6 Embryology 5

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Renal System Development
10th week
~12 weeks
Dental Human Embryology Course (DENT 5315/OBIO-8024)
Brad Martinsen, Ph.D. (marti198@umn.edu)
Lecture 5:
Topic
Assigned Reading
Renal Development
pages 265-276
Genital Development
pages 276-288
The PowerPoint notes pages give a complete review of the reading
assignments (Larson’s Human Embryology, 3rd ed.) and what I will say in
lecture. You can also refer to the Larson’s Human Embryology Website
(http://cna.uc.edu/embryology/) and click on contents for Animations,
Updates, Self-tests, and Glossaries of Terms for each Chapter.
*Use reading assignments to clarify anything said in lecture or in the
notes.
Not all detail in the reading assignments will be on the exams.
1
Development of Three Nephric Systems
Cervical Nephrotomes & Mesonephroi
Upper thoracic
region to the
third lumbar
region
I. Development of Three Nephric Systems.
Note: The intermediate mesoderm (Fig 10-1) gives rise to the nephric
structures of the embryo, to portions of the gonads, and to the male genital duct
system. Three sets of nephric structures (cervical nephrotomes,
mesonephroi, and metanephroi, the definitive kidneys) develop in
craniocaudal succession from the intermediate mesoderm.
A. Cervical nephrotomes.
1. Early 4th week five to seven paired cervical segments of intermediate
mesoderm give rise to a nephric vesicle/nephrotome (small, hollow ball of
epithelium) (Fig 10-2A).
2. Also referred to as the pronephros (Greek for first kidney) because they
resemble the functional embryonic pronephroi of some lower vertebrates.
3. The cervical nephrotomes are transient and nonfunctional. They disappear
by day 24 or 25.
2
Development of Three Nephric Systems
Cervical Nephrotomes & Mesonephroi
Renal Corpuscle:
Glomerulus &
Bowman’s capsule
Mesonephric
excretory unit:
Renal corpuscle &
Nephric tubule
6-10weeks-func
>10-regress.
Mesonephric
ducts in females
regress and in
males they persist
to form parts of
male genital duct
system.
26 Days~22 days
Mesonephroi.
*Early in the 4th week the nephric (mesonephric) tubules develop within a
pair of mesonephroi/mesonephric ridges (elongated swellings of
intermediate mesoderm located on either side of the vertebral column) from the
upper thoracic region to the third lumbar level (Fig 10-2B-D). Also early in
the 4th week the mesonephric ducts (intermediate mesoderm origin) first
appear in the form of a pair of solid longitudinal rods (dorsolateral to the
developing mesonephric tubules) (Fig 10-2A & Fig 10-3). These rods grow
caudally into the lower lumbar region guided by an adhesion gradient between
the ectoderm and endoderm.
*By day 26, the rods diverge from the intermediate mesoderm and fuse with
the ventrolateral walls of the cloaca (Fig 10-2 & Fig 10-4). The region of
fusion eventually becomes the posterior wall of the future bladder. During
the fusion process the rods also begin to cavitate at their distal ends, forming a
lumen. Cavitation progresses cranially forming the mesonephric ducts. At
the end of 5th week the cranial regions of the mesonephroi undergo
regression, leaving about 20 pairs of tubules occupying the first three lumbar
levels.
3
Development of Three Nephric Systems
Cervical Nephrotomes & Mesonephroi
Renal Corpuscle:
Glomerulus &
Bowman’s capsule
Mesonephric
excretory unit:
Renal corpuscle &
Nephric tubule
6-10weeks-func
>10-regress.
Mesonephric
ducts in females
regress and in
males they persist
to form parts of
male genital duct
system.
26 Days~22 days
Mesonephroi.
*The mesonephric tubules differentiate into excretory units that resemble an
abbreviated version of the adult nephron (Fig 10-2D). The medial end of the
tubule forms the Bowman’s capsule (a cup-shaped sac) which raps around the
glomerulus (a knot of capillaries produced on branches of arteries sprouting
from the dorsal aorta), forming the renal corpuscle. Each renal corpuscle
and nephric tubule is called a mesonephric excretory unit. The lateral tip
of each mesonephric tubule fuses with the mesonephric duct, opening a
passage from the excretory units to the cloaca. During the 6th to 10th weeks
the mesonephric excretory units are functional and produce small amounts of
urine.
