Reproduction L01 Sexual Differentiation

Front 1

What are the 3 major systems in forming internal and external genitalia?

Back 1

Wolffian (mesonephric) ducts, Müllerian (paramesonephric) ducs, and Urogenital sinus.

Front 2

Match the system (Wolffian, Müllerian, Urogenic) with the development of the follow: upper 4/5 of uterus

Back 2

Müllerian: upper 4/5 of vagina

Front 3

Match the system (Wolffian, Müllerian, Urogenic) with the development of the follow: lower 1/5 of the uterus

Back 3

Urogenital sinus: lower 1/5 of the vagina

Front 4

Match the system (Wolffian, Müllerian, Urogenic) with the development of the follow: male internal genitalia

Back 4

Wolffian: male internal genitalia

Front 5

Match the system (Wolffian, Müllerian, Urogenic) with the development of the follow: External genetalia

Back 5

Urogenital sinus: External genetalia (male & female)

Front 6

Match the system (Wolffian, Müllerian, Urogenic) with the development of the follow: Female internal genitalia

Back 6

Müllerian: Female internal genitalia

Front 7

Match the system (Wolffian, Müllerian, Urogenic) with the development of the follow: Urologic track (male and female)

Back 7

Wolffian: Urologic track (male and female)

Front 8

In which week to gonads appear?

Back 8

4-5 week

Front 9

What will happen if germ cells fail to migrate from the yolk sak to the genital ridge?

Back 9

If germ cells fail to migrate from the yolk sak to the genital ridge, GONADAL AGENESIS

Front 10

(1) Which chromosome has the genetic switch for testicular development AND where is it located… (2) what is the name of the factor that initates the genetic switch? (3) what is the timeline for genetic switching? (hint: 6-7 vs. 8-9)

Back 10

(1) Which chromosome has the genetic switch for testicular development? THE DISTAL P-ARM OF THE "Y" CHROMOSOME: "SRY"… (2) what is the name of the factor that initates the genetic switch? TESTIS DETERMINING FACTOR (TDF)… (3) what is the timeline for genetic switching? IF TDF (SRY) by 6-7 WEEKS --> TESTIS.... IF NO TDF (SRY) by 8-9 WEEKS --> OVARIES

Front 11

What is in the SRY of chromosome Y?

Back 11

SRY: transcriptional factor, HMG box =binds DNA promotor region of genes important in expression of male genital ridge at appropriate time

Front 12

What arises in males in the presence of SRY at 6-7 weeks?

Back 12

With SRY: Sertoli cells + Leydig cells form

Front 13

What do Sertoli cells produce during sexual differentiation that is important to development?

Back 13

Sertoli cells: produce MIF (Müllerian inhibiting factor --> no upper 4/5th of vagina, no internal female genetalia

Front 14

What do Leydig cells produce during sexual differentiation that is important to development?

Back 14

What do Leydig cells produce during sexual differentiation that is important to development? Testosterone: which maintains Wolffian ducts and virilizes external genetalia

Front 15

If there is no SRY, what 2 things will happen?

Back 15

No SRY (1) --> no MIF --> Müllarian ducts maintained… (2) No Testosterone --> Wolffian duct regress --> no external virilization

Front 16

What does Testosterone do in sexual differentiation?

Back 16

Testosterone: maintains Wolffian ducts (external male genetalia) and virilizes external genetalia

Front 17

Which pathway(male or female is favored by the following: SOX9, DAX-I/DSS, SF-1, WT-1

Back 17

MALE: SOX9, SF-1, WT-1… FEMALE: DAX-I/DSS,

Front 18

What can a defect in SOX9 cause?

Back 18

SOX9 defect: 46 XY female and campomelic dysplasia (bowing of long bones)

Front 19

What can a SF-1 defect cause

Back 19

SF-1 defect: adrenal failure, and sexual differentiation problem

Front 20

What can a WT-1 defect cause? (hint: Triad)

Back 20

What can a WT-1 defect cause? Wilm tumor + kidney failure, + frasier synd, 46 xy sex reversal and Denis-Drash syndrome

(all kidney and sex differentiation related)

Front 21

What can a DAX-1/DSS defect cause?

