Reproduction and development

Question 1

What are the external female genital structures?

Answer 1

Vulva consists of:
- mons pubis (protection)
- labia majora (protection and arousal)
- labia minora (protection)
- clitoris (arousal)
- vestibular bulbs (arousal)
- vulvar vestibule (entrance to vagina and urethra)
- Bartholin glands (lubrication of vagina during arousal)
- Skene’s glands (lubrication of urethra, female ejaculation)

Question 2

What are the internal female genital structures?

Answer 2

1) vagina
2) cervix
3) cervical cavity
4) uterus (womb) covered with endometrium (uterine lining) with uterine cavity inside
5) pair of fallopian tubes
6) pair of ovaries (connected to uterus with fallopian tubes and ovarian ligaments)

Question 3

What are the features of ovaries?

Answer 3

• 2-4 cm long elliptical structure
• thick cortex filled with follicles (capsules of egg cells): most of ovary
• each follicle is surrounded with granulosa cells and than theca cells
• small central medulla contains nerves and blood vessels
• stroma (connective tissue)

Question 4

How many oogonia gets to the stage of primary oocytes?

Answer 4

500 000 primary oocytes (immature egg cells) from 7 million oogonia (female germ cells).

Question 5

What are the stages of ovum/follicle development in ovaries?

Answer 5

1) primordial follicle

2) primary follicle

3) growing secondary follicle with oocyte inside

4) follicle bursts, releasing ovulating ovum with corona radiata

5) developing corpus luteum

6) developed corpus luteum

7) corpus albicans (degenerated corpus luteum)

Question 6

What are the features of female meiosis?

Answer 6

Meiosis I starts in fetal/prenatal state (before female was even born) and ends at ovulation. Formation of the first polar body.

Meiosis II starts after ovulation and ends after fertilization. Formation of the second polar body.

Question 7

What is hormonal regulation of reproductive system in both sexes?

Answer 7

Hypothalamic-anterior pituitary pathway:

1) Hypothalamus sends gonadotropin releasing hormone to anterior pituitary. The secretion is pulsatile (every 90 minutes).

2) Anterior pituitary sends follicle stimulating hormone and luteinising hormone to gonads.

3) gonads secrete sex steroids (oestrogen, progesterone and testosterone) for themselves and many other tissues; also inhibit hypothalamus and anterior pituitary via negative feedback loop.

Gonads also produce inhibin, activin, follistatin and anti-Mullerian hormone.

Placenta releases chorionic gonadotropin and placental lactogen.

Question 8

How reproduction related hormones activate their targets?

Answer 8

Through G-coupled protein –> G protein activating adenylate cyclase –> adenylate cyclase producing cAMP:
follicle stimulating hormone, luteinising hormone, activin, inhibin and anti-Mullerian hormone.

Through cytoplasm and nuclear receptors (dimerized hormone-receptor complex binds to response element before TATA-box, becoming a part of a diverse complex of transcription factors): all sex steroids.

Question 9

What is hormonal regulation of reproductive system, specific for females?

Answer 9

Follicle stimulating hormone targets granulosa cells, so they produce follicles and inhibin to inhibit anterior pituitary gland.

There are bidirectional signals between granulosa cells and germ cells.

Luteinizing hormone targets thecal cells, so they produce testosterone (immediately converted to oestrogen with aromatase in follicular/granulosa cells) during follicular phase or progesterone during luteal phase to target the rest of the body and inhibit anterior pituitary gland.

Question 10

What are the phases of ovarian cycle?

Answer 10

Lasts 24-35 days.

1) follicular phase (10-21 days):
- 6-12 primary follicles develop with FSH trigger;
- LH stimulates production of oestrogen in thecal cells (as testosterone) and follicular cells (converted to oestrogen with aromatase);
- at day 6, only one follicle is left, the rest are degenerated (atresia)
- oestrogen and inhibin inhibit FSH but not LH
- oestrogen rapidly increases and peaks just before ovulation to stimulate endometrium growth
- cervical mucus becomes thin: more permeable to sperm

2) ovulation (egg release from ovary):
- oestrogen feedback on pituitary switches to positive, so more LH and FSH are produced
- LH and FSH peak
- LH triggers egg and antral fluid release 16-24 hours later with collagenase
- meiosis I ends
- egg with cumulus oophorus (some former granulosa cells) enter fallopian tubes
- thecal cells stay in ovary and produce progesterone

3) luteal phase (ruptured follicle transforms into corpus luteum):
- thecal cells and remaining granulosa cells form corpus luteum
- corpus luteum produces second but smaller peaks for progesterone and oestrogen to still support endometrium growth
- it makes LH and FSH to do lowest

Next cycle is triggered by progesterone and oestrogen decline to slowly increase LH and FSH again.

