Endo 16: Development Of Reproductive System

Front 1

A reproductive system contains what three groups of organs?

Back 1

- Gonads
- Reproductive ducts
- External genitalia

Front 2

Where are the gametes produced?

Back 2

Paired gonads aka sex glands

Front 3

What is the primary origin of the sex steroid hormones?

Back 3

Paired gonads aka sex glands

Front 4

Once produced, where do gametes pass?

Back 4

Through series of Reproductive Ducts

Front 5

What happens in the Reproductive Ducts?

Back 5

- Gametes pass through here
- In the female, the ducts are a site for development of the embryo
- Also provides for the events of parturition

Front 6

What organ is involved in gamete delivery and reception during coitus?

Back 6

External Genitalia

Front 7

What are the two components of establishing "sex"?

Back 7

- Sex determination = genetic sex
- Sex differentiation = phenotypic sex

Front 8

What is established during sex determination? How?

Back 8

Genetic Sex
- Established by the complement of sex chromosomes in the genome

Front 9

When is sex determination (genetic sex) established?

Back 9

At fertilization when the male and female gamete form a zygote having either XY or XX sex chromosome content

Front 10

What is established during sex differentiation? How?

Back 10

Phenotypic Sex
- Influenced by genetic and epigenetic factors

Front 11

When is sex differentiation (phenotypic sex) established?

Back 11

Occurs during and after the embryonic period

Front 12

What influences the sex differentiation (phenotypic sex) in the male direction?

Back 12

Presence of androgens during formation of sex organs

Front 13

What is the monohormone theory of sexual differentiation?

Back 13

- Presence of androgens during formation of sex organs influences sex differentiation in a male direction
- If no androgens are present, the fetus continues to develop female sex organs

Front 14

What happens to a male if castration occurs before sexual differentiation?

Back 14

Formation of female ducts and external genitalia (female phenotype with male genotype)

Front 15

What happens to a male if castration occurs before sexual differentiation but androgens are added?

Back 15

Both male and female duct systems are present but with male external genitalia

Front 16

What happen to a male if he is given anti-androgen?

Back 16

Neither male or female duct system is present but with female external genitalia

Front 17

Why would a castrated male given androgens develop both male and female duct systems and male external genitalia?

Back 17

- Androgen alone is not able to promote regression of the female ducts
- Müllerian Inhibiting Substance (MIS) or Factor (MIF) or Anti-Müllerian Hormone acts on the precursors of the oviducts, uterus, and part of the vagina
- Binding of MIS to its receptors causes apoptosis of the paramesonephric ducts

Front 18

What is the term for the precursors of the oviducts, uterus, and part of the vagina?

Back 18

Paramesonephric or Müllerian Ducts

Front 19

What is the action of Müllerian Inhibiting Substance (MIS) or Factor (MIF) or Anti-Müllerian Hormone?

Back 19

Binding of MIS to its receptors on the paramesonephric aka Müllerian ducts causes apoptosis of the future oviducts, uterus, and part of the vagina

Front 20

How is sexual differentiation in the brain controlled?

Back 20

- Occurs in the brain centers controlling the pituitary
- Pulsatile release of gonadotrophin releasing hormone from hypothalamus controls male or female patterns of gonadotropin release from pituitary gland
- In males, differentiation of brain is caused by a surge of T at about 6 months after birth

Front 21

When are reproductive organs morphologically indistinct with respect to sex differentiation?

Back 21

During the Indifferent Stage (weeks 4-6), this stage is longer for the genitalia

Front 22

What precursor tissue forms the gonads? How does this occur?

Back 22

- Ventromedial portion of the nephrogenic ridge as a proliferation of the overlying coelomic epithelium and the ridge mesenchyme
- Nephrogenic ridge now becomes known as the Urogenital (UG) Ridge

Front 23

What happens to the ventromedial portion of the nephrogenic ridge to form the gonads?

Back 23

- Proliferation of the overlying coelomic epithelium and the ridge mesenchyme
- Nephrogenic ridge now becomes known as the Urogenital (UG) ridge

Front 24

What are the original gonad cell types?

Back 24

- Germinal cells
- Supporting cells
- Interstitial or steroid producing cells

Front 25

What do the primordial germ cells form from?

Back 25

Extragonadal origin probably from cells in the epiblast (exact precursor has not been identified)

Front 26

When and where are primordial germ cells first seen?

