1. Female Reproductive Embryology
Lance Paulman, Ph.D.
Office Room 142
Phone

2. Reading Moore & Persaud; The Developing Human, 8th ed.; pp 262—284
Review the Urinary Embryology lecture by Dr. Abdellatif

3. Take home points
Renal and reproductive embryology have a lot of overlap
Mesonephric and paramesonephric ducts will contribute to reproductive structures
Germ cells arise from outside the developing embryo and have to migrate into the embryo as the gonads form
DEFAULT CONDITION IS FEMALE
Sexual differentiation is hormone driven in males
Germ cell are not part of the embryo
Migrate into the embryo from extra embryonic tissues
No testosterone = no males

4. Take home points
Early stage gonadal development is virtually identical in males and females
Indifferent gonad forms first—epithelium and mesenchyme from the medial mesonephros
GONADAL RIDGE
Epithelial cords will grow into the gonads
Now have CORTEX and MEDULLA (sound familiar?) – kidneys, adrenal medulla

5. The IMPORTANT Part
Early stage embryogenesis during the lateral folding portion, where folding the edges of the embryo down and forming the yolk sac and importing part of it into the body to form the GI tract = primordial germ cells migrating in
They migrate in with the yolk sac, and then through the dorsal mesentery into the gonadal ridges
Must have the mesonephric and paramesonephric systems if going to form functional system

6. Primordial Germ Cells
Recognizable at 4th week among cells of endoderm of yolk sac
Migrate into embryo during folding; part of the umbilical vesicle which will form GI tract
6th week migrate into mesnchyme and are incorporated into gonadal cords
Males – gonadal cords persist
Females – gonadal cords break down

7. Early differentiation
Developing of the gonadal ridge, germ cells migrating in  forming gonadal cords

8. Germ Cells
Showing germ cells being incorporated into the gonadal cords, the part that will become the medulla (females should come from the cortex…not the medulla?)
Note paramesonephric and mesonephric ducts are in close opposition to the developing gonad
- Will form the tubes and structures by which fertilization can take place

9. The Indifferent Gonad At this stage the gonads are the same
in male and
female
Stained photomicrograph of what will form the gonadal ridge
Mesenchymal stuff – forms medulla
- The larger cells you see = primordial germ cells (undifferentiated, so do not know whether will be spermatogonia or oogonia yet)

10. Development of the Ovary
Ovaries develop later than testes ~ 10th week
Ovaries are derived from the cortex of the indifferent gonad
Medullary tissue regresses ALMOST completely
Gonadal cords form rudimentary rete ovarii, then degenerate
Epithelial cells migrate into ovary, form cortical cords
Will form follicles that make up most of the ovary
The developmental delay of the ovaries in comparison to the testes persists until menstruation kicks in
Note testes are derived from the medulla and we loose almost all of the cortex in that situation
rete ovarii = straight tubes of the ovary  break down and go away

11. Early ovarian stage IS NOT under hormonal control
Primordial germ cells migrate into gonadal cords in both sexes. Note position of
mesonephric and paramesonephric ducts. Hard to tell the difference at this age
Biggest difference here is the SRY region on the short arm of the X chromosome (pretty sure it’s Y)
This produces testes determining factor (TDF)  if secrete this will be male, and a lack of this secretion = female
The lack of hormones causes ovarian development

12. Later stage ovary Gonadal cords are regressing. Primordial
germ cells migrating into
cortical cords
Medulla degenerating
At ~ 16 weeks cortical cords
break up into primordial
follicles—one germ cell and
single surrounding layer of
epithelial cells—this goes on
throughout fetal period
Former gonadal cords and medulla breakdown
Have epithelial cells forming cortical cords – germ cells migrate into this
16th week  cortical cords start to break down  each primordial germ cell forms a follicle that will be surrounded by a layer of epithelial tissue = primordial follicle
This continues all the way through the fetal period  end up with millions of primordial follicles
Some undergo primary mitosis, the others degenerate and go away
So, all follicles have undergone primordial mitosis by the time a female is born and will stay that way until stimulated by hormones

13. Late stage ovary Primary mitosis occurs ONLY during
fetal period. None happens postnatally
Surface epithelium (single cell layer) is
continuous with the peritoneum at the
hilum of the ovary
THIN tunica albuginea forms to separate
follicles from surface epithelium
Now you are ready for the next stage…
After you are born, no primary mitosis takes place
Surface epithelium (single cell layer) is
continuous with the peritoneum at the
hilum of the ovary is an important concept because When follicle undergoes ovulation and ruptures into the outside world, outside the ovary it is inside the peritoneal space
Tunica albuginea is thick in males because the sperm need to stay there. In females it is very thin because the follicle needs to rupture to release the eggs

14. Descent of gonads!! Soon to be a major motion picture!!
Both ovaries and testes migrate from the posterior abdominal wall toward the pelvis
Guiding influences include hormones, degeneration of duct systems, and the
GUBERNACULUM; connective tissue structure that runs from gonad to anterior
abdominal wall; becomes caught in developing uterus in females—becomes
suspensory ligament of the ovary and round ligament of the uterus
The ovaries and testes migrate down all the way from the posterior abdominal wall to the labial or scrotal swelling.
Males descends all the way = short piece of gubernaculum left over = testicular ligament
Gonad is never inside the peritoneal space = always outside the peritoneum
Passes posterior to it, underneath, and along it
Extension of the peritoneal space = processes vagnalis  intrudes down and forms the inguinal canal
In males passes across the pubic bone and then down and out into the testes

