Development of the Genital System

Question 1

Overall timeline of sexual differentiation
Wks 1-6
Wk 7
Wk 12
Wk 20

Answer 1

1-6: indifferent embryo

7: sex diff begins
12: F and M genitalia can be recognized
20: phenotypic diff complete

Question 2

Describe the path of the primordial germ cell in the indifferent gonad

Answer 2

• germ cells specified within epiblasts
• after gastrulation and body folding, they end up in the yolk sac wall
• they migrate up the dorsal mesentery to enter the genital ridge

Question 3

What somatic support cells, found in the 6 wk indifferent gonad, differentiate ultimately into what (M and F)?

Answer 3

M: Sertoli
F: follicle

Question 4

What type of ‘derm’ do both ducts (parameso- and meso- nephric) form from?

Answer 4

intermediate mesoderm of the urogenital ridge

Question 5

What are the ultimate structures of the mesonephric duct?

Answer 5

epididymis
vas deferens
seminal cesicle
ejaculatory duct

Question 6

What are the ultimate structures of the paramesonephric duct?

Answer 6

oviduct
uterus
upper vagina

Question 7

What is the gene of the sex-determining region of the Y chromosome?

Answer 7

SRY gene

Question 8

Sexual dimorphism depends on what 2 things? (one specific, one general)

Answer 8

Y chromosome

but also some autosomes

Question 9

What is the importance of the SRY gene?

Answer 9

determines gonad type, which determines duct and genitalia development

Question 10

What two factors determine F development? (general)

Answer 10

absence of SRY

also genes that positively drive F development

Question 11

SRY Gene:

• which chromosome?
• active during what days?
• expressed in what cells?
• AKA?
• function?

Answer 11

Y Chrm
41052 days
somatic support cells (pre-Sertoli)
TDF: testis determining factor
upregulates testis-specific genes

Question 12

How do seminiferous tubules organize?

Answer 12

Sertolis surround primordial germ cells

Question 13

What do Leydig cells differentiate from?

Answer 13

subset of intertubular cells

Question 14

What do Sertoli cells contribute to male diff?

Answer 14

Anti-Mullerian Hormone: regression of paramesonephric ducts

androgen binding factor: spermatogonia –> spermatozoa

Question 15

What are the contributions to male diff made by fetal Leydig cells?

Answer 15

-testosterone; weeks 8-12; driven by hCG of placenta
mesonephric duct –> ductus deferense, epididymis, seminal vesicle

5 alpha-reductase (T –> DHT):
genital tubercle –> penis
genital swellings –> scrotum
urethral epithelium –> prostate

Question 16

What are the contributions that adult Leydig cells make to male diff?

Answer 16

drives androgens –>
initiation of spermatogenesis
“masculinization” of brain
male sex behavior

Question 17

What does the seminal vesicle bud from?

Answer 17

mesonephric duct (intermediate meso of UG ridge)

Question 18

What does the prostate gland bud from?

Answer 18

endoderm of UG sinus in region of pelvic urethra

week 10

Question 19

Where do the bulbourethral glands come from?

Answer 19

endodermal buds

Question 20

How does the UG plate form?

Answer 20

remnants of the cloacal membrane opens phallic portion of UG sinus to exterior
plate lined w/ endoderm

Question 21

How does the glans plate form?

Answer 21

from remnants of the cloacal mem at the ventral end of the UG plate and the adjacent genital tubercle

Question 22

What is the genital tubercle?

Answer 22

extodermal-covered mesodermal swelling at ventral and cranial end of the phallic portion of the UG plate

Question 23

Epispadias are associated with what other condition?

Answer 23

Exstrophy of the bladder

Question 24

What factor is SUPPRESSED to allow female gonadal diff?

Answer 24

SOX-9

Question 25

How is Sox-9 initially suppressed?

Answer 25

No SRY, allowing Wnt-4 to suppress Sox-9 expression

Question 26

After Wnt-4, what suppressed SOX-9?

Answer 26

FOXL2 continualy suppresses SOX-9, maintaining female gonad

Question 27

in F, primordial germ cells differentiate into what? | and those proliferate, then differentiate into what?

Answer 27

oogonia; oocytes

Question 28

Oocytes surround what?

Answer 28

follicle cells

Question 29

Since F do not have Sertoli's, what hormone is ABSENT, and what structure is RETAINED?

