6. Development of Genitalia Flashcards
1
Q
What are the 3 big players that help to make our gonads?
A
1. Intermediate mesoderm, which makes our nephrogenic cord and urogenital ridge mesenchyme
2. Coelomic epithelium (aka somatic support cells/mesothelium), from somatic layer of the lateral plate mesoderm.
3. Allantois/yolk sac endoderm, which is where primordial germ cells reside.
2
Q
What is the coelmic epithelium?
A
Coelomic epithelium (aka somatic support cells/mesothelium) is the outer somatic mesoderm that lines the urogenital (gonadal) ridge. It will create our primary sex cords, which will become the CTX and medulla of the gonads (testes and ovaries).
3
Q
Primordial germ cells are found in the allantois/yolk sac mesoderm. Where are they derived from?
A
Epiblast
4
Q
What gives rise to the male internal genitalia?
A
Mesonephric duct (Wolfian Duct)
5
Q
What gives rise to the female internal genetelia?
A
Paramesonephric duct (mueller duct)
6
Q
Primordial germ cells come from the epiblast. However, they need support from other cells as well.
In M, what are these cells and where are they derived from?
A
- Sertoli cells, from C.E
- Leydig (interstitial) cells, from I.M
7
Q
Primordial germ cells come from the epiblast. However, they need support from other cells as well.
In F, what are these cells and where are they derived from?
A
- 1. Follicle cells (from C.E).
- 2. Thecal cells (from I.M)
8
Q
What is gametogenesis?
A
Formation of the primary germ cells (egg and sperm)
9
Q
Describe the process of gametogenesis.
A
- Primary germ cells arise from the epiblast @ week 2.
- Week 3, they migrate through the primitive streak -> reside in the yolk sac and allantois to avoid signals that could cause them to form different cells.
- Week 5, they then migrate to the dorsal mesentery.
- Week 6, they move to the primary sex cords (urogenital ridge).
10
Q
Moms action during pregnancy can affect her bby and her grandkids. HOW?
A
Mom’s actions impact germ cells of the fetus.
11
Q
What is oogenesis?
A
Development of eggs
12
Q
What processes do oognia occur to increase in number?
A
mitosis
13
Q
How many eggs will we have at 5th month prenatal, birth and puberty?
How many will then be released?
A
- 5th month prenatal -> 6. MIL
- Birth-> 1 MILL (they then undergo atresia)
- Puberty -> 40k
- However, we will only release about 400.
14
Q
Meiosis I occurs during _______.
Meiosis II occurs during _______.
A
- Meiosis I occurs during ovulation.
- Meiosis II occurs during fertilization.
15
Q
How come increasing age of the mothers is assx with increase number of genetic abnormalities in eggs?
A
The 400 eggs released are in a constant state of suspension. Thus, they sit around longer.
16
Q
What are the two events that determine sex?
A
- Central (main) event -> production of testes (genotype)
- Secondary event -> production of humoral factors by gonads (hormones that determine phenotype)
17
Q
What gene is responsible for genetype/phenotype of M/F?
A
- SRY gene (sex determining region Y human gene) codes for TDF (testis-determining factor), a DNA binding protein.
18
Q
What happens to XY mice that lack SRY gene?
A
Female and sterile
19
Q
What happens to transgenic mice with SRY gene?
A
They are males. Will have normal sertoli cells, leydig cells, normal sexual behavior, no hermaphroditism, but they are sterile.
20
Q
SRY is a switch that control genes in M/F/both
A
BOTH MALES AN FEMALES.
21
Q
What occurs when SRY gene is present?
A
- I.M will give rise to Leydig cells -> make testosterone -> cause the mesonephric duct to persist -> undergo remodeling and make internal male genetalia -> via DHT -> will make male external genitalia.
- C.E will give rise to Sertoli cells -> make AMH (anti-Mullerian hormone) -> cause paramesopnephric duct to degenerate -> also contributing to formation of male external genitalia
22
Q
What occurs when SRY gene is absent?
A
- I.M will give rise to thecal cells -> do NOT make testosterone -> cause the mesonephric duct to degenerate (will not make M internal genetalia and bc no DHT, no male external)
- C.E will give rise to follical cells -> make NO AMH (anti-Mullerian hormone) -> cause paramesopnephric duct to persist -> make Female internal genetalia -> make female external genetalia
23
Q
A
24
Q
Ovotesticular DSD used to be called what?
A
true hermaphrodite.
25
**46, XX DSD** used to be called what?
**Female pseudohermaphrodite**
26
**46 XY DSD** used to be called what?
**Male pseudohermaphrodite**
27
What is **ovotesticular DSD**?
Ovotesticular DSD is _true gonadal intersex_: gonads have components of both and it is poorly understood.
* Thus, they both testicular and ovarian tissue and an ovotestis.