Question 11

What are the phases of uterine cycle?

Answer 11

Aligns with ovarian cycle, also lasts 24-35 days.

1) menses (menstruation):
- discharge of blood and endometrium

2) proliferative phase (corresponds to follicular phase, thickening of endometrium to prepare uterus to potential embryonic implantation)
- oestradiol stimulates growth of endometrium

3) secretory phase (corresponds to luteal phase, endometrium is the thickest up to 2 cm, ready to embryonic implantation)
- progesterone stimulates secretion of nutrients from endometrium to feed potential embryos.

Question 12

What are the hormonal changes at menopause?

Answer 12

The levels of follicle stimulating hormone and luteinising hormones are kept constantly very high because low oestradiol levels cannot inhibit their production.

Oestradiol levels are very low because depletion of eggs (follicles) ceases menstrual cycle, so thecal cells do not receive enough signals to produce oestradiol and progesterone.

Oestradiol deficiency is responsible for most menopause symptoms, so it is treated with this hormone and sometimes with progestin.

Question 13

What are the components of male reproductive system in the order of sperm production and flow?

Answer 13

1) Testis (production of sperm cells/spermatozoa and testosterone secretion)

2) Epididymis (storage and maturation of sperm cells; sac just above testes with very convoluted tubules, releases phosphorylcholine)

3) ductus/vas deferens (connects testes to urethra)

4) ampulla (thicker parts on the end of ductus deferens; secretion and storage of semen by adding ergothioneine for chemical protection and fructose for sperm nourishment)

5) seminal vesicle (releases 60-70% of the fluid for semen, contributes prostaglandins, fructose, lipids, has antimicrobial properties)

6) ejaculatory duct

7) prostate gland (releases 25-30% of seminal fluid, contributes citric acid, spermine, prostatic acid phosphatase, zinc)

8) prostatic urethra

9) bulbourethral glands (lubrication of urethra) and urogenital diaphragm (support) around membranous urethra

10) penile urethra inside bulb, crus, spongy tissue (corpus cavermosum outside and corpus spongiosum inside) and glans. Spongy tissue contains blood vessels which fill with blood during erection.

Question 14

What are the components of testes?

Answer 14

INTERSTITIAL (INTERTUBULAR) COMPARTMENT (contains lots of tubules in stroma)
- Leydig cells (clustered around vessels/tubules): triggered by luteinizing hormone to produce testosterone to act on Sertoli cells. Testosterone inhibits pituitary and hypothalamus from secreting more LH.
- Leydig cells also regulate testicular immune environment
- 4-10 mg of testosterone is secreted per day.

SEMINIFEROUS TUBULE COMPARTMENT
- testosterone accumulates there (and in interstitium) in high concentrations

• Sertoli cells (on germinal epithelium): spermatogenesis (hold developing sperm cells like Christmas tree), release transporting androgen-binding protein (80% for testes in luminal fluid and 20% for systemic circulation) and paracrine signals to induce spermatogenesis.
• Sertoli cells are activated by follicle stimulating hormone and thyroid hormone, release inhibin to inhibit pituitary release of FSH.
• maturing sperm cells (spermatogenesis): spermatogonium, primary spermatocyte, secondary spermatocyte and spermatids. Earlier stages are on basal membranes of seminiferous tubules, later are closer and closer to the tubule centre.

Question 15

Why testes are located outside body?

Answer 15

Seminiferous epithelium (particularly beta-polymerase and spermatogenic recombinase) is very sensitive to temperatures close to 36 degrees C and above. Optimal temperature required is ~34 degrees C.

Question 16

What are the structural features of Leydig cells?

Answer 16

• lots of smooth endoplasmic reticulum
• lots of mitochondria

Both needed to synthesise lots of lipids (steroid hormones).

