What you'll learn
Fertilisation, development and control of fertility follows the events from the meeting of sperm and egg through to birth, and then examines how fertility can be reduced or assisted. At CAPE level you must know the mechanisms preventing polyspermy, the sequence of early cleavage and implantation, the structure and function of the placenta, and the hormonal control of pregnancy and birth. By the end of this topic you should be able to describe capacitation and the acrosome reaction, explain how polyspermy is prevented, describe cleavage and implantation, relate placental structure to its exchange function, explain the hormonal control of pregnancy and parturition, and evaluate methods of contraception and assisted reproduction.
Key terms and definitions
Capacitation — changes to the sperm membrane in the female tract that enable it to fertilise
Acrosome reaction — the release of hydrolytic enzymes from the sperm acrosome
Cortical reaction — the release of cortical granule contents that prevents further sperm entering
Polyspermy — fertilisation by more than one sperm, which is fatal to the zygote
Zygote — the diploid cell formed by fusion of the two gamete nuclei
Cleavage — the series of rapid mitotic divisions with no growth between them
Morula — the solid ball of cells formed by early cleavage
Blastocyst — the hollow ball of cells that implants in the endometrium
Implantation — the embedding of the blastocyst in the endometrium
Trophoblast — the outer layer of the blastocyst, which forms the placenta
Chorionic villi — the finger-like projections of the placenta that increase surface area
Human chorionic gonadotrophin — the embryonic hormone maintaining the corpus luteum
Parturition — the process of birth
Core concepts
Capacitation and the approach to the egg
Sperm deposited in the vagina are not immediately capable of fertilisation. During their passage through the female reproductive tract they undergo capacitation: glycoproteins and cholesterol are removed from the sperm cell surface membrane, which makes the membrane more fluid and more permeable to calcium ions.
Only a few hundred of the several hundred million sperm released reach the oviduct. Movement is assisted by the beating of the flagellum, by peristaltic contractions of the uterus and oviduct, and by prostaglandins in the semen that stimulate those contractions.
Sperm are attracted towards the oocyte by chemicals it releases, moving up the concentration gradient by chemotaxis.
The acrosome reaction and fertilisation
On reaching the oocyte, the sperm first encounters the corona radiata, the layer of follicle cells, and then the zona pellucida, a glycoprotein layer.
The sperm binds to species-specific receptor proteins on the zona pellucida. This binding triggers the acrosome reaction: the acrosome membrane fuses with the sperm cell surface membrane and releases hydrolytic enzymes.
These enzymes digest a path through the zona pellucida, allowing the sperm to reach the egg cell surface membrane.
The membranes of the sperm and the egg then fuse, and the sperm nucleus enters the cytoplasm of the oocyte. The sperm tail and mitochondria are excluded or degraded, which is why mitochondrial DNA is inherited only from the mother — a point worth knowing since it is frequently asked.
Entry of the sperm stimulates the secondary oocyte to complete its second meiotic division, producing the mature ovum and the second polar body. Only then do the two haploid nuclei fuse to form the diploid zygote nucleus.
Preventing polyspermy
If more than one sperm fertilised the egg, the resulting cell would have too many chromosomes and would not develop. Two mechanisms prevent it, and both should be given.
The fast block is an immediate depolarisation of the egg cell surface membrane on fusion with the first sperm, which prevents further sperm from fusing.
The slow block is the cortical reaction. Cortical granules lying beneath the egg membrane fuse with it and release their contents into the space around the egg. These contents alter the glycoprotein receptors of the zona pellucida so that no further sperm can bind, and cause the zona to harden, forming a physical barrier. This is the more important and longer-lasting mechanism.
Cleavage and implantation
The zygote begins a series of rapid mitotic divisions called cleavage. No growth occurs between divisions, so the cells become progressively smaller and the total mass is essentially unchanged. This is why the egg needed so much cytoplasm: it supplies all the material for these early divisions.
After about three days a solid ball of cells, the morula, has formed. It continues to move down the oviduct towards the uterus, propelled by cilia and peristalsis.
By about day five the morula has become a blastocyst: a hollow ball with a fluid-filled cavity, an outer layer called the trophoblast, and an inner cell mass that will form the embryo itself.
At about day six to seven the blastocyst implants, embedding in the thickened endometrium. The trophoblast cells secrete enzymes that digest the endometrial tissue, and the blastocyst sinks into it.
The trophoblast then secretes human chorionic gonadotrophin, which maintains the corpus luteum so that progesterone secretion continues and the endometrium is retained rather than shed.
The placenta
The placenta develops from the trophoblast together with maternal tissue, and it is the organ of exchange between mother and fetus.
Chorionic villi project from the placenta into blood-filled spaces in the endometrium. They provide an extremely large surface area for exchange, and their walls are thin, giving a short diffusion distance between fetal and maternal blood. Fetal capillaries lie close to the surface of each villus, and the maternal blood in the spaces is continually replenished, so concentration gradients are maintained.