* Phenotype: M or F
* External genitalia: ambiguous
28
People with **ovotesticular DSD** are
* \_\_\_\_% 46XX
* \_\_\_\_% 46XX/XY mosaicism
* \_\_\_% 46XY
* **70% 46XX**
* **20% 46XX/XY mosaicism**
* **10% 46XY**
29
What is **46 XX DSD**?
A **genotypically female**, but is _exposed to excessive androgens._
* Thus, female has _ovaries_, but _external genitalia is masculinized_
* clitoral hypertrophy
* fusion of labia majora
* persistant urogenital sinus
30
**46 XX DSD** is caused by exposure of a female fetus to too much androgens. What conditions can cause excessive androgens?
**Congenital adrenal hyperplasia (CAH)** d/t deficient 21-hydroxylase. This causes a reduction in cortisol and too many androgens.
31
What causes **46XY DSD**?
**1. Not enough production of testosterone and/or AMH.**
**2. Androgen insensitivity syndrome**
32
What do we see in ppl with **46XY DSD**??
* 1. Development of testicles is underdeveloped -\> normal
* 2. May have persistant paramesonephric ducts
* 3. External genitalia are F or ambigous.
33
**Androgen insensitivity syndrome** is a subtype of \_\_\_\_\_\_.
Genetypically, they are \_\_\_\_\_.
AIS is a **46XY DSD.** Genotypically, they are **M** but they are not exposed to androgens.
* Thus, they have _normal appearing female external genitalia._
34
**What features do we see in AIS?**
What do we see at puberty?
* 1. Blind end vagina
* 2. Absent or underdeveloped [uterus and uterine tubes].
* 3. At puberty, normal breast development and female characteristics, but no period.
35
**_SRY present_**
**1. What happens when _no AMH_?**
Internal/external genitalia?
Paranephric duct persists.
Thus, will have:
* Both _M/F internal genitelia_
* _M external genitelia._
* 46XY DSD.
36
**_SRY present_**
**What happens when _5-alpha-reductase deficiency?_**
Internal/external genitalia?
**5-alpha-reductase converts testosterone -\> DHT.**
* Male internal genitalia
* Ambigous (or female) external genitalia until puberty.
37
* Weeks \_\_\_\_: Indifferent embryo
* Week \_\_\_: Sexual differentiation begins
* Week \_\_\_: Female and male genitalia can be recognized
* Week \_\_\_: Phenotypic differentiation complete
* **Weeks 1-6 I**ndifferent embryo •
* **Week 7** Sexual differentiation begins •
* **Week 12** Female and male genitalia can be recognized •
* **Week 20** Phenotypic differentiation complete
38
**Describe _M and F gonad development_ (indifferent stage)**
* 1. Begins at week 5 in the lumbar region. At this stage, gonads are indifferent.
* 2. Wk 5: urogenital (gonadal) ridge forms on medial side of mesonephros
* 3. Wk 6: 1st wave of cells come from C.E -\> developing gonads to make the _primary sex cords_ in the medulla. This persists in males, but degenerates in females.
* 4. By the 6th week, primordial germ cells migrate along dorsal mesentary -\> gonadal ridges.
* 5. 2nd waves of cells come from C.E to make our secondary sex cords (cortical cords) in CTX.
39
Differentiation into testes
1. Primary sex cords persist (from C.E) and become
* seminiferous cords
* sertoli cells.
2. Connective tissue (From I.M) becomes
* leydig cells
* tunica albuginea.
40
Where are sertoli cells derived from and what do they make?
Surface epithelium and make AMH.
41
Differentiation into ovaries
1. **Secondary sex cords (cortical cords)** persist and become
1. primordial ovarian follicles, made via mitosis.
2. granulosa cells
2. **Thecal cells** are made from I.M
42
During indifferent stage, what ducts are present?
We have 2 ducts:
* 1. **Mesopnephric (Wolffian) ducts,** which persist in males.
* 2. **Paranephric (Mullerian) ducts,** which persists in females.
43
Mesonephric (Wolffian) ducts persist in males and degenerate in females.
## Footnote
**Reminants in females are called what?**
**1. Epoophoron**
**2. Paroophoron**
**3. Gartners cyst (located on lateral wall of vagina)**
44
How do we then differentiate into the **Male Ductal System**?
1. **Sertoli cells** -\> secrete AMH -\> cause paramesonephirc duct to degenerate.
2. **Leydig cells** -\> secrete testosterone -\> cause mesonephric duct retention
45
What does the **mesonephric duct** give rise to?
* **1. Epididymis (& appendix of epididymis)**
* **2. Ductus deferens**
* **3. Seminal vesicle**
* **4. Ejaculatory duct**
46
The **mesonephric tubules**, on the mesonephric duct, will give rise to what?
