Development Of The Genital System Flashcards

1
Q

Name the week:

Indifferent embryo

Sexual differentiation begins

Female and male genitalia can be recognized

Phenotypic differentiation complete

A

Weeks 1-6

Week 7

Week 12

Week 20

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2
Q

What is the indifferent gonad?

Where do they end up after gastrulation and body folding?

Where and when do they migrate after that?

A

Primordial germ cells specified within epiblasts

Yolk sac wall

Migrate up dorsal mesentery to enter genital ridge; week 5

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3
Q

When is the gonad indifferent?

What are the male and female somatic support cells?

A

Week 6

Male: Sertoli cells

Female: follicle cells

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4
Q

Both genital ducts form in the ____ of the urogenital ridge.

What are the two ducts and what do they become?

Which duct was a part of early kidney development?

A

Intermediate mesoderm

Mesonephric (Wolffian) ducts: epididymis, vas deferens, seminal vesicle, ejaculatory duct

Paramesonephric (Mullerian) ducts: oviduct, uterus, upper vagina

Mesonephric (Wolffian) ducts

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5
Q

Sexual dimorphism is dependent on the ____ chromosome and ____.

____ gene is on the sex-determining region of the Y chromosome

What does this gene determine?

Without this gene, continued development is ____ with ____ positively driving this development.

A

Y; autosomes

SRY

The gonad type and duct and genitalia development

Female; genes

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6
Q

What gene determines the formation of testis?

What chromosome is it on?

When is it active?

What cells express this gene?

A

SRY gene (also called TDF/testis determining factor)

Y chromosome

41-52 days

Somatic support cells (pre-Sertoli)

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7
Q

What is the job of the SRY gene?

____ surround primordial germ cells to organize/become seminiferous tubules.

Subset of intertubular cells differentiated into _____; recruited by ______.

A

Up-regulates testis-specific genes; drives formation of Sertoli cells from somatic cells

Sertoli cells

Fetal leydig cells; Sertoli cells

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8
Q

This gene is driven by SRY

Function of this gene

What remnants are left from the paramesonephric duct in males?

A

Sox9

Drives the production of Anti-Mullerian Hormone (AMH) from the Sertoli cells -> inhibits development of Mullerian (paramesonephric) ducts between weeks 8-10

Appendix testis, prostatic utricle

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9
Q

Leydig-derived testosterone drives the development of what?

This will form what in males?

When does the paramesonephric duct degenerate in males?

A

Mesonephric ducts

Epididymis, efferent ductules, vas deferens, seminal vesicles

Week 9

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10
Q

Sertoli cells generate ____ which cause regression of _____.

Sertoli cells also generate ____ which causes spermatogonia to become spermatozoa during ____.

A

AMH; paramesonephric ducts

Androgen binding factor; spermatogenesis

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11
Q

When do fetal leydig cells regress?

What do fetal leydig cells produce and what is the fx?

A

Fetal/early post natal life

Testosterone: causes mesonephric duct to become the ductus deferens, epididymis, seminal vesicle during weeks 8-12; driven by HCG of placenta

5 alpha reductase: causes testosterone to become dihydrotestosterone (DHT)

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12
Q

DHT drives the formation of what?

Adult leydig cells secrete ____.

What do they do?

A

Genital tubercle -> penis
Genital swellings -> scrotum
Urethral epithelium -> prostate

Androgens

Initiation of spermatogenesis, masculinization of brain, male sexual behavior

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13
Q

Development of the external genitalia begins with ____ external genitalia.

Rupture of cloacal membrane opens the phallic portion of urogenital sinus to exterior, forming an endodermally-lined plate called what?

What are remnants of the cloacal membrane at the ventral end of urogenital plate?

What is the ectodermally-covered mesodermal swelling at ventral and cranial end of phallic portion of urogenital plate?

A

Indifferent

Urogenital plate (endodermally lined)

Glans plate

Genital tubercle (mesoderm covered by ectoderm)

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14
Q

What is the urogenital plate?

When does it form?

___ drives lengthening and growth of genital tubercle and fusion of labioscrotal swellings to form sacrum.

____ continues to elongate creating a future urethra inside a tube of ____.

When is the urethral groove closed?

A

Remnant of phallic segment after cloacal membrane rupture

Early 7th week

DHT

Urogenital plate with ventral glans plate; urogental folds

Week 14

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15
Q

Gonads start around ____ and descend.

What shortens and becomes the anchoring ligament of the testis to the scrotum?

It is connected to the ____.

A

T10

Gubernaculum

Labia/scrotal swelling

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16
Q

The most common birth defect after cryptorchidism; urethral folds on either side of UG plate don’t fuse; urethra opens in inferior side of penis

Other birth defect associated with exstrophy of bladder; problem with anterior wall closure of the bladder

A

Hypospadias

Epispadias

17
Q

Females don’t have ____, allowing ____ to initially suppress sox9 expression.

____ continually suppresses Sox9; maintaining female gonad (suppress Sertoli cell and Leydig cell differentiation).

Somatic cells differentiate into ____; primordial germ cells differentiate into _____.

Oogonia proliferate and differentiate into ____.

____ surrounds oocytes in inhibit further meiosis; oocytes stuck in meiosis I until ____.

A

SRY; Wnt4

FOXL2

Follicle cells; oogonia

Oocytes

Follicle cells; puberty

18
Q

In females, no Sertoli cells therefore no ____; paramesonephric ducts are retained.

No leydig cells so _____ is lost.

Persistence of Müllerian (paramesonephric) ducts creates ____.

A

AMH

Mesonephric duct

Uterine tubes, uterus, vagina (upper portion)

19
Q

When does the uterus form?

How does it formed?

What drives this formation?