Question 17

What are the structural features of Sertoli cells?

Answer 17

• Large cytoplasm
• oval nucleus with distinctive dark nucleolus

Question 18

What is the difference between spermatogenesis and spermiogenesis?

Answer 18

Booth take place in seminiferous tubules (testes) and both are continuous processes (do not take place in cycles like in female reproduction).

Spermatogenesis is the first stage, results in spermatids.

Spermiogenesis in the next stage, results in mature sperm cells

Question 19

What is the male meiosis?

Answer 19

1) Spermatogonia and primary spermatocytes are diploid

2) Meiosis I makes 2 secondary spermatocytes

3) Meiosis II makes 4 spermatids (embedded on apical membrane of Sertoli cells before maturation), which mature into spermatozoa.

Whole process takes 64 days.

Question 20

What is sperm structure?

Answer 20

Head:
- very compact nucleus just to carry genetic material (histones are replaced with protamines)
- no cytoplasm to decrease as much mass for fast movement as possible
- acrosome on the top contains enzyme to digest zona pellucida of the egg cell

Midpiece:
- spiral mitochondria to generate energy for movement

Tail (axial filament):
- connected microtubules slide with energy of ATP to generate corkscrew movement

Question 21

What is the role of tight junctions in testes?

Answer 21

Sertoli cells are connected to each other with tight junctions (which break and reform to release maturing sperm) and desmosomes, forming blood-testis barrier.

Question 22

Are there any embryological histological analogies between ovaries and testes?

Answer 22

Yes.

Granulosa cells correspond to Sertoli cells. Both:
- develop gametes
- depend on FSH

Thecal cells correspond to Leydig cells. Both:
- produce hormones used by granulosa and Sertoli cells
- depend on LH
- use 17beta hydroxysteroid dehydrogenase to produce testosterone.
(except thecal cells divide every month; Leydig cells divide only at fetal stage and puberty)

Question 23

What are the key differences between ovaries and testes?

Answer 23

Ovaries:
- monthly cycle of the release on the single egg cell, corresponding to endometrium development
- finite reproductive lifespan (menopause is present)
- meiosis starts in embryonic state.
- produces oestrogen and progesterone; their levels depend on the stage of cycle (oestradiol peaks on follicular phase, lots of oestradiol and progesterone at luteal phase).

Testes:
- continuous production of 50-100 million of viable sperm cells per day
- fertility present even in the very old age
- meiosis does not start until puberty
- produces androgens, their levels depends on the time of the day (highest on the morning, lowest in the night)

Question 24

What are the differences at germ cell lineages in females and males?

Answer 24

Females (oocyte lineage):
- mitosis: only in fetus
- no proliferating stem cells in adults: results in limitation to how many eggs can be made, hence limited reproductive lifespan;
- meiosis: meiosis I starts in fetus (prophase I), ends at ovulation (after puberty); meiosis II starts after ovulation; ends after fertilisation (long term blocks for meiotic exit in both divisions); egg cell does not actually exist as a separate haploid cell.

Males (spermatocyte lineage):
- mitosis: starts at fetus, stops and resumes at puberty
- stem cells are present in adults, they proliferate to produce new germ cells.
- meiosis: no in fetus, begins only at puberty after long-term block from fetal mitosis (long term block from meiotic entry); meiosis I and II are completed before release; exists as a free-living haploid cell.
Male germ cells cease proliferation in fetus and remain quiescent until puberty.

Question 25

What are the consequences of androgen deficiency?

Answer 25

Caused by Leydig cells producing not enough androgens despite continuous stimulation with LH. Sertoli cells are not sufficiently stimulated with androgens hence germ cells end up having: - reduced mitosis - meiosis does not progress - less spermatids elongate - premature cell shedding (round spermatids enter semen with normal sperm) Overproduction of LH leads to: - overproliferation of immature Leydig cells - decrease in amount of mature Leydig cells

Question 26

Why testosterone intravenous injections do not increase male fertility but actually decrease it further?

Answer 26

Testosterone levels in testes are 100 times higher than in systemic circulation: IV injection cannot mimic that. However, testosterone at systemic circulation goes good job at further inhibiting pituitary gland release of LH that actually stimulates Leydig cells to produce testosterone. More systemic testosterone --> less LH --> less testicular testosterone --> decreased fertility due to immature sperm.

