Gametogenesis and fertilisation
Gametogenesis, fertilisation, implantation and placenta: FCPS embryology
Spermatogenesis and oogenesis, fertilisation in the ampulla, implantation in week 2 and the structure and functions of the placenta for FCPS Part 1. Covers meiotic arrest, hCG, the placental barrier, abnormal placentation, vasa praevia and germ cell migration.
Primordial germ cells
- Germ cells arise in the wall of the yolk sac near the allantois in week 4 and migrate along the dorsal mesentery of the hindgut to the genital ridges by week 6. Without them the gonad does not develop properly.
- Germ cells that stray from this midline route can survive and later form extragonadal germ cell tumours, typically in the midline: anterior mediastinum, pineal region, retroperitoneum and sacrococcygeal area (teratoma in newborns). A mediastinal seminoma with normal testes is explained this way.
- Pure seminoma does not raise AFP; a raised AFP means non-seminomatous elements (yolk sac tumour).
Gametogenesis
| Feature | Spermatogenesis | Oogenesis |
|---|---|---|
| Starts | Puberty, continuous for life | Fetal life: oogonia multiply, then enter meiosis I before birth |
| Meiotic arrest | None | Primary oocyte in diplotene of prophase I until ovulation; secondary oocyte in metaphase II until fertilisation |
| Products per precursor | Four sperm | One ovum plus polar bodies |
| Duration | About 64–74 days (commonly quoted as 64), plus transit through the epididymis | Up to 40–50 years of arrest |
| Numbers | Millions a day | About 7 million at 5 months of fetal life, 1–2 million at birth, about 400,000 at puberty, about 400 ovulated |
- The longer an oocyte waits in prophase I, the higher the risk of nondisjunction (Down syndrome rises with maternal age; most cases arise in maternal meiosis I).
- Spermiogenesis turns round spermatids into sperm without division: the acrosome forms from the Golgi apparatus, the flagellum from a centriole, and most cytoplasm is shed as residual bodies.
- Capacitation in the female tract (about 7 hours) removes surface glycoproteins so the sperm can undergo the acrosome reaction.
Hormonal control of spermatogenesis
| Hormone | Target | Role |
|---|---|---|
| LH | Leydig cells | Testosterone production; intratesticular levels are many times higher than in blood |
| FSH | Sertoli cells | Androgen-binding protein, support of germ cells; inhibin feeds back on FSH |
| Testosterone | Sertoli cells (locally) | Needed in high local concentration for spermatogenesis |
- Exogenous testosterone or anabolic steroids suppress GnRH, LH and FSH by negative feedback. Blood testosterone is high but intratesticular testosterone falls, so spermatogenesis stops: small soft testes, azoospermia, very low LH and FSH. Giving more testosterone worsens it; stopping the drug usually allows recovery.
Fertilisation
- Usually in the ampulla of the uterine tube, within about 24 hours of ovulation (the ovum survives 12–24 hours; sperm about 3 days).
- Steps: sperm pass the corona radiata (hyaluronidase); bind ZP3 of the zona pellucida; undergo the acrosome reaction (acrosin digests the zona); sperm and oocyte membranes fuse; the cortical (zona) reaction makes the zona impermeable to other sperm, blocking polyspermy; the oocyte completes meiosis II and releases the second polar body; male and female pronuclei form the zygote.
- Results: restores diploid number, determines chromosomal sex (X or Y sperm), starts cleavage.
Cleavage and implantation
- Zygote, then morula (about 16 cells, day 3–4, enters the uterus), then blastocyst (day 4–5) with inner cell mass (embryoblast) and outer trophoblast. The zona pellucida disappears (hatching) before implantation.
- Implantation starts on day 6–7, usually in the posterior wall of the upper uterine body, and is complete by day 10–12.
- The trophoblast splits into inner cytotrophoblast (dividing cells) and outer invasive syncytiotrophoblast, which secretes hCG. hCG is detectable in blood from about day 8–10 and keeps the corpus luteum producing progesterone until the placenta takes over at about 8–10 weeks.
- Ectopic pregnancy: over 95% in the uterine tube, commonest in the ampulla (about 70%). Risk factors: salpingitis or PID (chlamydia, gonococcus), previous ectopic, tubal surgery, IUCD.
- Placenta praevia: implantation in the lower uterine segment, giving painless bleeding in late pregnancy.
The placenta
- Fetal part: chorion frondosum (villous chorion). Maternal part: decidua basalis. The fetal surface is covered by amnion and is shiny; the maternal surface shows 15–20 cotyledons.
- Villi: primary (trophoblast only), secondary (mesoderm core), tertiary (fetal capillaries) by the end of week 3.
- Placental barrier: early in pregnancy syncytiotrophoblast, cytotrophoblast, connective tissue of the villus and fetal endothelium. At term the cytotrophoblast largely disappears and the barrier thins to syncytiotrophoblast and fetal capillary endothelium.