____ are the unfused superior portion of the paramesonephric ducts.

What is a remnant of the mesonephric duct in females?

A

Weeks 9-10

Inferior paramesonephric ducts near the urogenital sinus fuse and form the uterus

Estrogen and progesterone from placenta

Uterine tubes

Gartner’s duct

20
Q

What are uterus anomalies?

How do these form?

A
Double uterus; double vagina 
Double uterus
Bicornate uterus
Septated uterus
Unicornate uterus
Cervical atresia

Mainly formed because of lack of fusion of the paramesonephric ducts

21
Q

Paramesonephric ducts fuse on the _____; this stimulates formation of the ____.

What is the upper vagina derived from?

Lower vagina?

The vagina is eventually ___.

What causes vaginal agenesis?

A

Urogential sinus; sinovaginal wall

Mesoderm; from paramesonephric duct system

Endoderm; from sinovaginal wall

Recanalize

Due to failure of normal vaginal plate development or failed canalizations

22
Q

Phallic segment of the urogenital sinus forms what in the female?

Urethral portion of urogenital sinus becomes what?

A

Urogenital plate, glans plate, genital tubercle

Membranous urethra

23
Q

No testosterone leads to no dihydrotestosterone and therefore no _____ and ______ in females.

A

No lengthening of genital tubercle and no fusion of urogenital folds or labioscrotal swellings

24
Q

How does the broad ligament form?

Upon completion of uterus and oviduct formation, the remaining tissue thins and forms a _____ which supports ____.

A

Midline fusion of paramesonephric ducts; brings lower urogenital ridge within the pelvic cavity and is covered with peritoneum

Double fold of peritoneum (broad ligament and mesovarian); uterus and ovary

25
Superior gubernaculum forms what? Inferior gubernaculum forms what?
Round L of ovary (connects to uterus) Round L of uterus (connects uterus to labia majora)
26
What is pseudohermaphroditism/disorders of sex development (DSD)? Genotypic sex is masked by ____.
Congenital conditions which development of chromosomal, gonadal, and anatomic sex is atypical Phenotypic appearance resembling opposite sex or having reproductive organs of opposite sex
27
What is 46, XY DSD (disorders of sex development)? What disorders does this cause?
Genotype 46, XY Has testis but phenotype is female Inadequate testosterone synthesis due to 17 beta-hydroxysteroid dehydrogenase Androgen insensitivity syndrome 5 alpha-reductive deficiency (no DHT) Mutations in AMH or AMH receptor
28
What is androgen insensitivity syndrome? What happens at puberty? What do these pts have a higher risk of developing?
Loss of functional androgen receptors (X-linked recessive); have testis but no spermatogenesis; testosterone levels may be high (neg feedback) At puberty, testosterone is metabolized to estradiol initiating female secondary characteristics; pts have amenorrhea Produce AMH so paramesonephric system is suppressed; no uterus or uterine tubes, short vagina Testis found in inguinal of labial regions Increased risk for tumor formation in gonads
29
Where are the seminal vesicles, vas deferens, epididymus, and efferent ductules derived from? Where is the prostate gland derived from and when? Where is the bulbourethral gland derived form?
Buds from the mesonephric duct (intermediated mesoderm of the urogential ridge) Buds form the endoderm of the UG sinus in the region of the pelvic urethra; week 10 Endodermal buds
30
Derivatives of embryonic male and female reproductive structures: 1. Indifferent gonad 2. Primordial germ cell 3. Somatic support cell 4. Stromal cells 5. Gubernaculum 6. Mesonephric tubules 7. Mesonephric duct
1. Testis; ovary 2. Spermatogonia; oocytes 3. Sertoli cells; follicle cells 4. Leydig cells; thecal cells 5. Gubernaculum testis; round ligament of ovary and uterus 6. Efferent ducts of testis, paradidymis; epoophoron, paroophoron 7. Appendix of epididymus, vas deferens, seminal vesicle, ejaculatory duct; duct of epoophoron, gartner’s duct
31
Derivatives of embryonic male and female reproductive structures: 8. Paramesonephric duct 9. Urogenital sinus 10. Genital tubercle 11. Urogenital folds, urogential plate, and glans plate 12. Labioscrotal folds
8. Appendix of testis, prostatic utricle; uterine tubes, uterus, vagina 9. Prostatic and membranous urethra, prostatic gland, bulbourethral glands; membranous urethra, urethral/paraurethral glands, greater vestibular glands 10. Glands penis, corpus cavernosum of penis, corpus spongiosum of penis; glands clitoris, corpus cavernosum of clitoris, bulbospongiosum of vestibule 11. Penile urethral/ventral penis; Labia minora 12. Scrotum; Labia majora
32
What is 5 alpha-reductase deficiency?
46, XY genotype Autosomal recessive At birth: have male internal genitalia (testosterone) but ambiguous external genitalia; Normal testis and duct system; can make AMH and testosterone Underdeveloped male external genitalia; may have external female phenotype *At puberty: testosterone levels surge and cause masculinization and male external genitalia
33
What are female DSDs? What is the most common cause? What mutations cause this?
46, XX genotype Have ovaries; Fetus produces excess androgens; masculinization of female external genitalia; labia may fuse to look like scrotum Congenital adrenal hyperplasia: most common cause of female sexual ambiguity Mutations in genes involving adrenocortical steroid biosynthesis (21 hydroxylase deficiency)
34
What are ovotesticular disorders? (True intersexuality) What causes this?
Have both testicular and ovarian tissue Ambiguous external genitalia or mainly female; usually have uterus Caused by translocation of piece of Y onto X (Barr body causes mosaicism); subset of cells may have a mutation in Y; anomaly in sex determination and differentiation of primordial germ cells