Back 21

What can a DAX-1/DSS defect cause? Adrenal hypoplasia and reversed XY

Front 22

What of SOX9, WT1, and SF-1, which directly stimulates the testis?

Back 22

What of SOX9, WT1, and SF-1, which directly stimulates the testis? All of them

Front 23

What stimulates SOX9?

Back 23

SRY, SF-1, WT1 and SOX9 itself stimuates SOX9

Front 24

What produces testosterone and MIF?

Back 24

The testis produces T and MIF

Front 25

What inhibits SOX9?

Back 25

DAX-1 inhibits SOX9

Front 26

What inhibits DAX-1?

Back 26

SRY

Front 27

What stimulates DAX-1 and thereby inhibits SOX-9 and leads to default to ovaries?

Back 27

WNT4 stimulate DAX-1 --> suppression of SOX9 and leads to default ovaries

Front 28

Which enzyme do Leydig cells have, and what does this enzyme convert?

Back 28

Which enzyme do Leydig cells have, and what does this enzymeconvert? 5 ∂ reductase... T -->DHT

Front 29

What do sertoli cells produce?

Back 29

Sertoli cells --> form testicular cords --> MIF

Front 30

Give the time line of beginning of ovary fomation, ooctyes, to pirmordial follicles.

Back 30

8-9 weeks: ovary fomation… 11-12 weeks: discernable ooctyes… 14th week: pirmordial follicles.

Front 31

In Males: what do Leydig cells produce and what are the effects of this product on the internal genitalia development?

Back 31

Leydig --> T --> (1) Wolffian ducts convert to vasa deferentia, semianl vessicles and epididymis. (2) and separate into kidneys and ureters.

Front 32

In Males: what do sertoli cells produce and what are the effects of this product on the internal genitalia development?

Back 32

Sertoli cells --> MIF --> Müllerian regession

Front 33

What remnant is left when MIF causes the Müllerian ducts to regress?

Back 33

What remnant is left when MIF causes the Müllerian ducts to regress? PROSTATIC UTRICAL

Front 34

In females, what does a lack of T cause?

Back 34

In females, a lack of T causes the regress of the Wolffian ducts

Front 35

In females, what does a lack of MIF cause?

Back 35

No MIF: 2 Müllerian ducts contact in midline, fuse and canalize--> form uterus, tubes and upper 4/5 of the vagina

Front 36

MATCH THESE FEMALE UROGENIC SINUS STRUCTURES: clitoris, labial minor, lower 1/5 of vagina, labial majora, urethra… WITH THESE MALE UROGENIC STRUCTURES: urethra, glans penis, penile shaft, scrotum, labioscrotal fusion.

Back 36

FEMALE=MALE: urethra=urethra…Clitoris=Glans penis… Labial minora=Penile shaft… Labial majora=Scrotum… Lower 1/5 of Vagina=Labioscrotal fusion

Front 37

What is the "Conversion Hypothesis" with respect to the brain.

Back 37

The "Conversion Hypothesis" ascerts that the brain is intrinsically female… HOWEVER, E --> hypothalamus & amydala --> defeminization... HOWEVER, in Females binding proteins prevent E from entering the brain… AND in Males: T--> aromatase --> E (enters brain)... thus T --> masculinization.

In females, binding proteins prevent E from entering the brain

Front 38

What is androgen insensitivity?

Back 38

Androgen Insensitivity: Inactive Androgen-® (not reactive to T or DHT)

Front 39

Do people with androgen insenstivity have normal SRY, MIF and T?

Back 39

Yes, 46 xy --> SRY… and Gonads are testes --> MIF & T

Front 40

Given that people with adrogen insensitivity produce SRY, MIF and T, what ducts remain?

Back 40

With SRY (TDH) --> Gonads (testis) --> MIF and T... (a) Leydig cells --> T --> No T-® --> no maintenance of Wolfian Ducts --> regression of Wolffian ducts ... (b) Sertoli cells --> MIF (is independent of T-®) --> regression of Müllerian ducts

Front 41

Given that people with adrogen insensitivity can still produce SRY and MIF --> thus they don't make Müllerian ducts, what are the ramification of no Müllerian ducts?