*After 10 weeks the mesonephric excretory units cease to function and then
regress. The mesenephric ducts regress in the female, but in the male the
mesonephric ducts plus a few modified mesonephric tubules persist and
form parts of the male genital duct system (we will talk about in more detail in
the next lecture).
4
Development of Three Nephric Systems.
Mesonephroi & Metanephroi
Regress to
the 1st three
lumbar levels
Sacral
Region
Mesonephric
duct forming
Reciprocal
induction
~22 days
Metanephroi or the definitive kidneys.
At the 4th week (day 28) the distal portion of the mesonephric ducts sprout ureteric buds
(eventually differentiates into the ureters and the collecting duct system of the kidneys)
which induce the metanephroi to form in the intermediate mesoderm of the sacral region
(Fig 10-4A). At Day 32 each ureteric bud penetrates the metanephric blastema (a portion of
the sacral intermediate mesoderm which appears around the same time) and begins to bifurcate
(Fig 10-4B). The metanephros become lobulated in appearance as each ampulla (growing tip
of each bifurcated branch) acquires a caplike aggregate of metanephric blastema tissue. The
metanephric blastema eventually differentiate into the nephrons (the definitive urine-forming
units of the kidneys).
During the middle of 6th week the developing metanephros consists of two lobes separated
by a sulcus (Fig 10-4C). By the end of the 16th week the metanephros consists of 14 to 16
lobes (Fig 10-4D) and the sulci between the lobes begin to fill in.
Note: The ureteric bud and metanephric blastema exert reciprocal inductive effects
(classic model of induction). Several hours of direct contact with a ureteric bud ampulla are
required to induce nephron differentiation in blastema tissue and the reciprocal inductive
signals from the metanephric blastema regulate the orderly bifurcation of the tips of the
ureteric buds (discussed in more detail below). If the ureteric bud is abnormal or missing,
the kidney does not develop.
5
Sequence of bifurcations.
11 additional
generations of
bifurcations-->
1-3 mil branches.
~22 days
32nd Week
8 months
Collecting duct system (entirely the product of the ureteric bud) of the
Metanephroi.
Note: The collecting duct system is produced by sequential bifurcation of
the ureteric bud. Urine produced by the nephrons flows through the
collecting tubules, minor calyces, major calyces, the renal pelvis, and finally,
the ureter. This path is called the collecting duct system.
Sequence of bifurcations (Fig 10-5 & Fig 10-6A):
During the middle of the 4th week when the ureteric bud first contacts the
metanephric blastema, its tip expands to form an initial ampulla that will give
rise to the renal pelvis. At the 6th week the ureteric bud bifurcates four times,
yielding 16 branches which coalesce to form two to four major calyces
extending from the renal pelvis. During the 7th week the next four
generations of branches also coalesce to form the minor calyces.
By 32 weeks 11 additional generations of bifurcation have formed 1 to 3
million branches. These will become the future collecting tubules (collecting
ducts) of the kidney (Fig 10-6A).
6
Nephron Development
Contains neural crest derived neurons. They play a role in
nephron induction. The neurons regulate blood flow and
secretory function.
9th week
~22 days
Nephron development (Fig 10-6B-F):
Each nephron originates as a vesicle within the blastemic cap (surrounding the
ampulla of a collecting duct) (Fig 10-6B). The vesicle elongates into a tubule.
7
Nephron Development
10th week
10weeks+-->func: gl. filtrate to urine,
but main func to produce amniotic fl.
Nephron development (Fig 10-6B-F):
*A capillary glomerulus forms near one end of the tubule. The tubule epithelium near the
differentiating glomerulus thins and then invaginates to form a Bowman’s capsule (surrounds
the glomerulus). Just as in the mesonephros, the renal corpuscle consists of a Bowman’s
capsule and the glomerulus.