- At term: about 500 g, 15–20 cm across. The umbilical cord has two arteries (deoxygenated blood to the placenta) and one vein (oxygenated blood, about 80% saturated, to the fetus) in Wharton jelly. A single umbilical artery is linked with renal and cardiac anomalies.
- Hormones: hCG, human placental lactogen (maternal insulin resistance, lipolysis), progesterone, oestriol (needs fetal adrenal and liver).
- Transfer: only IgG crosses (passive immunity, but also anti-D and maternal autoantibodies such as TSH-receptor antibodies). IgM does not. Most drugs cross; heparin and insulin do not. Carbimazole and methimazole cross more readily than propylthiouracil, which is why PTU is used in the first trimester. Mother-to-child HIV transmission is reduced by maternal antiretroviral therapy.
Abnormal placentation and cord
| Condition | Feature |
|---|---|
| Placenta accreta | Villi attach to the myometrium without invading it (decidua basalis deficient; previous caesarean) |
| Increta | Villi invade into the myometrium |
| Percreta | Villi penetrate through the myometrium to serosa or bladder |
| Vasa praevia | Fetal vessels run in the membranes over the internal os, usually from a velamentous cord insertion; they tear at membrane rupture, causing bright red bleeding with fetal bradycardia while the mother stays stable. Antenatal colour Doppler allows planned caesarean |
| Complete hydatidiform mole | 46,XX all paternal (empty egg), no fetus, very high hCG, highest choriocarcinoma risk |
| Partial mole | Triploid (69,XXY), fetal parts present, lower risk |
| Choriocarcinoma | Malignant cytotrophoblast and syncytiotrophoblast, no villi; very high hCG; lung metastases; responds to methotrexate |
Remember Fertilise in the ampulla, implant on day 6–7, hCG from the syncytiotrophoblast.
Exam trap Fertilisation and ectopic pregnancy are both commonest in the ampulla, not the isthmus.
Exam trap Exogenous testosterone causes azoospermia, not better fertility: it lowers intratesticular testosterone by suppressing LH.
How FCPS asks about this
- Stage of oocyte arrest until ovulation: diplotene of prophase I; secondary oocyte waits in metaphase II.
- Duration of spermatogenesis: about 64–74 days; acrosome from the Golgi apparatus.
- Commonest site of fertilisation and ectopic pregnancy: ampulla of the uterine tube.
- Source of hCG: syncytiotrophoblast; fetal part of placenta is chorion frondosum.
- Placental barrier at term: syncytiotrophoblast and fetal capillary endothelium.
- Painless bright red bleeding at membrane rupture with fetal bradycardia: vasa praevia.
- Midline extragonadal seminoma: misplaced primordial germ cells.
Test yourself on this topic
5 of the 44 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A 28-year-old bodybuilder has injected testosterone for two years and now attends the infertility OPD. His testes are small and soft, semen analysis shows azoospermia, and serum LH and FSH are both very low. What is the mechanism of his azoospermia?
Answer: Low intratesticular testosterone from LH suppression
Exogenous testosterone feeds back on the hypothalamus and pituitary, suppressing GnRH, LH and FSH. Without LH, Leydig cells stop producing testosterone, and the very high testosterone concentration needed inside the testis for spermatogenesis is lost, even though blood levels are high from the injections. Low FSH also removes Sertoli cell support. Spermatogenesis stops and the testes shrink; it usually recovers months after stopping.
Steroid-induced azoospermia
- Exogenous testosterone suppresses LH, FSH
- Leydig cells stop: low testicular testosterone
- Spermatogenesis stops
- Usually reversible
Remember Low gonadotrophins and small testes in a bodybuilder: exogenous androgens.
Exam trap Do not treat with testosterone: it makes the problem worse.
Why the other options are wrong
- Direct toxic effect of testosterone on germ cells Testosterone is needed for spermatogenesis, not toxic to it.
- Obstruction of the vas deferens by fibrosis Obstruction gives normal-sized testes and normal hormones.
- Antisperm antibodies after testicular injury Not suggested by the history.
- Primary failure of Sertoli cells in the testis Primary testicular failure would give high LH and FSH.
A woman with two previous caesarean sections has a placenta that will not separate after delivery, and she needs a hysterectomy. Histology shows villi lying directly on the myometrium. What is the underlying defect?
Answer: Deficient decidua basalis
Normally the decidua basalis, with its fibrinoid Nitabuch layer, limits trophoblast invasion and provides a plane for the placenta to separate. Where the endometrium is scarred, as over a caesarean scar or after curettage, the decidua forms poorly. Villi then attach to (accreta), invade (increta) or penetrate through (percreta) the myometrium. With no cleavage plane, the placenta cannot separate and massive haemorrhage can follow.