Substances passing from mother to fetus include oxygen, glucose, amino acids, fatty acids, water, mineral ions, vitamins and antibodies. Substances passing from fetus to mother include carbon dioxide, urea and other waste.
Transport occurs by several mechanisms: diffusion for oxygen and carbon dioxide, facilitated diffusion and active transport for glucose and amino acids, and pinocytosis for antibodies.
Crucially, the two blood supplies do not mix. This matters for three reasons that are examinable: maternal blood pressure would damage the delicate fetal vessels; the blood groups may be incompatible; and separation reduces the transfer of pathogens and of maternal immune cells that might attack fetal tissue.
Efficient transfer is also aided by fetal haemoglobin, which has a higher affinity for oxygen than adult haemoglobin, so its dissociation curve lies to the left. This allows the fetus to take up oxygen from maternal blood at the relatively low partial pressure found in the placenta.
The placenta also acts as an endocrine organ, taking over the secretion of progesterone and oestrogen from the corpus luteum after about twelve weeks.
Not everything is excluded. Alcohol, nicotine, many drugs and some pathogens including rubella virus and HIV can cross the placenta, which is why these are avoided in pregnancy.
Hormonal control of pregnancy and birth
Progesterone dominates pregnancy. It maintains the endometrium, inhibits FSH and LH so that no further cycles occur, and inhibits contraction of the uterine muscle, keeping the uterus quiescent.
Oestrogen concentration also rises through pregnancy, stimulating growth of the uterus and of the mammary glands.
Towards the end of pregnancy the balance shifts: oestrogen concentration rises relative to progesterone, which increases the sensitivity of the uterine muscle and prepares it to contract.
Parturition is triggered as oxytocin is released from the posterior pituitary. Oxytocin stimulates contraction of the myometrium, and this is the standard example of positive feedback in the syllabus.
The mechanism is worth stating carefully. Contractions push the fetus against the cervix, stretching it. Stretch receptors in the cervix send impulses to the hypothalamus, which stimulates the posterior pituitary to release more oxytocin. More oxytocin produces stronger contractions, which stretch the cervix further, which causes still more oxytocin to be released. The cycle amplifies until the fetus is expelled, at which point the stimulus is removed and the cycle ends. Because the response amplifies the original change rather than reversing it, this is positive feedback.
Prolactin from the anterior pituitary stimulates milk production after birth, and oxytocin also causes milk release during suckling, again by positive feedback while suckling continues.
Control of fertility
Contraceptive methods fall into several categories, and evaluation questions expect both effectiveness and drawbacks.
Hormonal methods, including the combined pill, progesterone-only methods, implants and injections, work chiefly by inhibiting FSH and LH through negative feedback so that ovulation does not occur, with additional effects on cervical mucus and the endometrium. They are highly effective when used correctly and are reversible, but require consistent use, may cause side effects, and give no protection against infection.
Barrier methods, including condoms and diaphragms, prevent sperm reaching the egg. Condoms additionally reduce the transmission of sexually transmitted infections, which no other method does, but they must be used correctly every time.
Intrauterine devices prevent implantation and may release copper, which is toxic to sperm, or progesterone. They are effective for several years but may cause heavier menstruation.
Surgical methods — vasectomy and tubal ligation — are highly effective and permanent, and should be regarded as irreversible.
Natural methods rely on identifying the fertile period using the calendar, basal body temperature, which rises about 0.5 degrees Celsius after ovulation, and changes in cervical mucus. They have no side effects and are acceptable where other methods are not, but they are considerably less reliable because cycles vary.
Assisted reproduction
In vitro fertilisation is used where the oviducts are blocked or where other treatments have failed.
The woman is given FSH to stimulate the development of several follicles simultaneously, a process called superovulation. The oocytes are collected, mixed with sperm in the laboratory, and the resulting embryos cultured for a few days. One or more embryos are then transferred to the uterus, and progesterone is given to support the endometrium.
Where sperm are few or immotile, a single sperm may be injected directly into the oocyte.
The advantages are that it allows conception where it would otherwise be impossible, and that embryos can be screened for genetic disorders before transfer.
The disadvantages and ethical issues include the low success rate per cycle, the physical and emotional demands of treatment, the risk of multiple pregnancy where several embryos are transferred, ovarian hyperstimulation syndrome caused by the drugs, the high cost and unequal access, and disagreement about the status and fate of surplus embryos.
Worked examples
Example 1: Explaining the prevention of polyspermy (5 marks)
Explain how the entry of more than one sperm into an egg is prevented, and why this matters.
If two sperm entered, the resulting cell would contain three sets of chromosomes rather than two. The chromosomes could not be distributed correctly at mitosis, and the embryo would not develop.