Back 26

Yolk sac wall during week 3 as large cells with a unique staining pattern

Front 27

What happens to the primordial germ cells first seen in the yolk sac wall during week 3?

Back 27

During week 4-5, they migrate to the gonad within the dorsal mesentery of the hindgut

Front 28

What happens to the primordial germ cells after they migrate to the gonad during week 4-5?

Back 28

- During week 5-6, the germ cells proliferate as they migrate and continue to divide after they have reached the gonad
- Once they become associated with or surrounded by epithelial supporting cells derived from a proliferation of the coelomic epithelium

Front 29

What are the gonadal supporting cells in males and females? Function?

Back 29

- Sertoli cells (M)
- Granulosa cells (F)
- They play a role in organizing the gonad

Front 30

What are the gonadal interstitial cells in males and females? Function?

Back 30

- Leydig cells (M)
- Theca cells (F)
- Synthesize and secrete steroid hormones (primarily androgens)

Front 31

What kind of cells are Sertoli cells (M) and Granulosa cells (F)? Origin?

Back 31

Supporting cells
- Originate from cord-like proliferations of the coelomic epithelium overlying the gonad primordium

Front 32

What happens to the germ cells if the supporting cells do not invest?

Back 32

Germ cells atrophy

Front 33

What kind of cells are Leydig cells (M) and Theca cells (F)? Origin?

Back 33

Interstitial cells
- Originate from mesonephric mesenchyme cells

Front 34

What do the gonads attach to?

Back 34

Mesenchymal tissues:
- Cranially (superiorly) - Suspensory Ligament
- Caudally (inferiorly) - Gubernaculum (Genito-Inguinal Ligament)
- Dorsally (posteriorly) - dorsal mesentery

Front 35

What is the function of the Suspensory Ligament?

Back 35

- Mesenchyme that attaches to the gonad cranially (superiorly)
- Within it, develops the vascular supply to the gonad

Front 36

Where is the vascular supply to the gonad?

Back 36

Within the Suspensory Ligament (mesenchyme that attaches to the cranial aspect of the gonad)

Front 37

What is the function of the Gubernaculum?

Back 37

Condensation of mesenchyme that attaches the primitive gonad to the ventral body wall

Front 38

What are the two genital duct systems that develop during the indifferent stage? When do they form?

Back 38

- Mesonephric Ducts aka Wolffian Ducts - week 4
- Paramesonephric Ducts aka Müllerian Ducts - week 6

Front 39

Where do the Mesonephric aka Wolffian Ducts form? When do they form?

Back 39

Within the nephrogenic ridges as part of the mesonephros

Front 40

What signals development of the Paramesonephric aka Müllerian Ducts?

Back 40

Signals from the Mesonephric aka Wolffian ducts

Front 41

What do the Paramesonephric aka Müllerian Ducts begin as?

Back 41

Each duct begins as an invagination of the coelomic epithelium covering the lateral aspect of the UG ridge

Front 42

What happens to the Paramesonephric aka Müllerian Ducts initially?

Back 42

- Initially the invagination forms a solid cord of cells that grows inferiorly toward the cloaca but lateral to the mesonephric duct
- As the ducts grow medially toward the cloaca, the ducts lie ventral and superior tot he mesonephric ducts

Front 43

What happens after the Paramesonephric aka Müllerian Ducts grow medially toward the cloaca?

Back 43

The inferior 1/3 of the paramesonephric ducts fuse together in the midline forming the Uterovaginal Primordium

Front 44

What forms the Uterovaginal Primordium?

Back 44

The fusion of the inferior 1/3 of the paramesonephric ducts in the midline

Front 45

What happens after the Uterovaginal Primordium is formed from the inferior 1/3 of the paramesonephric ducts fusing?

Back 45

- The Uterovaginal Primordium contacts the posterior aspect of the cloaca causing a swelling of the back wall in the area of the forming UG sinus (pelvic part)
- This forms the Sinus (Müllerian) Tubercle

Front 46

What do the paramesonephric ducts open into?

Back 46

UG sinus on either side of the Sinus (Müllerian) Tubercle, a lumen forms in the ducts as they develop

Front 47

What are the primorida of the external genitalia?

Back 47

- Genital tubercle
- Urethral folds
- Labioscrotal swellings

Front 48

What is the appearance of the Genital Tubercle? Origin?

Back 48

- Midline swelling
- Derived from mesenchyme adjacent to phallic part of UG sinus

Front 49

What is the appearance of the Urethral Folds?