Question 27

What is the role of retinoic acid (vitamin A) in male fertility?

Answer 27

Activates male germ cells to undergo mitosis and then meiosis by expressing gene STRA8 (meiosis committing gene) in spermatogonia and spermatocytes. Prolonged deficiency of retinoic acid results in absence of all lineage (mostly meiotic cells) except just self-renewing (committing to continue to be stem cells) stem cells.

Question 28

Is retinoic acid (vitamin A) involved in female fertility?

Answer 28

Yes, but only during fetal phase. Meiotic genes (STRA8, SYCP3, DMC1) are expressed at ovaries during female fetal development (indicating their meiosis indeed starts at fetal state) but not expressed in male fetal development (indicating their meiosis indeed does not start in fetal state). Knocking out Aldh1a1 (another gene expressed with help of retinoic acid) in female foetuses delays commitment to meiosis.

Question 29

Where do the final stages of sperm maturation happen?

Answer 29

Outside of semiferous tubules: 1) sperm washes into the rete (the network of tubules just above semiferous tubule lobules. Here sperm can twitch only. 2) enter epididymis through efferent ductile. Here sperm can already swim. This maturation depends on androgen stimulation.

Question 30

What are the function of male accessory glands?

Answer 30

They produce seminal fluid to: - nourish sperm - protect its DNA from damage (antioxidants). - buffering again vaginal acidic pH - Flush of seminal fluid also protects against infections by flushing and having immune cells.

Question 31

What is the chemical composition of seminal fluid and from which accessory glands they come from?

Answer 31

Ejaculation: about 3 (1.5-5 range) ml of seminal fluid. Epididymis: - glycerophosphocholine (the product of cell membrane breakdown of the maturing sperm shrinking its cell content) - alpha-glucosidase (breaks down carbohydrates; used as a marker for semen quality, correlates to sperm count) - L-carnitine (antioxidant) Seminal vesicles: - Fructose (to generate ATP from oxidative phosphorylation and hence keep sperm alive and motile) - semenogelin (gel/coagulum coat to temporary inhibit sperm motility; associated with Zn ion) - prostaglandins (PGE support sperm motility, PGF induce peristaltic contraction of uterus to facilitate sperm delivery) - fibrinogen - vitamin C and hypotaurine (antioxidants) - fibrinectin (sperm capacitation) Prostate: - prostate specific antigen (protease which cleaves semenogelins; used to determine prostate cancer) - other KLKs - Zn2+ to associate with semenogelin - Citrate (unclear function, probably involved in sperm capacitation) Cowper's gland: - mucin (moisturise urethra, facilitate semen flow)

Question 32

What are the cellular components of semen?

Answer 32

- mature sperm - some of round immature sperm (elevated in infertile men) - epithelial cells of urogenital tract (vas deferens, urethra etc) - leukocytes (this is how HIV can be transmitted during intercourse)

Question 33

What is the % contribution of male accessory glands to seminal fluid production?

Answer 33

Seminal vesicles - 65-85% Prostate - 25-30% Testes and epididymis - 10% Bulbourethal gland - 1%

Question 34

How does endocervix (channel that connects vagina with uterus) help with sperm propagation?

Answer 34

- cyclical secretion of mucous; its fibrils help to guide spermatozoa - estrogen makes mucous more watery, so sperm can enter during ovulation (~day 9) - progesterone inhibits secretion of mucous - sperm storage in endocervical crypts - protection against immune attack - nourishing - initiation of capacitation

Question 35

How do other female structures limit sperm entry?

Answer 35

1) Vagina: low pH (3.8-4.5) - chemical sperm selection (normally acidic vagina is a barrier for infections) 2) muscular sphincter on cervix: physical sperm selection

Question 36

How much sperm manages to pass cervix and actually enter uterus?

Answer 36

Only 1%. 99% stuck in cervical mucous, stay in vagina or leak out.

Question 37

What is capacitation?