*As the renal corpuscle is developing, the lengthening nephric tubule differentiates into the
proximal convoluted tubule, the descending and ascending limbs of the loop of Henle, and
the distal convoluted tubule. The definitive nephron with its renal corpuscle is called a
metanephric excretory unit. By the 10th week the tips of the distal convoluted tubules
connect to the collecting ducts. The metanephroi become functional. Blood plasma from
the glomerular capillaries is filtered by the renal corpuscle to produce a dilute glomerular
filtrate. The filtrate is concentrated and converted to urine by the convoluted tubules and the
loop of Henle. The urine then passes down the collecting system into the ureters and then the
bladder.
Note: The main function of the fetal kidneys is not to clear waste (mainly handled by the
placenta), but instead it supplements the production of amniotic fluid. Thus fetuses with
bilateral renal agenesis do not make enough amniotic fluid (oligohydramnios), confining the
fetus to an abnormally small amniotic space.
8
Definitive Kidney Architecture
Minor calyx
Major calyx
Pelvis
Contains the nephrons.
5th-15th weeks Renal Pyramid (inner medulla)
Contains the loops of Henle
and collecting ducts .
Definitive kidney architecture (Fig 10-7):
*During the 5th to 15th weeks the definitive kidney architecture is created. The kidney is
divided into an inner medulla (contains the collecting ducts and the loops of Henle) and an
outer cortex (contains the nephrons). Each minor calyx drains a tree of collecting ducts
within the renal pyramid that converge to form the renal papilla.
*The renal pyramids of the kidney are separated by renal column/columns of Bertin (cortical
tissue that contains nephrons). Thus the cortical tissue covers the outside of the kidney, as
well as projecting towards the pelvis. The nephrons arise from the cortical regions of the
primary lobes of the metanephric blastema.
Note: Neural crest cells contribute to the function of the Kidney. Neural crest cells invade
the metanephroi early in their development. Neural crest cells give rise to the neurons of the
kidney that regulate blood flow and secretory function. These neurons are located at the tips of
the metanephric tissue caps during nephron induction. Thus these neurons also play a role in
the induction of nephron formation.
9
Anomalies during kidney ascent
Inferior
mesenteric
artery
~22 days
Kidneys ascend from a sacral to lumbar location.
During the 6th to 9th weeks the kidneys ascend to a lumbar site just below the suprarenal
glands. They follow a path on either side of the dorsal aorta (Fig 10-8). The mechanism
responsible for the relocation of the kidneys is poorly understood. The differential growth of
the lumbar and sacral regions of the embryo may play a role. The ascending Kidney is
progressively revascularized by a series of arterial sprouts from the dorsal aorta, and the
original renal artery in the sacral region disappears (Fig 8-6).
Note: The right kidney usually does not rise as high as the left kidney because of the liver on
the right side.
Anomalies can arise during the ascent of the kidneys:
1. Some of the transient inferior renal arteries occasionally fail to regress. This results in
the presence of accessory renal arteries.
2. Also, rarely, a kidney completely fails to ascend, remaining as a pelvic kidney (Fig 10-8C).
3. A U-shaped horseshoe kidney (crosses over the ventral side of the aorta) may also arise if
the inferior poles of the two metanephroi fuse during the ascent. This causes the kidney to
become caught under the inferior mesenteric artery and subsequently it does not reach its
normal site (Fig 10-8D).
10
The remainder of the urinary tract develops
from the hingut endoderm
Cloacal expansion and partition
4th week
Female
Male
Vestibule of
vagina
Penile
urethra
Membranous
urethra
membranous
& prostatic
urethra
6th week
The remainder of the urinary tract develops form the hindgut endoderm.
Cloacal expansion and partition:
As mentioned last week, the cloacal expansion of the hindgut is partitioned by
the urorectal septum into an anterior primitive urogenital sinus and a
posterior rectum (Fig 10-9). The primitive urogenital sinus is continuous
superiorly with the allantois (a hindgut diverticulum that extends into the
umbilicus) and is bounded inferiorly by the urogenital membrane. The
primitive urogential sinus consists of a superior presumtive bladder, pelvic
urethrea (the narrow neck), and an inferior definitive urogenital sinus.