15. Ligamentous Remnants of the Gubernaculum
Paramesonephric ducts remain intact, fuse together, and form the uterovaginal primordium
When that starts to grow to develop the uterus and the vagina  starts to envelop the gubernaculum
Gets caught up in the wall of the uterus
The portion that attaches the ovaries to the uterus = ovarian ligament
The portion that attaches from the uterus to the labial folds and passes through the inguinal canal = round ligament of the uterus

16. The SCARY Part
Now that you have a gonad, you have to have a way for it to connect to the outside world
In females, this means formation of uterine tubes, uterus and the vagina
Connecting structures derive from mesonephric and paramesonephric duct systems
Uterine tube literally connects peritoneum to the outside world through vagina
- Infections can travel intraperitoneally and give you peritonitis

17. Female ducts Mesonephros REQUIRE testosterone to survive
Regress in females
Paramesonephros will form most of the duct system
Very little testosterone is produced in a female

18. Primitive ducts… Indifferent stage Both duct systems present Note
connection
to UG sinus
Paramesonephric duct  developes fimbriae of the uterine tube
Fuses together
Connects to the urogenital sinus  becomes the bladder, allantois, etc…
At the sinual tubercle, between the paramesonephros and the urogenital sinus  will have what becomes the uterus and part of the vagina
Mesonephros breaks down

19. Later….
Cranial portion of PM ducts remains unfused; open to peritoneal space—these become
uterine tubes. Caudal portion fuses, forms uterus and upper 2/3 of vagina. Note
remnants of mesonephic ducts in mesovarium
Most of the uterus and part of the vagina develop from the paramesonephric system
Can see remnants of the mesonephros in the broad ligament of the uterus
- Form little chunks of tissue = epoephron of peroopheron

20. Accessory Glands in Females
Urethral and paraurethral glands develop from the urethra—mucus secreting glands
Greater vestibular glands develop from buds off the urogenital sinus—will inhabit lower 1/3 of labia majora—analogs to bulbourethral gland in males
Urethral and paraurethral glands develop from the endoderm surrounding the urethra — mucus secreting to keep nasty critters from getting in there (prevent against UTIs)
Greater vestibular glands – makes sex easier. No need to sing paulman. No need.

21. Later….
Shows the glands budding off

22. Overview of all this stuff
Sinovaginal bulb  becomes the lower part of the vagina
Developing ovaries next to the paramesonephric ducts
Uterus  at some point was two tubes, so must fuse and septatation must break down

23. Formation of the vagina
Upper 2/3 or so from paramesonephric ducts
Lower vagina from mesenchyme between uterovaginal primordium and UG sinus
SINOVAGINAL BULBS—VAGINAL PLATE
Central cells break down,down, forming lumen of vagina
Sinovaginal bulbs = expansions of the wall of the urogenital sinus  fuse to form the solid vaginal plate  eventually central cells will break down and form the lumen of the vagina

24. Fused paramesonephric ducts— UTEROVAGINAL PRIMORDIUM
Connect to UG sinus—
stimulates growth of
sinovaginal bulb
Sinovaginal bulb starts to develop a solid tissue structure  assume a lower portion to create the cervix then…. (See next slide)

25. Fused sinovaginal bulbs form VAGINAL PLATE; central cells break down to form lumen

26. Variation, of course….
What you end up with

27. As this is a complex structure, requiring the correct function
of many different
parts, things can go
wrong…..
Never fuse the paramesonephric ducts together = bicornuate uterus.
B – vagina is septated, because the sinovaginal bulbs never completely broke down
C – no septum in the vagina
Both of these are reproductively functional, but do not necessarily have enough room in the wall to grow a baby
D – partially septated uterus  distal part broke down but the proximal part didn’t
E – one of the paramesonephric ducts just didn’t form very well
F - septate uterus
G – one of the paramesonephric ducts just didn’t form at all
- No ovary here either, and the ovary migrating into it’s proper position has a lot to do with the ducts maintaining itself

28. Formation of the External Genitalia
ALMOST identical in males and females…
Thank goodness for the differences….
Position of urethra, fusion of labioscrotal folds, migration of gonads major differences
Position of urethra because phallic primordium doesn’t consume the urethra.
- In females the urethra is not contained in the clitoris (doesn’t completely envelop it)

29. Cannot tell difference between male and female at this stage
Genital tubercle – forms penis, glands of penis, and glands of clitoris
Labialscrotal swelling
Cloacal membrane  gets divided up into the cloaca (urogenital membrane) and anus
Perineal body holds it all together

30. Urethral groove in females opens up to the surface and remains open
Labial scrotal folds start to fuse together posteriorly, but only fuse for a sort distance and then stops  leaves you with a frenulum = a little piece of tissue that holds something in place
Outer swelling  becomes labia marjoram
Inner swelling  labium minus
The cloacal opening = vaginal introits

31. Surrounding the vaginal orifice is a remnant of the vaginal plate because the outermost layer of cells stays behind covering up the opening of the vagina = hymen

32. Notes on the Vaginal Plate and the Vaginal Lumen
As the vaginal lumen forms, a thin layer of tissue remains over the opening of the vagina—the hymen
GREAT deal of potential variation here
Can be clinically important

33. Variations in hymen formation
Normal case – relatively large vaginal opening an a normal hymen covering the orifice
Incomplete perforation – much smaller opening
Septate – parallel openings
Cribiform – lots of little punctate openings
Microperforate – super small hole
Imperforate – no hole
Can cause issues because at the onset of menses  gets blocked up  will decay
When baby is born and if not imperforate they just make a hole
Because of all the issues – indeterminate genitalia is an major issue

34. Inquiries????
Until next time, then, Docs!!!