Back 49

- Paired swellings surrounding the cloacal membrane
- Initially they are called the cloacal folds

Front 50

What is the appearance of the Labiosacral Swellings?

Back 50

- Paired swellings lateral to the urethral folds
- Little change in their appearance until the fetal period

Front 51

What does a sexually determined but sexually undifferentiated embryo develop during weeks 4-6?

Back 51

- Pair of undifferentiated gonads
- Two sets of ducts - mesonephric and paramesonephric
- A set of elevations and folds around the cloacal membrane

Front 52

What gene is responsible for testicular determination?

Back 52

SRY Gene = Sex-determining Region Y
- Found ont he short arm of the Y chromosome
- Encodes a DNA binding protein called Testicular Determining Factor

Front 53

When is the SRY gene expressed? Function?

Back 53

During week 6 in males
- Expressed by the supporting cells of the genital ridge
- Causes the supporting cells to differentiate into Sertoli cells
- Begin to express Sox9

Front 54

What do Sertoli cells begin to express after differentiating due to the action of SRY?

Back 54

Sertoli Cells express Sox9

Front 55

What ist he origin of the Sertoli Cells?

Back 55

Coelomic epithelial cords that extend into the mesenchyme of the forming testis

Front 56

What do the Sertoli Cells do once they have differentiated?

Back 56

- Surround the primordial germ cells inhibiting their progression to meiosis
- Sertoli cells and primordial germ cells organize into Testicular Cords

Front 57

What are Testicular Cords made of? What do they form?

Back 57

- Made of Sertoli Cells and Primordial Germ Cells
- At or before puberty the cords develop a lumen and are known as the Seminiferous Tubules

Front 58

What tissue forms the Seminiferous Tubules? When dot hey form?

Back 58

Testicular Cords = Sertoli Cells and Primordial Germ Cells (without a lumen)
- Once it forms a lumen it is known as the Seminiferous Tubules
- Forms at or before puberty

Front 59

What do the Sertoli cells organize into in the area adjacent to he mesonephros?

Back 59

Rete Testis

Front 60

What do Sertoli cells begin to secrete as they differentiate?

Back 60

MIF: Müllerian Inhibiting Factor

Front 61

What do signals from Sertoli cells recruit at 8 weeks?

Back 61

Recruit adjacent mesenchyme cells which differentiate into Interstitial / Leydig cells

Front 62

What is the action of Leydig cells? How is it regulated?

Back 62

- Secrete Testosterone, converting a 21C precursor to a 19C steroid hormone
- This is initially regulated by chorionic gonadotrophin secreted by the trophoblast

Front 63

What happens to the testis as it continues to grow?

Back 63

- Separates from the mesonephros
- Covering coelomic epithelium becomes separated from underlying testicular cords by a condensation of mesenchyme cells that forms a thick CT layer called the Tunica Albuginea

Front 64

What causes the testis to descend into the scrotum?

Back 64

Shortening of the gubernaculum

Front 65

How often are the testes undescended at birth? What is this called?

Back 65

2-3% of newborns
- Cryptorchidism

Front 66

When does organization of the ovary occur in comparison to when it occurs for a testis?

Back 66

Ovary organization occurs later than for testis

Front 67

What causes ovaries to develop?

Back 67

Females have no Y chromosome, therefore they do not express the SRY gene

Front 68

What happens to the Primordial Germ Cells developing in an ovary?

Back 68

Primordial germ cells enter the meiotic prophase and are committed to oogenesis

Front 69

What do the oocytes produce to stimulate the supporting cells?

Back 69

Oocytes produce FIGα which stimulates the supporting cells to differentiate into Follicle Cells that surround the oocytes

Front 70

What do the Oocyte and the surrounding Follicle Cells form?

Back 70

Primordial Follicle

Front 71

What are the components of a Primordial Follicle?

Back 71

- Oocyte
- Follicle Cells

Front 72

What signal arrests oocyte meiosis in meiotic prophase? Source?

Back 72

Meiosis Inhibiting Factor is produced by Follicle Cells

Front 73

What happens to germ cells that do not have a surrounding of Follicle Cells?

Back 73

Oocytes will atrophy

Front 74

What prevents mesenchyme cells in females from becoming Leydig cells?

Back 74

Wnt4 signaling

Front 75

What is required for normal ovarian development?

Back 75

Two X chromosomes

Front 76

What forms beneath the coelomic epithelium covering the ovary?

Back 76

Thin Tunica Albuginea

Front 77

Does the ovary change position?