Answer 37

Making sperm head more uncovered, unstable and leaky, so it can easy fertilize the egg cell. It involves: - cholesterol loss destabilises membrane - near corona radiata, acrosome releases enzymes acrosin and hyaluradinase to digest zona pellucida - activates phospholipases which change membrane composition and expose inner phospholipids, further destabilizing membrane - motility increases ("whiplash" hypermotility)

Question 38

How does sperm increase its pH?

Answer 38

Albumin removes cholesterol from sperm cell membrane, so it becomes more permeable to Ca2+ and bicarbonate ion.

Question 39

How does fertilization occur?

Answer 39

1) only ~100 sperm cells reach the egg cell at distal part of Fallipian tube 12-24 hours after ovulation. 2) acrosome releases enzymes to digest zona pellucida 3) membranes fuse and the sperm nucleus enters the ovum; sperm enzyme PLC triggers Ca2+ oscillations. 4) triggered with Ca2+, female meiosis II ends with release of the second polar body 5) cortical reaction (hardening of the egg cell membrane with Ca2+ triggered exocytosis of granule content) prevents polyspermy (entrance more than one sperm cell)

Question 40

What are the features of embrio development days 1-5?

Answer 40

Day 1: - distal ends in fallopian tube - first cleavage (2 blastomeres) Day 2: - remains in fallopian tube - second cleavage (4 blastomeres) - polar body degeneration Day 3: - third cleavage (8 blastomeres) - beginning of compaction (cells bind tightly to each other because they finaly expressed proteins to form tight junctions) Day 4: - formation of morula due to the end of compaction. Cells cannot be visually seen as separate anymore, only with staining separate cells are visible. - 16-32 blastomeres - beginning of differentiation because there are clearly cells facing outside and cells locked inside. Cells inside recieve signals to secrete fluid. Day 5: - Formation of blastocyst: the first wave of differentiation, there are the inner cell mass (bulb on the side from inner cells) and trophectoderm from outside cells (hollow bubble with fluid cavity called blastocoele). - embryo expands - embryo reaches the uterus - zona pellucida thins and stretches, blastocyte hatches from zone pellucida (squeezes out from hole in it) at days 5-7.

Question 41

When and how does implantation happen?

Answer 41

When blastocyst fully hatched out from zona pellucida in secretory phase of uterine cycle (when the endometrium in the thickest), corresponds to day 7-8. In this way, it can communicate with endometrium to invade (burrow into it) and attach to it. Stages: 1) apposition (contact with endometrium): both uterus and blastocyst express CSF-1 to cross-talk; prostaglandin E2 increases endometrial vascular permeability. 2) adhesion: IL-1, IL-6 and HB-EGF are adhesion factors; cell adhesion molecules are integrins, E-cadherin (Ca2+ dependent), L-selectin. 3) invasion: - trophoblasts (cells from trophectoderm) grow into endometrium with chorionic villi (finger-like projections) and fuse with local spiral blood vessels (to feed placenta on the future); - extracellular matrix is degraded with serine proteases (mostly collagenases) from trophoblasts to provide space for invasion; - decorin prevents invasive trophoblasts overgrowth.

Question 42

Which embryos are transferred in case of artificial fertilisation?

Answer 42

Embryos are graded (checked for quality) before day 4 (in morula, you cannot judge clearly): - if blastocyte number correspond to their stage and this number develops in time - if blastocytes are the same size (different sizes means something is very wrong) - if blastocytes are less than 10% fragmented (over 25% fragmentation is poor quality embryo) - multinucleation absent - blastocyte size corresponds to their stage Embryos are also graded at blastocyte stage (day 5): - if inner cell mass and trophectoderm are well defined, organised, uniform and compact - blastocyte is fully expanded with thinning zona pellucida or even hatched away from it The best artificial embryos are implanted at second, third or fifth day after fertilization, depending on method/protocol.

Question 43

May embryologists assist with blastocyst hatching?

Answer 43

Yes, by manually thinning zona pellucida or drilling a hole in it in mechanical or chemical way or with laser.

Question 44

What does happen during implantation stage (days 8-9)?

Answer 44

Inner cell mass: - becomes fetus - secretion of amiotic fluid from amnion (membrane around fetus) - chorion is the outermost membrane - allantois is the middle membrane (looks like sac below Yolk sac), which becomes part of umbilical cord - Yolk sac with nutrients Trophectoderm: - becomes placenta - involved in invasion during implantation.

