genetic makeup
-PGCs enter the ridge and undergo morphological and biological changes
-Caused by somatic cells in the ridge that secrete signals inducing the switch from PGC to more germ-like cells to proceed towards sperm or oocyte development

Question 16

What determines the phenotypic sex of an individual?

Answer 16

Governed by type of gonad that develops in the embryo- determined by the chromosome complement or genetic sex (Y chromosome)

Question 17

Gonads role in phenotypic sex

Answer 17

Gonads will produce sex-specific hormones leading to development of internal genitalia and secondary sex characteristics, and external genitalia

Question 18

Disorders of sex development

Answer 18

**occurs if regulation of network of transcription factors and cell signalling molecules fail

Includes:
-ambiguous or maldeveloped genitalia
-gonadal dysfunction
-infertility
-complete sex reversal in both male and females

Question 19

Sex Determining Region on Y chromosome

Answer 19

Y chromosome contains the SRY gene
-encodes for SRY protein (testes determining factor/TDF) and when it is produced by somatic cells fo primitive sex cords within primitive gonads, male reproductive system is stimulated to develop

Question 20

Genetic Sex Differentiation

Answer 20

determination of sex based on SRY gene and SRY protein

Question 21

SRY and Sox9

Answer 21

When SRY reaches threshold, will induce expression of Sox9.

Sox9 will result in sertoli cell differentiation

Question 22

Testes development

Answer 22

~5-15 mesonephric tubules or cell groups from the tubules penetrate into the primitive gonad

**paramesonephric duct serves no function here in male

Question 23

Development of the seminiferous cords

Answer 23

-Primitive sex cords proliferate into seminiferous or testis cords that are solid tubules containing germ cells

Question 24

Seminiferous cord components

Answer 24

Tubules contain peripheral layer of 15-20 coelomic derived cells that become Sertoli cells

Mesencymal cells and mesonephric cells between the cords develop into Leydig or interstitial cells

Question 25

What do sertoli cells surround in seminiferous cords?

Answer 25

Surround central core of pro-spermatogonia

Question 26

Sertoli cells purpose when stimulated by high Sox9

Answer 26

1.prevention of meiosis entry leading to germ cells and quiescent pro-spermatogonia
2. Secrete morphogens resulting in Leydig cells
3.Play a role in peritubular myoid cells of cord

Question 27

Seminiferous cords at puberty

Answer 27

Seminiferous cords become seminiferous tubules with a lumen and continuity between rete tubules and efferent ducts

Question 28

Mesonephic duct development at puberty

Answer 28

Develops into the epididymis and the ductus deferens

Question 29

Excurrent extragonadal duct system

Answer 29

Includes the efferent ducts, epididymis, and ductus deferens

Function to carry sperm through to the urethra

Question 30

Events leading to female sex phenotypic determination

Answer 30

-Determined by sex chromosomes (X does not have SRY!). Therefore cells express female promoting genes and inhibit male promoting genes

**lacking single genetic switch, but still needs key genes for development

Question 31

Foxl2 (Forkhead box L2)

Answer 31

-gene transcription factor and one of the earliest to be induced in developing female specific ovary

**mutation in goats= female to male sex reversal

Question 32

Foxl2 role in postnatal life

Answer 32

-Maintenance of ovary by suppressing genes involved in testis determination from embryonic to adult life

Question 33

Ovary development

Answer 33

1.No SRY protein, so some of degenerating sex cords and coelomic cells surround the primitive germ cells and differentiate into primitive follicular or pre-granulosa cells
2.Mesonephric duct intact early, but will start to regress while rete tubules degenerate. No direct duct outlet for gametes like in male
3.Paramesonephric duct develops further, with opening that will be infundibulum
*degree of fusion of paramesonephric ducts and urogenital sinus= different uterine types
4. Primitive follicular cells surrounding primitive germ cells do not penetrate, will stay on periphery and become cortex
5. Sex cords disappear completely= non germinal medulla

Question 34

What are primitive germ cells in developing ovary called?

Answer 34

Oogonia

Question 35

Growth Differentiation Factor 9

Answer 35

-produced by XX oocyte in developing follicle

-Function to induce granulosa cells to secrete morphogens to stimulate gene specific thecal cell programming

Question 36

Thecal cells

Answer 36

Will produce androgens (under LH control) which is converted into Estradiol within the granulosa cells

Question 37

Major differences between male and female differentiation pathways

Answer 37

1. Male: high Sox9 and Sertoli cells resulting in Leydig cells
2. Female: Sox9 off, High RSPO1,Wn4 and Granulosa cells resulting in thecal cells

Question 38

Origin of Granulosa and sertoli cells

Answer 38

Origin from coelomic somatic cells of gonadal ridge

Question 39

Origin of Leydig and Thecal cells

Answer 39

Origin from mesonephric and mesenchymal somatic cells of gonadal ridge

Question 40

Sex determination pathways active suppression

Answer 40

Male and female sex determination pathways actively suppress one another:
1.during gonad differentiation
2.After testes or ovaries have developed

Question 41

Testes and ovary conversion

Answer 41

Easily converted
-constant expression of specific genes is needed to suppress opposing pathway and prevent transdifferentiation

Question 42

What species has sex reversal been described?

Answer 42

-dogs, horses, pigs, goats

**higher frequency in pigs and goats

Question 43

Polled Intersex syndrome

Answer 43

-high frequency in goats
-due to depletion within chromosome that directly effects transcription of two genes:
1.one associated with hornlessness (Polled)- dominant allele
2. Ovarian development (Foxl2)