Back 77

Ovaries descend into the pelvis (week 12)

Front 78

What duct system forms in males? What structures are derived from these ducts?

Back 78

Mesonephric Ducts, forms:
- Duct of Epididymis
- Ductus Deferens
- Ejaculatory Ducts
- Efferent Ductules

Front 79

What structure connects the rete testis with the duct of the epididymis? What is it derived from?

Back 79

Efferent Ductules - derived from the mesonephric duct

Front 80

Where is T converted to DHT? How?

Back 80

- Converted in the Mesonephric Ducts by 5α-Reductase
- Also in the prostate

Front 81

What does the prostate gland develop from?

Back 81

- Epithelial buds of endoderm from the prostatic urethra (most of the gland tissue is formed from these buds)
- However, some glands surrounding the ejaculatory ducts (central zone) may originate from mesoderm rather than endoderm

Front 82

What do the Seminal Vesicles form from?

Back 82

- Outgrowths of the mesonephric duct just before it enters the forming prostate gland
- Mesenchyme surrounding the glandular buds of the prostate and seminal vesicles form the CT and smooth muscle components in the wall of these glands

Front 83

What happens to the Paramesonephric Ducts in males? How?

Back 83

These are suppressed by MIS (Müllerian Inhibiting Substance) which causes atrophy of these ducts

Front 84

What is derived from the Paramesonephric Ducts in males?

Back 84

Cranial part of the prostatic utricle

Front 85

What duct systems develop / regress in females?

Back 85

- Mesonephric Ducts atrophy d/t absence of T
- Paramesonephric Ducts develop d/t lack of MIF (Müllerian Inhibiting Factor)

Front 86

What develops from the Paramesonephric Ducts in females?

Back 86

- Unfused cranial 2/3 become the OVIDUCTS
- Inferior 1/3 fuses with opposite side to become the UTEROVAGINAL PRIMORDIUM (most of which forms the uterus - body and cervix)

Front 87

What does the vagina originate from?

Back 87

- Paramesonephric ducts
- Urogenital sinus

Front 88

What does the Uterovaginal Primordium form?

Back 88

- Most becomes the uterus (body and cervix)
- Contributes to vagina

Front 89

What does the Uterovaginal Primordium connect with inferiorly to finish the vagina?

Back 89

- Inferior tip of the Uterovaginal Primordium contacts the posterior wall of the UG sinus (pelvic part)
- Stimulates formation of a swelling or thickening, the Mullerian or Sinus Tubercle

Front 90

What extends from the Mullerian or Sinus Tubercle (swelling / thickening formed from Uterovaginal Primordium and UG sinus contact)? Effect?

Back 90

Paired, solid outgrowths, Sinovaginal Bulbs, extend dorsally from the Sinus Tubercle pushing the Paramesonephric Ducts superiorly

Front 91

What happens to the Sinovaginal Bulbs (paired, solid outgrowths of the Sinus Tubercle)?

Back 91

Sinovaginal Bulbs fuse to form a Vaginal Plate that becomes canalized

Front 92

What is the epithelial lining of the vagina derived from?

Back 92

- Upper part of the vagina is derived from the inferior part of the uterovaginal primordium
- Lower part is formed from the sinovaginal bulbs

Front 93

What forms the remaining tissue of the vaginal wall?

Back 93

Surrounding mesenchyme

Front 94

What separates the vagina from the UG sinus?

Back 94

A membrane - the Hymen

Front 95

How common is a complete septum across the vagina? What is this called?

Back 95

3% of the population has a hymen that forms a complete septum across the vagina, known as the Imperforate Hymen

Front 96

When is an Imperforat Hymen discovered?

Back 96

When the child begins to menstruate during puberty

Front 97

What are some anomalies of the uterus and vagina?

Back 97

- Absence of uterus and vagina
- Duplication of uterus and vagina
- Vaginal Atresia (10% isolated) or with Uterine Aplasia/Atresia (90%)
- Complete or incomplete septa may subdivide the uterine lumen

Front 98

What could cause duplication of the uterus or vagina?

Back 98

Incomplete merging of the paramesonephric ducts (which merged to form the unpaired uterovaginal primoridum)

Front 99

What are the parts of the UG sinus?

Back 99

- Vesicle (superior)
- Pelvic (intermediate)
- Phallic (inferior)

Front 100

What does the Pelvic Part of the UG sinus form in males and females?