Two mechanisms prevent it. Immediately on fusion of the first sperm with the egg cell surface membrane, the membrane depolarises, which prevents any further sperm from fusing with it. This is a rapid but temporary block.
The longer-lasting mechanism is the cortical reaction. Cortical granules lying just beneath the egg membrane fuse with it and release their contents into the surrounding space. These substances alter the glycoprotein receptors on the zona pellucida so that no further sperm can bind to it, and they cause the zona pellucida to harden, forming a physical barrier that sperm cannot penetrate.
Example 2: Relating placental structure to function (5 marks)
Explain three features of the placenta that allow efficient exchange between mother and fetus.
The placenta bears numerous chorionic villi, finger-like projections extending into blood-filled spaces in the endometrium. These give a very large surface area over which exchange can occur, increasing the rate of diffusion.
The walls of the villi are thin, and the fetal capillaries lie close to the surface, so the diffusion distance between fetal and maternal blood is very short, which again increases the rate of diffusion.
Maternal blood in the spaces is continually replenished and fetal blood is continually circulated, so steep concentration gradients for oxygen, glucose, carbon dioxide and urea are maintained across the exchange surface.
In addition, fetal haemoglobin has a higher affinity for oxygen than adult haemoglobin, so it takes up oxygen from maternal blood even at the relatively low partial pressure found in the placenta.
Example 3: Explaining positive feedback in birth (4 marks)
Explain how oxytocin acts by positive feedback during labour.
Uterine contractions push the head of the fetus against the cervix, causing it to stretch.
Stretch receptors in the cervix send nerve impulses to the hypothalamus, which stimulates the posterior pituitary gland to release oxytocin into the blood.
Oxytocin travels to the uterus and stimulates the myometrium to contract more strongly, which pushes the fetus harder against the cervix and stretches it further.
The greater stretch causes still more oxytocin to be released, so the contractions become progressively stronger and more frequent. Because each response amplifies the change that produced it rather than reversing it, this is positive feedback. The cycle continues until the fetus is expelled, removing the stimulus.
Common mistakes and how to avoid them
The most frequent error is stating that the sperm fertilises a mature ovum. A secondary oocyte is fertilised, and it completes meiosis only after the sperm enters.
Students often say that maternal and fetal blood mix in the placenta. They remain separate, and three reasons — blood pressure, blood group incompatibility and pathogen transfer — should be available.
Another common slip is describing cleavage as growth. Cleavage divisions produce progressively smaller cells with no increase in total mass.
Many candidates give only one mechanism preventing polyspermy. Both the membrane depolarisation and the cortical reaction are expected.
In parturition questions, answers frequently describe oxytocin without identifying the feedback as positive or explaining why. The amplification is what defines it.
Finally, candidates often confuse the trophoblast with the inner cell mass. The trophoblast forms the placenta; the inner cell mass forms the embryo.
Exam technique for "Fertilisation, development and control of fertility"
Describe fertilisation as a numbered sequence — capacitation, chemotaxis, binding, acrosome reaction, membrane fusion, completion of meiosis, nuclear fusion — since marks follow the stages.
For the placenta, structure the answer around surface area, diffusion distance and concentration gradient, exactly as for any other exchange surface.
When feedback is mentioned, state which type and justify it by saying whether the response reverses or amplifies the change.
In contraception questions, group methods by how they act — preventing ovulation, preventing fertilisation, preventing implantation — and note which also protects against infection.
For evaluation of IVF, give at least two advantages and two disadvantages including an ethical point, and finish with a judgement.
Quick revision summary
Sperm are capacitated in the female tract, attracted by chemotaxis, and bind to receptors on the zona pellucida, triggering the acrosome reaction in which hydrolytic enzymes digest a path to the egg membrane. Membrane fusion causes immediate depolarisation and the cortical reaction, which alters and hardens the zona pellucida, together preventing polyspermy. The sperm nucleus enters, the oocyte completes meiosis II, and the haploid nuclei fuse to form a diploid zygote. Cleavage produces progressively smaller cells forming a morula and then a blastocyst, whose trophoblast implants in the endometrium and secretes hCG to maintain the corpus luteum. The placenta bears chorionic villi giving a large surface area, thin walls giving a short diffusion distance, and maintained concentration gradients, with maternal and fetal blood kept separate because of pressure, blood group and pathogen considerations, and fetal haemoglobin's higher affinity aiding oxygen uptake. Progesterone maintains pregnancy and inhibits contractions until oestrogen rises relative to it; oxytocin then drives labour by positive feedback through cervical stretch receptors. Contraception acts by inhibiting ovulation hormonally, by barrier, by intrauterine device, surgically or by natural fertility awareness, and IVF uses FSH superovulation followed by laboratory fertilisation and embryo transfer.