Back 41

With SRY (TDH) --> Gonads (testis) --> MIF: (b) Sertoli cells --> MIF (is independent of T-®) --> regression of Müllerian ducts --> no uterus, no tubes, no upper 4/5 of vagina...

Front 42

Given that people with adrogen insensitivity can still produce SRY but they don't make T --> they can't maintain Wolffian ducts, what are the ramification of no Wolffian ducts?

Back 42

With SRY (TDH) --> Gonads (testis) --> MIF and T... (a) Leydig cells --> T --> No T-® --> no maintenance of Wolfian Ducts --> regression of Wolffian ducts --> no virilization of external genitalia…

Front 43

Given that people with adrogen insensitivity can still produce SRY but they don't make T --> they can't maintain Wolffian ducts, what are the ramification of no Wolffian ducts... ALSO, given that people with adrogen insensitivity can still produce SRY and MIF --> thus they don't make Müllerian ducts, what are the ramification of no Müllerian ducts... AND given that androgen insensitive people still have a functional UROGENITAL SINUS

Back 43

With SRY (TDH) --> Gonads (testis) --> MIF and T... (a) Leydig cells --> T --> No T-® --> no maintenance of Wolfian Ducts --> regression of Wolffian ducts --> no virilization of external genitalia… (b) Sertoli cells --> MIF (is independent of T-®) --> regression of Müllerian ducts (+ prostatic utricle) --> no uterus, no tubes, no upper 4/5 of vagina... (NOTE: default structures formed by the UROGENITAL SINUS are female --> THUS, external genitalia (no virilization), lower 1/5 of vagina

Front 44

What are the characteristic of an Androgen Insensitive person?

Back 44

Regression of Müllerian (MIF present) and Regression of Wolffian ducts (No T-® sensitivity no maintenance), No virilization (noWD) of default external genitalia (+ US), No upper 4/5 of vagina (no MD), no uterus (no MD), no tubes, with lower 1/5 of vagina-small vagina (+ US) ... Also Scan pubic hair and large breast (No T-®)...

Front 45

Why is it that Androgen Insensitivity and 5∂ Reductase deficiency have different characteristics?

Back 45

Both are 46 xy: With 5∂ Reductase there is T it's just not convereted to the more potent DHT… Both Androgen Insensitivity and 5∂ Reductase deficiency start off very similar (SRY --> MIF + T), Wolffian ducts develop - yet without DHT, their development is insufficient to produce early virilization of external genitalia… HOWEVER, in puberty T overrides androgen receptor to start virilization ==> PENIS AT 13

Front 46

In Müllerian Agenesis what is the genetic sex? What is the central problem?

Back 46

In Müllerian Agenesis, the genetic sex is 46 XX… The central problem is Müllerian ducts regress.

Front 47

Since in Müllerian Agenesis there is a failure of the In Müllerian ducts to develop and there is no T, what are the sexual characteristics?

Back 47

In Müllerian Agenesis (with Müllerian duct regress): Default mechanism, i.e., US is in effect, but no MD, no WD… thus no virilization of external genetalia (no WD), no uterus or tube (no MD), no upper 4/5th of vagina (no MD)… however with US: lower 1/5 of vagina… with normal pubic hair and normal breasts

Front 48

In Turner syndrome what is the genetic sex? what is the effect on the Müllerian ducts and the Wolffian ducts?

Back 48

Turner's Syndrome: 45X… (2) No Wolffian ducts… but Müllerian ducts develop.

Front 49

Since Turner's Syndrome has 45,X, and Müllerian duct develop, but Wolffian ducts regress, what are the sexual characteristic?

Back 49

Turner's Syndrome: US: lower 1/5th of vagina, with default female external genetial… MD: upper 4/5th of vagina… NO WD: NO virilization of external genetalia… with scant pubic hair and small breast and normal vagina, normla uterus, and streak ovaries.

Front 50

What are the two sex reversed syndromes? And what causes the problem?

Back 50

46 XY Female: deletions on SRY: no MIF no T (similar to 5∂ reductase deficiency)… 46 XX Male: trasnslocation of SRY to X: MIF and T (masculinization of external genetalia, no upper 4/5th of Vagina)