Answer 29

Anti-Mullerian Hormone | paramesonephric ducts aka Mullerian ducts

Question 30

What do Mullerian (parameso) ducts differentiate into? (3)

Answer 30

Fallopian tubes Uterus Upper vagina?

Question 31

When and how does the uterus form?

Answer 31

When: wk 9-10 how: fusion of inferior Mullerian (parameso) ducts

Question 32

What are oviducts made from?

Answer 32

unfused superior portion of the Mullerian (parameso) ducts

Question 33

Term for double uterus?

Answer 33

didelphys

Question 34

What is the upper vagina derived from?

Answer 34

mesoderm

Question 35

What is the lower vagina derived from?

Answer 35

endoderm

Question 36

What two factors can lead to vaginal agenesis?

Answer 36

either failure of normal vaginal plate development OR failed canalization

Question 37

What 3 structures make up the phallic segment of the urogenital sinus?

Answer 37

UG plate glans plate genital tubercle

Question 38

What embryo structure --> roung lig of ovary? Connects what to what?

Answer 38

superior gubernaculum | ovary to uterus

Question 39

What embryo structure --> roung lig of uterus? Connects what to what?

Answer 39

inferior gubernaculum | uterus to labia majora

Question 40

Rudimentary stromal cells --> M and F?

Answer 40

M: Leydig F: thecal cells

Question 41

Rudimentary gubernaculum --> M and F?

Answer 41

M: gubernaculum testis F: Round ligs X 2

Question 42

Rudimentary parameso ducts --> M and F?

Answer 42

M: mostly gone, but leaves behind appendix of testis and prostatic utricle F: fallopian tubes, uterus, vagina

Question 43

Rudimentary UG sinus --> M and F?

Answer 43

M: prostatic + membranous urethra; prostate gland; bulbourethral glands F: membranous urethra, urethral/paraurethral glands, greater vestibular glands

Question 44

Rudimentary genital tubercle --> M and F?

Answer 44

M: glans penis, corpora cavernosa, corpus spongiosum F: glans clitoris, corpora cavernosa, bulbospongiosum of vestibule

Question 45

Rudimentary UG folds + UG and glands plates --> M and F?

Answer 45

M: penile urethra/ventral part of penis F: labia minora

Question 46

Rudimentary labioscrotal folds --> M and F?

Answer 46

M: scrotum F: labia majora

Question 47

What is pseudohermaphroditism (aka disorders of sex development, DSD)?

Answer 47

genotypic sex is masked by pheno appearance resembling opposite sex, or having repro organs of the opposite sex

Question 48

What is the phenotype of a 46 XY DSD? | What are 4 causes of this?

Answer 48

female 1. inadequate T synthesis 2. androgen insensitivity syndrome 3. 5 alpha reductase deficiency 4. mutations in AMH or AMH receptor

Question 49

Describe Androgen Insensitivity Syndrome

Answer 49

46 XY DSD, so female phenotype common cause: loss of functional androgen receptors X linked recessive have testis, but no spermatogenesis, w/ poss high T levels testes found in inguinal or labial regions @ puberty, T --> estradiol --> female sex traits + amenorrhea AMH+, so parameso system is suppressed no uterus or tubes vagina is short + blind ended risk of tumors and malignancies

Question 50

Describe 5 alpha reductase deficiency

Answer 50

``` 46 XY genotype autosomal recessive normal testis and duct system underdeveloped male external genitalia depending on level of deficiency, CAN have F external pheno ```

Question 51

Female DSDs = 46 XX - what gonad do they have - what happens in fetal life to lead to symptoms?

Answer 51

ovaries fetus produces excess androgens --> masculinization of female external genitalia *fusion of labia gives appearance of scrotum

Question 52

What is the most common cause of female sexual ambiguity?

Answer 52

Congenital adrenal hyperplasia | specifically 21 hydroxylase

Question 53

Describe Ovotesticular Disorders (True Intersexuality)

Answer 53

- have both testicular and ovarian tissue - ambig genitalia or predom female - uterus + **true sex = what they can best adapt to in society

Question 54

3 causes of ovotesticular disorders?

Answer 54

- translocation of Y onto X (Barr body causes mosaicism) - subset of cells w/ mut in Y - anomaly in sex det and diff of primordial germ cells