In males, the pelvic urethra becomes the membranous and prostatic
urethra and the definitive urogenital sinus becomes the penile urethra.
In females, the pelvic urethra becomes the membranous urethra, and the
definitive urogenital sinus becomes the vestibule of the vagina.
11
Exstrophy of the mesonephric ducts and
ureteric buds.
*
*
*
*
4-6 weeks
*
*
**
-Endoderm grows over trigone
-Splanchnopleuric mesoderm associated
with the hindgut forms the smooth
muscle of the bladder wall.
Exstrophy of the mesonephric ducts and ureteric buds (Fig 10-10).
*During weeks 4 to 6, via the process of exstropy, the distal portions of the
mesonephric ducts and attached ureteric ducts become incorporated into the
posterior wall of the presumptive bladder (Fig 10-10). Exstropy refers to
the eversion of a hollow organ. During this process the mouths of the
mesonephric ducts flare, expand, flatten, and blend into the bladder wall. This
process brings the openings of the ureteric buds into the bladder wall, while
the opening of the mesonephric duct is carried inferiorly to the level of the
pelvic urethra. The mesonephric ducts open into the pelvic urethra just below
the neck of the bladder.
*The triangular region of exstrophied mesonephric duct, which was
incorporated into the posterior bladder wall, forms the trigone of the bladder.
Endoderm from the surrounding bladder wall grows over the trigone, but it
remains visible in the adult as a smooth triangular region lying between the
openings of the ureters laterally and superiorly, and the opening of the pelvic
urethra inferiorly. During the 12th week, Splanchnopleuric mesoderm
associated with the hindgut forms the smooth muscle of the bladder wall.
12
Ureteric bud or metanephros induction defects
Renal agenesis
A. Defects in the inductive interaction between the ureteric bud and
metanephric blastema may cause renal agenesis.
B. Bilateral renal agenesis results in death. Unilateral renal agenesis
results in hypertrophic kidney.
C. 75% of the cases involving renal agenesis occur in males.
D. Bilateral renal agenesis can also result in oligohydramnios, causing
Potter’s syndrome (deformed limbs and facial defects.
E. Unilateral renal agenesis is usually associated with heart defects
and constrictions of the gastrointestinal tract.
Ureteric bud or metanephros induction defects.
1. Renal agenesis.
a. Defects in the inductive interaction between the ureteric bud and
metanephric blastema may cause renal agenesis.
b. In the absence of inductive signals from the ureteric bud, the metanephros
fails to develop. Infants with bilateral renal agenesis are stillborn or die
within a few days after birth. If unilateral renal agenesis occurs the
remaining kidney will become hypertrophic to compensate for the missing
kidney.
c. 75% of the cases involving renal agenesis occur in males.
d. Renal agenesis typically causes other congenital defects. Since the kidneys
initially contribute to the production of amniotic fluid, bilateral renal
agenesis results in oligohydramnios. The insufficient amniotic fluid causes
the uterine wall to compress the growing fetus, resulting in Potter’s syndrome
(deformed limbs and facial defects—receding chin, low set ears, and parrotbeak nose).
e. Unilateral renal agenesis is usually associated with heart defects and
constrictions of the gastrointestinal tract.
13
Genital System Development
4-6 weeks
~12 weeks
Dental Human Embryology Course (DENT 5315/OBIO-8024)
Brad Martinsen, Ph.D. (marti198@umn.edu)
Lecture 5:
Topic
Assigned Reading
Renal Development
pages 265-276
Genital Development
pages 276-288
The PowerPoint notes pages give a complete review of the reading
assignments (Larson’s Human Embryology, 3rd ed.) and what I will say in
lecture. You can also refer to the Larson’s Human Embryology Website
(http://cna.uc.edu/embryology/) and click on contents for Animations,
Updates, Self-tests, and Glossaries of Terms for each Chapter.