**1. Efferent ductules**
**2. Rete testis**
47
Reminants of **mullerian (paramesophric ducts)** in males are
**1. Utriculus prostaticus**
**2. Appendix testis**
48
How do we then differentiate into the **Female Ductal System**?
1. **Paramesonephric ducts** persist on lateral coelomic bay
* Cranial part forms the _uterine tubes._
* Caudal region of the paramesonephric ducts fuse and make the _uterovaginal primordium_ (_uterus_ and _vagina_)
2. PM ducts then go to urogenital sinus and make the _sinus tubercle._
49
Describe the **differentiation into the uterus and vagina.**
* 1. **Uterovaginal primordium (fused paramesonephric ducts)** contact the **urogenital sinus**, forming the **sinus tubercle** •
* 2. The sinus tubercle forms the **sinovaginal bulbs (**endodermal outgrowths that extend from the urogenital sinus -\> uterovaginal plate)
* 3. The sinovaginal bulbs fuse to form the **vaginal plate** (a tube full of cells)
* 4. The vaginal plate will indergo apoptosis and recanilization to form the _lumen of the vagina_
50
The **vaginal canal** is derived from what 2 sources?
1. Superior 1/3 comes from paramesonephric duct (intermediate mesoderm)
2. Lower 2/3 comes from hindgut endoderm.
51
***UTERUS ANOMALIES: what happened?***
1. Didelphys (double uterus) and double vagina
2. Uterus arcuatus (indendation of uterus)
3. Uterus bicornis (1 vagina and 2 uteruses)
1. Didelphys (double uterus) and double vagina -\> paramesonephric ducts did not fuse. (??? listen)
2. Uterus arcuatus- paramesophric duct did not fuse completely.
3. Uterus bicornis- paramesophric duct did not fuse completely.
52
**UTERUS ANOMOLIES: What happened?**
1. Uterus bicornic unicolis with 1 rudementary horn
2. Cervical atresia
3. Vaginal atresia.
* 1. Uterus bicornic unicolis with 1 rudementary horn- paramesonephric duct atrophied
* 2. Cervical atresia- paramesonephric duct atrophied in the caudal region
* 3. Vaginal atresia.- no sinovaginal bulbs formed/or atrophy of vaginal plate.
53
11. Describe the contribution of the urogenital sinus to the male reproductive system.
**Urogenital sinus** is **hindgut endoderm.** It forms:
1. **Prostate**
* Made from pelvic part of the urogenital sinus (endoderm)
* smooth muscle and CT of prostate come from splanchnic mesoderm
2. **Bulbourethral glands**
* made from phallic part of urogenital sinus (endoderm)
* smooth muscle and CT come from splanchnic mesoderm
54
Male external genitalia is under influence of \_\_\_\_\_
DHT
55
Female external genitalia is under influence of \_\_\_\_\_
Estrogen
56
**Male external genitalia** is under influence of DHT, which will do what?
1. Drive lengthening and growth of **genital tubercle**, which makes the _glans penis_
2. Fusion of **urethral (urogenital folds)** to make the _spongy urethra_ and _penile raphe_
3. Fusion of l**abioscrotal swellings** to make _scrotum_
57
Female external genitalia is under influence of estrogen, which will do what?
1. **Genital tubercle** -\> glans clitoris
2. **Urethral (urogental) folds** d_o not fuse_ and instead make frenulum of labia minor and majora
3. **Labioscrotal swellings** to do not fuse and instead make labium majus and mons pubis.
58
How do we allow the spongy urethra to reach the external surface?
UG folds fused to make spongy urethra. However, it did not make it to the external surface. To do so, we form the _**navicular fossa** via proliferation of surface ectoderm._
Fusion of the two will allow spongy urethra to reach external surface.
59
What are **_hypospadias_**?
Most common birth defect where there is an openining of the ventral surface of the penis.
60
**How can we get:**
1. _glandular hypospadia_
2. Penile hypospadia
3. Penoscotal hypospadia
1. glandular hypospadia-\> incomplete closure of urogental (urethra) folds or urogenital fossa
2. Penile hypospadia -incomplete closure of urogental folds on shaft of penis.
3. Penoscotal hypospadia- lack of fusion between labioscotal swellings.
61
What is an **epispadia**?
* Opening of the dorsal side of the penis d/t misplacement of genital tubercles to cloachal membrane.
* It is estrophy of the bladder
62
What are the ligaments of the ovaries?
tissue is derived. from?
1. **Suspensory ligament** (mesoderm)
2. **Ovarian ligament**, which is made from cranial part of gubernaculum (mesoderm)
63
What. are the L of the uterus?
1. **Round ligament of uterus, from caudal part of gubernaculum**
2. **Broad ligament**
64
How is the **broad ligament** formed?
1. Paramesonephric ducts fuse along peritoneal fold.
2. This separates the pelvic cavity to make the _rectouterine pouch_ and _vesicouterine pouch_