Question 45

Do maternal and fetus circulation mix?

Answer 45

No, they come close together but never mix (but there is gas and nutrient exchange). However, placenta feeds from both maternal and fetal circulation. Foetus gets up to 10% of maternal cardiac output.

Question 46

What are the hormonal changes during pregnancy?

Answer 46

Endometrium (uterine lining) has to be maintained for 9 month straight. No endometrium shading - no menstruation. First trimester: - corpus luteum still present and continues to secrete progesterone (to a bigger extend) and oestradiol (to a less extend) - the presence of corpus luteum more than normal 12 days is triggered not by LH, but with human chorionic gonadotrophin (hCG) from placenta, which is a structural analogue of LH (use the same receptors) Second and third trimester: - corpus luteum degenerates; - placenta itself secretes oestrogen and progesterone to maintain endometrium (self-sustained) and prevent new follicle development in ovaries; - human placental lactogen (human chorionic somatomamotrophin) changes mother's glucose and fatty acid metabolism to support fetal growth and prepare to lactation after giving birth. Its levels related to fetal health. - oestrogen prepares to lactation (development of milk secreting ducts)

Question 47

What are the additional features of human chorionic gonadotrophin?

Answer 47

Triggers testosterone production in male fetuses. Basis for pregnancy test.

Question 48

What are the stages of parturition (birth)?

Answer 48

Trigger of birth: - foetus drops head down - hormonal signals are unclear, probably oxytocin or corticotrophin releasing hormone are involved Labour (rhythmic uterine contractions): 1) relaxin make cervix and pelvic ligaments softer; 2) cervical stretch leads to uterine contraction, triggering oxytocin release from posterior pituitary; 3) positive feedback loop: oxytocin (by activating prostaglandins and corticotrophin releasing hormone) further increases intensity of uterine contraction, which triggers posterior pituitary again, releasing even more oxytocin leading to more and more uterine contractions. Delivery: - baby gets out, connected to placenta - placenta gets out after

Question 49

What are the potential of embrionic cells to diffentiate (embrionic cell potency)?

Answer 49

Fate choice plays a crucial role in embryo development. Zygote is totipotent - can develop into organism, placenta or differentiating into any tissues (all 220 cell types). Inner mass cells are pluripotent: may develop in any cell types (endoderm, mesodern, ectoderm lines) in body only (not into placenta). The cell lineages which differentiate into just different cells in a single tissue (such as haempoietic stem cell) are multipotent.

Question 50

What does happen with embryo at days 9-23?

Answer 50

Day 9 (second wave of differentiation): - the part of inner cell mass closer to trophoblasts becomes epiplast; - the part of inner cell mass closer to fluid becomes hypoblast; - may still happen during implantation. Before day 12: - hypoblast cells spread on the walls of trophoblasts to form one inner sac. They will form gut line. - the cells inside epiblast secrete fluid again to form another inner sac. They will form skin and nerves. - this results at bilaminal disk (2 sacs inside of trophoblasts) Day 12 (third wave of differentiation): - between disks (cells at the point of their contact), mesoderm appears - outer epiblast cells become ectoderm - outer hypoblast cells become endoderm Day 18: - mesoderm speads to cover all surfaces around exoderm, endoderm and trophoblasts - all layes fold on themselves to become a tube-like closed system Day 23: - tube folds longitudinally to form head end, tail end and yolk sac in between; - yolk sac provides nutrients before embryo develops its own circulation - formation of umbilical cord - amniotic sac (the membrane between fetus and placenta) and amniotic fluid develops to do shock absorption and protect fetus. Most of the organs come from further complicated folding.

Question 51

Which tissues/organs arise from ectoderm?

Answer 51

- Skin (epidermis) and its derivatives (hair, nails, external glands) - Nervous system (neural tube into CNS and neural crest into PNS and glial cells) - pituitary - apical ectodermal ridge: outlining of limbs (limb buds)

Question 52

What tissues arise from endoderm?

Answer 52

All epithelia (such as respiratory tract lining, gut lining, endothelium) and associated organs (except skin), pharyngeal pouches. From digestive tube, the following organs develop: - liver - gallbladder - pancreas - respiratory tube which bifurcates into 2 lungs - pharynx connects digestive and respiratory tubes Pharyngeal pouches partially give rise to: - middle ear - tonsils - thymus gland - thyroid gland

Question 53

What tissues arise from mesoderm?