*Use reading assignments to clarify anything said in lecture or in the
notes.
Not all detail in the reading assignments will be on the exams.
14
The genital and urinary systems develop in
close conjunction
Primitive sex cord & Paramesonephric duct
development
(mullerian)
5-6 weeks
Third thoracic segment
caudally to the posterior
wall of the urogenital sinus
The genital and urinary systems develop in close conjunction.
Review note: During the 5th week, the primordial germ cells migrate from the yolk sac via
the dorsal mesentery to the mesenchyme of the posteriror body wall (10th thoracic level) (Fig
10-11A). The primordial germ cells induce cells in the mesonephros and adjacent coelomic
epithelium to proliferate and form the genital ridges (Fig 10-11B,C & 10-12).
Primitive sex cord development.
As mentioned above the primitive sex cords develop from mesonephros cells and coelomic
epithelium cells. During the 6th week, these cells invade the region of the presumptive
gonads to form the primitive sex cords which completely invest the germ cells (Fig 10-11B).
At this point the sex cords have a cortical and medullary regions. After the 6th week these
regions pursue different fates in the male and female.
Paramesonephric duct (Mullerian) development.
During the 6th week, a thickend region of coelomeic epithelium (from the third thoracic
segment caudally to the posterior wall of the urogenital sinus) undergoes craniocaudal
invagination (Fig 10-11B,C), forming the paramesonephric (mullerian) ducts just lateral to
the mesonephric ducts in both male and female embryos. These ducts are enclosed in the
basement membrane of the adjacent mesonephric ducts. The caudal tips of the
paramesonephric ducts connect with the pelvic urethra (the tips adhere to each other before
they connect) just medial to the openings of the right and left mesonephric ducts, while the
superior ends form funnelshaped openings into the coelom.
15
Virtually identical male and female genital
systems.
6th week
At this point the sex
cords have both a
cortical and medullary
region. After the
6th week these regions
pursue different fates in
the male and female.
Virtually identical male and female genital systems (before end of 6th
week).
*In both sexes, germ cells and sex cords are present in both the cortical and the
medullary regions of the presumptive gonads.
*Complete mesonephric and paramesonephric ducts are present.
*After the end of the 6th week the ambisexual or indifferent phase of genital
development ends.
*7th week, the male and female systems follow diverging pathways.
16
Basis of sex differentiation
Autosomes and Sex Chromosomes
1. There is a total complement of 46 chromosomes, 22 pairs consist of matching
homologous chromosomes called autosomes. The 23rd pair are called the sex
chromosomes because they determine the sex of the individual.
2. XX individuals are genetically female.
XY individuals are genetically male.
Subsequent phases of sexual development are controlled by both the sex
chromosome genes and by the hormones and factors encoded by the
autosomes.
3. The sex-determining region of the Y chromosome (SRY) encodes a
transcription factor that controls the choice between the male and female
developmental paths.
Basis of sex differentiation.
Autosomes and Sex Chromosomes:
*There is a total complement of 46 chromosomes, 22 pairs consist of
matching, homologous chromosomes called autosomes. The remaining two
chromosomes are called the sex chromosomes because they determine the sex
of the individual.
*XX individuals are genetically female and XY individuals are genetically
male. Although the pattern of sex chromosomes determines the choice
between male and female developmental paths, the subsequent phases of
sexual development are controlled by both the sex chromosome genes and
by the hormones and factors encoded by the autosomes.
17
Basis of sex differentiation
Autosomes and Sex Chromosomes
4. Male development is triggered when SRY is expressed in the sex cords
during the indifferent phase.
5. Thus the male pathway is actively
induced.
*The sex-determining region of the Y chromosome (SRY) encodes a
transcription factor that controls the choice between the male and female
developmental paths. When SRY is expressed in the sex cord cells (in the
indifferent phase) male development is triggered (Fig 10-13).
18
Figure 10-13
Differentiation cascade of male genital system development.
19
Male genital (internal) Development
Sertoli cell differentiation in the medullary
sex cords
~7th week
Male genital (internal) development.