Back 100

Males:
- Epithelial lining of the distal part of the prostatic urethra and membranous urethra

Females:
- Epithelial lining of the inferior parts of the vagina

Front 101

What does the Phallic Part of the UG sinus form in males and females?

Back 101

Males:
- Epithelial lining of the penile urethra

Females:
- Epithelial lining of the vestibule

Front 102

What does the penis form from?

Back 102

- Genital Tubercle elongates during the indifferent stages to become the Phallus
- Urethral Plate (extension of endoderm in the roof of the phallic part of the UG sinus)

Front 103

What happens as the phallus elongates in the male?

Back 103

- Pulls the urethral folds forward causing them to fuse on the ventral surface
- Pulls the UG sinus anteriorly
- Deepens the urethral groove on inferior side of the phallus

Front 104

Where do the urethral folds fuse?

Back 104

Urethral folds fuse as the phallus elongates along the ventral surface of the phallus

Front 105

Where does the penile urethra form?

Back 105

Within the urethral groove (mechanism unclear) and urethral plate contributes to formation too

Front 106

The development of the male external genitalia and its maintenance is supported by what hormone(s)?

Back 106

Androgen (Dihydrotestosterone)

Front 107

How does the scrotum form?

Back 107

- Under androgen influence, the perineal area of the male embryo elongates
- Labiosacral swellings fuse ventrally forming the scrotum
- Inferior or caudal end of the gubernaculum is attached to the labioscrotal swellings
- Testis enters the scrotum via the inguinal canal prior to birth

Front 108

What is the gubernaculum attached to?

Back 108

Labioscrotal swellings (that forms the scrotum)

Front 109

How do the testis enter the scrotum?

Back 109

Via the inguinal canal prior to birth

Front 110

What are the penile anomalies? Which is more common?

Back 110

- Hypospadias: urethra opens ventrally
- Epispadias: urethra opens dorsally, 5x more common

Front 111

What is the term for a urethra opening on the ventral surface of the penis? Why does this occur? Other features?

Back 111

Hypospadias
- Occurs because of incomplete fusion of the urethral folds
- There may also be a ventral bend in the penis

Front 112

What is the term for a urethra opening on the dorsal surface of the penis? Why does this occur? Other features?

Back 112

Epispadias
- Five times more common than epispadias
- Usually associated with bladder exstrophy and rarely occurs as an isolated condition

Front 113

Does the perineal area elongate in males or females? Why?

Back 113

- Males: elongates in presence of androgen
- Females: does not elongate d/t no androgen

Front 114

What happens to the phallus in the female?

Back 114

Bends inferiorly to form the Clitoris

Front 115

What forms the epithelial lining of the vestibule of the vagina?

Back 115

Phallic portion of the UG sinus

Front 116

How does the fate of the urethral folds differ in males and females?

Back 116

- Males: fuse during elongation of the phallus on the ventral surface
- Females: remain unfused and form the Labia Minora

Front 117

What forms the Labia Minora? Labia Majora?

Back 117

- Labia Minora: unfused urethral folds
- Labia Majora: unfused labioscrotal swellings

Front 118

How does the fate of the labioscrotal swellings differ in males and females?

Back 118

- Males: fuses ventrally to form the scrotum
- Females: remains unfused to form the Labia Majora except for minimal fusion at the anterior end which forms the Mons Pubis

Front 119

What does the Mons Pubis form from?

Back 119

Anterior fusion of the Labioscrotal Swelling

Front 120

What stimulates development of the female external genitalia?

Back 120

Estrogens

Front 121

When does sex determination occur?

Back 121

Fertilization

Front 122

When does sex differentiation occur?

Back 122

During embryonic and fetal periods

Front 123

What happens during the indifferent stage?

Back 123

Undifferentiated gonads, ducts, and external genitalia form initially

Front 124

What directs undifferentiated gonads to form testes?

Back 124

SRY gene

Front 125

What ducts form in males? How?

Back 125

- Mesonephric ducts is supported by androgens from testes and forms the male duct system (except urethra)
- MIS inhibits development of the Pramesonephric ducts

Front 126

What directs undifferentiated gonads to form ovaries?

Back 126

Absence of SRY gene expression

Front 127

What ducts form in females? How?

Back 127

- Absence of androgens allows Mesonephric Duct to atrophy and allows external genitalia primordia to develop in the female direction (supported by estrogen)
- Absence of MIS allows Paramesonephric Ducts to develop and form the female duct system (except caudal vagina)