Answer 53

Bulky organs/tissues: - muscles - bones - heart - connective tissue - cartilage - blood - bone marrow - lymphoid tissue - kidneys - adrenal cortex - genitalia (gonads) - blood vessels outside of endothelium

Question 54

How is neural tube formed?

Answer 54

Exoderm invades mesoderm and "pushes out" a tube by folding on itself.

Question 55

Which organs system develops during all 3-38 weeks of pregnancy?

Answer 55

Central nervous system, followed by eyes (eyes start to develop at week 4). Ears also develop for quite long time. Heart, arms and legs end developing at week 9. Teeth, palate and external genitalia are last to develop.

Question 56

How it was proved that testes contained an important hormone (testosterone) which influences male phenotype?

Answer 56

1) By castration before puberty in humans (in male opera singers so they sing with high voice to the end of their life). 2) By castration of bulls - made them less agressive. 3) Arnold Berthold transplanted testes to female chicken and castrated roosters and noticed changes in appearence and behavior. 4) Fred Koch and Lemuel McDee took extract of bull testes and showed it makes castrated roosters more masculine. In 1930s, testosterone was purified and its structure determined.

Question 57

Who first postulated the existence of hormones?

Answer 57

Charles-Edouard Brown-Sequard discovered that removing adrenal glands is letal.

Question 58

When does sexual development of embryo starts?

Answer 58

Not earlier than 6th week. Before that, gonades are undifferentiated and it is impossible to physically observe the gender. There are ovary/testis precursors and two sets of tubes: - Mullerian ducts - Wolffian ducts

Question 59

Where do gonades develop in embryo?

Answer 59

At genital ridge at mesonephros, consisting of coelomic epithelia, mesenchyme and primordial germ cells.

Question 60

How does male genitalia develop in fetuses?

Answer 60

There is SRY gene on the tip of Y chromosome, which encodes transcription factors for expression of SOX9, and both SRY (with SF-1) and SOX9 turn on thousands of testicular genes (formation of semiferous tubules) and turn off ovarian genes. Wolffian ducts develops into epididymis, vas deferens and seminal vesicles by the action of testosterone from Leydig cells. Mullerian duct degenerates by the action of anti-Mullerian hormone secreted by fetal Sertoli cells. It was proved by Alfred Jost by implanting both testis and ovary (resulted in the same testes action) and by implantation testosterone crystal (resulted in both Mullerian and Wolffian tubes continuing to exist). Male differentiation happens early - first trimester.

Question 61

How does female genitalia develop in fetuses?

Answer 61

No SRY gene mean ovary genes are not repressed and testes genes are not activated. Primary sex chords degenerate and secondary sex chords (egg nests) take their place. Mullerian ducts develops into fallopian tubes, uterus and vagina. Wolffian ducts degenerate by default. This was proved by Alfred Jost by removing gonads. Female differentiation happens late.

Question 62

What are other features of anti-Mullerian hormone?

Answer 62

- one of the transforming growth factor beta. - homodimeric glycoprotein - also expressed in females but in much lower amounts - in females, AMH is a marker of granulusa cells tumor, polycystic tumors and ovarian age - normal AMH levels = success of in vitro fertilization

Question 63

What is Freemartin syndrome?

Answer 63

Female cows are born infertile, with non-functional ovaries and masculinised features due to having male twin that shared AMH and testosterone to his sister. Тhis repressed female reproductive system development. Exchange of cells from male twin to female results in chymeric freemartin cow (mix of XX and XY cells, especially in blood). John Hunter showed the cause of freemartin syndrome.

Question 64

Which syndromes prove Y chromosome is sex determining?

Answer 64

Turner syndrome - only one X chromosome - results in female. Klinefelter syndrome - XXY - results in male. Means Y chromosome causes production of testosterone and AMH in testes.

Question 65

Why meiosis cannot happen in males before puberty?

Answer 65

In testes, peritubular myoid cells produce enzyme CYP26B1 which degrades retionic acid. As a result, cells stay as stem cells. During puberty and after, retinoic acid is produced by Sertoli cells themselves.