Sertoli cell differentiation in the medullary sex cords:
1. The SRY protein causes cells within the medullary region of the primitive sex cords to
begin to differentiate into Sertoli cells, while the cells of the cortical sex cords degenerate
(Fig 10-13 & 10-14).
2. If SRY is absent the sex cords develop into ovarian follicles.
3. 7th week differentiating Sertoli cells organize to form the testis cords (Fig 10-14). Also,
the testis begins to round up, reducing its area of contact with the mesonephros (a feminizing
influence). As the testes continue to develop, the degenerating cortical sex cords become
separated from the coelomic epithelium by the tunica albuginea (intervening connective
tissue).
4. At pubery testosterone surge the testis cords and associated germ cells become
canalized and differentiate into the seminiferous tubules. The distal testis cords develop
lumina and differentiate into a set of thin-walled ducts called the rete testis.
5. The tubules of the rete testis become connected with 5 to 12 residual mesonephric
tubules. The mesonephric ducts become the spermatic ducts or vasa deferentia (vas
deferens, singular).
20
Male genital (internal) Development
Anti-Mullerian hormone (AMH) secretion
by Sertoli cells
(reminant of
~8-12th week
cranial end
of mesonephric duct)
Sertoli
Cells
Ductuli efferentes
(reminant of inferior
mesonephric tubules)
Anti-Mullerian hormone secretion by the pre-Sertoli cells:
1. As the Sertoli cells begin to differentiate in response to the SRY protein, they also begin to
secrete anti-Mullerian hormone (AMH) or Mullerian-inhibiting substance (MIS)
(glycoprotein). The protein region resembles the transforming growth factor-beta molecule
which has been implicated in mesoderm induction and angiogenesis.
2. 8th to 10th weekAMH causes the paramesonephric (mullerian) ducts to regress in
the male (Fig 10-13 &10-14).
3. Paramesonephric duct remnants go on to form the appendix testis and utriculus
prostaticus in the adult male. In female embryos, the paramesonephric ducts do not regress.
4. 9th week the SRY protein (expressed by the pre-Sertoli cells) also initiates a cascade
that induces the differentiation of mesenchymal cells within the genital ridges into
testosterone-secreting Leydig cells (in the testis) (Fig 10-13).
5. The Leydig cells (endocrine cells) produce testosterone and this early secretion is regulated
by chorionic gonadotropin, secreted by the placenta (later in development the pituitary
gonadotropins of the male fetus take over control).
21
Male genital (internal) Development
Differentiation of the mesonephric ducts of
the male
~10th-12th week
Differentiation of the mesonephric ducts of the male:
1. 8th to 12th week, the initial secretion of testosterone stimulates the
mesonephric ducts to transform into the spermatic ducts (vasa deferentia)
(Fig 10-14).
2. The most cranial end of each mesonephric duct degenerates into the
appendix epididymis.
3. The region of the vas deferens adjacent to the presumptive testis
differentiates into the convoluted epididymis.
4. During the 9th week, 5 to 12 mesonephric ducts in the region of the
epididymis make contact with the cords of the future rete testis. 3rd month,
these epigenital mesonephric tubules actually unite with the presumptive
rete testis. After uniting the epigenital mesonephric tubules are then called the
ductuli efferentes. They provide a pathway from the seminiferous tubules and
rete testis tubules to the vas deferens.
5. The mesonephric tubules at the inferior pole of the developing testis
(paragenital mesonephric tubules) degenerate into the paradidymis.
22
Male genital (internal) Development
Differentiation of the accessory glands of
the male urethra
~10th-12th weeks
Differentiation of the accessory glands of the male urethra:
1. Three accessory glands of the male genital system all develop near the junction between the
mesonephric ducts and the pelvic urethra (Fig 10-15).
2. 10th week, The glandular seminal vesicles sprout from the distal mesonephric duct near
their attachment to the pelvic urethra. The portion of the vas defenens (mesonephric duct)
distal to each seminal vesicle is called the ejaculatory duct.