Placenta accreta
- Deficient decidua basalis
- Risk: previous caesarean, praevia
- Villi on myometrium
- No cleavage plane: haemorrhage
Remember Scarred uterus, no decidua: accreta.
Exam trap Placenta praevia over a caesarean scar carries the highest risk of accreta.
Why the other options are wrong
- Excess syncytiotrophoblast invasion of arteries Spiral artery remodelling is normal and is not the cause.
- Abnormal chorion laeve The smooth chorion forms the membranes, not the attachment site.
- Uterine atony A separate cause of bleeding with normal separation.
- Retained succenturiate lobe An accessory lobe; histology would not show villi on myometrium.
Where does fertilisation usually occur, and what must happen to sperm in the female tract before they can penetrate the zona pellucida?
Answer: Ampulla; capacitation, acrosome
Fertilisation usually occurs in the ampulla, the widest and longest part of the uterine tube, within about 24 hours of ovulation. Capacitation, taking several hours in the female tract, removes glycoproteins and cholesterol from the sperm membrane; the capacitated sperm then binds ZP3 of the zona pellucida, triggering the acrosome reaction, which releases enzymes (acrosin, hyaluronidase) to penetrate it. Fusion of sperm and oocyte membranes triggers the cortical reaction in the oocyte, hardening the zona to block polyspermy, and completion of the second meiotic division. The ampulla is also the commonest site of ectopic pregnancy; implantation normally occurs in the posterior uterine wall around day 6–7.
Fertilisation
- Site: ampulla of uterine tube
- Sperm: capacitation → binds ZP3 → acrosome reaction
- Oocyte: cortical reaction blocks polyspermy; completes meiosis II
- Implantation: day 6–7, posterior uterine wall
Remember Ampulla for meeting; acrosome for entering.
Why the other options are wrong
- Uterus; sperm meiosis Sperm meiosis happens in the testis.
- Isthmus; sperm make the zona Not correct.
- Ovary; cortical reaction in sperm The cortical reaction occurs in the oocyte.
- Cervix; capacitation only Fertilisation is in the tube.
At 6 weeks of pregnancy, a woman needs laparoscopic removal of a twisted ovary that contains the corpus luteum. Which of the following is the most appropriate step afterwards?
Answer: Progesterone support until about 10 weeks
In early pregnancy, hCG from the syncytiotrophoblast keeps the corpus luteum alive, and its progesterone maintains the decidua. The placenta gradually takes over progesterone production between about 7 and 10 weeks (the luteoplacental shift). If the corpus luteum is removed before this, progesterone falls and the pregnancy may miscarry, so progesterone is given until about 10 weeks. After that, removal of the corpus luteum does not threaten the pregnancy.
Luteoplacental shift
- hCG keeps the corpus luteum alive
- CL makes progesterone early
- Placenta takes over at 7–10 weeks
- CL removed early: give progesterone
Remember Corpus luteum lost before 10 weeks: replace progesterone.
Exam trap hCG peaks at about 10 weeks, when the placental takeover is nearly complete.
Why the other options are wrong
- No treatment; the placenta takes over now The placenta is not yet producing enough progesterone at 6 weeks.
- Oestrogen support until delivery Oestrogen does not maintain the decidua in this way.
- hCG injections until 20 weeks hCG cannot act once the corpus luteum is removed.
- Bed rest alone for two weeks Rest does not replace the lost progesterone.
Evacuation for a missed miscarriage at 12 weeks shows swollen villi mixed with normal villi and fetal parts. The karyotype is 69,XXY. How did this conceptus most likely arise?
Answer: Two sperm fertilising a normal ovum
A partial hydatidiform mole is triploid, most often 69,XXY or 69,XXX, with one maternal and two paternal sets of chromosomes. It arises when two sperm fertilise one normal ovum (dispermy), which happens when the block to polyspermy fails. Fetal tissue is present because a maternal genome exists. A complete mole, by contrast, is diploid and wholly paternal, from an empty ovum fertilised by one sperm that duplicates, or by two sperm.
Partial mole
- Triploid: 69,XXY
- Dispermy of a normal ovum
- Fetal parts present
- Lower malignant risk than complete mole
Remember Fetal parts plus molar villi: triploid partial mole.
Exam trap The cortical (zona) reaction normally prevents a second sperm from entering.
Why the other options are wrong
- One sperm fertilising an empty ovum Gives a complete mole, diploid and paternal only.
- Non-disjunction in maternal meiosis I Gives trisomy, not triploidy.
- Duplication of a single sperm genome Gives a 46,XX complete mole.
- Fusion of two fertilised ova Gives a chimera, not triploidy.
Where this sits in the CPSP syllabus
- Paper 1: General and systemic embryology, Gametogenesis, fertilisation, implantation and placenta
- Surgery & Allied, Paper 2: Embryology for surgery, Gametogenesis, fertilisation, implantation and placenta
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