3. 10th week, The prostate gland develops from a cluster of endodermal evaginations that
bud from the pelvic urethra (induced by dihydrotestoterone). The initial prostatic
outgrowths form five solid prostatic cords. By the 11th week, the cords develop a lumen and
glandular acini (the surrounding mesenchyme differentiates into the smooth muscle and
connective tissue of the prostate) and by the 13th to 15th weeks, as the testosterone
concentrations reach a high level, the prostate begins to secrete.
4. 10th week, The paired bulbourethral glands sprout from the urethra (inferior to the
prostate). The mesenchyme surrounding the endodermal glandular tissue differentiates into
the smooth muscle and connective tissue of the bulbourethral gland.
Note: The secretions of the seminal vesicles, prostate, and bulbourethral glands all contribute
to the seminal fluid that protects and nourishes the spermatozoa after ejaculation (not
absolutely necessary for sperm function).
23
Female genital (internal) development
Absence of a Y chromosome
Female genital (internal) development.
Absence of a Y chromosome:
1. The female sex cord cells do not express SRY protein (they do not contain the Y
chromosome/SRY region) and thus do not differentiate into Sertoli cells. As a result, AMH,
Leydig cells, and testosterone are not produced. The formation of male structures are not
induced, causing the embryo to follow the default pathway of female development (Fig 10-16).
2. In genetic females, the primitive sex cords degenerate and the mesothelium of the genital
ridge forms secondary sex cords which invest the primordial germ cells to form the follicle
cells of the ovary (Fig 10-16).
Review note: The female germ cells enter meiosis, but further development is inhibited by the
follicle cells. In males, the pre-Sertoli cells inhibit germ cell development before they enter
meiosis. In the female fetus, the germ cells differentiate into oogonia and enter the first
meiotic division as primary oocytes. The follicle cells then arrest germ cell development until
puberty. The close contact of the genital ridge and mesonephros in females is important
for inducing the initial stages of gamete maturation.
24
Female genital (internal) development
Absence of AMH in the female embryo
Absence of AMH in the female embryo:
1. The mesonephric ducts and mesonephric tubules require testosterone for
their development. Thus, in the female, they rapidly disappear, forming
two remnants, the epoophoron and paroophoron (found in the mesentery
of the ovary). Also, a scattering of tiny remnants called Gartner's cysts
cluster near the vagina (Fig 10-16, 10-17C)
2. The paramesonephric ducts develop uninhibited.
25
Female genital (internal) development
Absence of AMH in the female embryo
3. The wall of the pelvic urethra (where the growing tips of the
paramesonephric ducts adhere) forms a slight thickening called the sinusal
tubercle (Fig 10-17A). While fusing with the sinusal tubercle the caudal tips
of the paramesonephric ducts fuse in a superior direction (3rd to 5th month),
forming the genital canal or uterovaginal canal (superior portion of the
vagina and uterus) (Fig 10-17B,C).
4. The superior portions of the unfused paramesonephric ducts become the
fallopian tubes (oviducts), and the funnel-shaped superior openings of the
paramesonephric ducts become the infundibula of the oviducts (Fig10-16).
5. Also during the 3rd month, the thickening endodermal tissue of the sinusal
tubercle in the posterior urethra forms a pair of swellings called the
sinuvaginal bulbs (gives rise to the inferior 20 percent of the vagina)(Fig
10-17).
6. The vaginal plate (of unkown origin, occludes the most inferior region of
the uterovaginal canal) elongates and becomes canalized by a process of
desquamation (cell shedding) to form the inferior vaginal lumen (3rd to 5th
month).
26
Female genital (internal) development
Absence of AMH in the female embryo
7. While the vaginal plate forms, the lower end of the vagina lengthens
caudally until it reaches the posterior wall of the definitive urogenital sinus
(4th month) (Fig 10-17C).
8. An endodermal membrane temporarily separates the lumen of the vagina
from the cavity of the definitive urogenital sinus (vestibule of the vagina).
After the 5th month, this membranes degenerates into the vaginal hymen.
27
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