D3.1 Reproduction

Asexual and sexual reproduction

Every living organism eventually dies, so the continuity of a species depends on reproduction. Organisms reproduce in two different ways. In asexual reproduction a single parent produces offspring, and in sexual reproduction two parents each contribute half of the genetic material of the offspring.

How asexual reproduction works

Asexual reproduction uses mitosis in eukaryotes (or binary fission in prokaryotes), so the offspring receive exact copies of the parent's chromosomes. A group of genetically identical organisms produced in this way is called a clone. The only source of genetic difference between them is the occasional mutation during DNA replication.

• Binary fission in bacteria such as Escherichia coli: the cell copies its circular chromosome and divides in two, as often as every 20 minutes in ideal conditions.

• Budding in yeast (Saccharomyces cerevisiae) and in Hydra: a small outgrowth of the parent grows and separates as a new individual.

• Vegetative propagation in plants: strawberry plants (Fragaria × ananassa) send out runners that root and form new plants, and potato plants (Solanum tuberosum) grow tubers that each sprout into a new plant.

• Parthenogenesis in some animals: female aphids produce live young from unfertilised eggs throughout the summer.

How sexual reproduction works

Sexual reproduction involves the fusion of two gametes, one from each parent, to form a single cell called a zygote. Each gamete carries one set of chromosomes, so the zygote receives a mixture of the two parents' alleles. Because each parent can produce gametes with many different combinations of alleles, every offspring (except identical twins) is genetically unique.

Advantages of each method

Each method suits different circumstances. Asexual reproduction is fast and needs only one parent, so a single individual can colonise a new habitat. Its offspring are genetically identical to a parent that has already survived and reproduced, so they are well adapted to the existing environment, as long as that environment stays the same. Sexual reproduction is slower and needs two parents to meet, but it produces offspring with new combinations of alleles. This genetic variation is the raw material for natural selection, so a sexually reproducing population can adapt if the environment changes, for example when a new disease or predator appears or the climate shifts.

Some organisms switch between the two methods to get the benefits of both. Aphids reproduce asexually through spring and summer, when food is plentiful and a rapid increase in numbers pays off. In autumn they produce males and females that reproduce sexually and lay eggs that survive the winter, so the next year's population starts with new combinations of alleles. The risk of relying only on asexual reproduction is shown by the Cavendish banana, which is propagated vegetatively: the plants are genetically identical, so a fungal disease that can infect one plant can infect them all.

Meiosis and fertilisation in the sexual life cycle

A sexual life cycle alternates between two chromosome numbers. Body cells of animals and most plants are diploid (2n), with two sets of chromosomes, one inherited from each parent. Gametes are haploid (n), with one set. In humans, 2n = 46 and n = 23.

Two processes keep the chromosome number constant from generation to generation. Meiosis halves the chromosome number when gametes are made, and fertilisation doubles it again when two gametes fuse. Without meiosis, the chromosome number would double every generation.

How meiosis and fertilisation create new combinations of alleles

Meiosis does more than halve the chromosome number. It breaks up the combinations of alleles that each parent inherited. During meiosis I, crossing over between homologous chromosomes swaps sections of DNA, creating chromosomes with new combinations of alleles. The random orientation of each pair of homologous chromosomes at the equator means that each gamete receives a random mixture of maternal and paternal chromosomes. In humans, random orientation alone allows 2²³ (about 8.4 million) chromosome combinations in each gamete.

Fertilisation then brings together two of these unique gametes, usually from unrelated parents. The zygote therefore has a combination of alleles that has never existed before. Meiosis breaks up parental combinations and fertilisation makes new ones; together they generate the variation on which the continuity and change of a species depend.

Differences between the male and female sexes

In almost all sexually reproducing animals and plants the two gametes are different in size and behaviour. The male gamete moves (or is carried) to the female gamete, so it is small and contains little more than a nucleus and the means to move. The female gamete stays where it is and supplies the food reserves and cytoplasm for the early embryo, so it is much larger. In humans, the egg cell has a diameter of about 0.1 mm and is one of the largest cells in the body, while a sperm cell is about 50 µm long with a head only about 5 µm long.

This difference in gamete size has consequences for the reproductive strategies of the two sexes. A male can produce enormous numbers of cheap gametes, so males of many species compete to fertilise as many eggs as possible, for example with displays, fighting or large numbers of sperm. A female produces few, costly gametes and often invests further in the offspring (in mammals, through pregnancy and milk), so females tend to be selective about mates. Flowering plants show the same pattern: a single anther may release thousands of small pollen grains, but each ovule contains one egg cell and develops into a single seed.

The human male and female reproductive systems

The human reproductive systems are organ systems specialised for producing gametes, delivering them to the site of fertilisation and, in the female, supporting the developing embryo and fetus. Each structure has a specific function, and a good drawing of either system is annotated with those functions as well as the names of the structures.

The male reproductive system

The diagram of the male system shows how sperm travel from where they are made to where they leave the body. Sperm are made in the testes, stored and matured in the epididymis, carried by the sperm duct to the urethra and released through the penis. Fluids from the seminal vesicles and prostate gland mix with the sperm to form semen.

The female reproductive system

The female system produces eggs, receives sperm, provides the site of fertilisation and houses the developing fetus. Eggs develop in the ovaries. After ovulation an egg is swept into the oviduct, where fertilisation usually happens. The embryo then moves down to the uterus and implants in its lining, the endometrium.

The menstrual cycle and its hormonal control

From puberty until the menopause, the female reproductive system goes through a repeating sequence of changes that prepares an egg for fertilisation and the uterus for pregnancy. This menstrual cycle lasts about 28 days on average, although lengths from about 21 to 35 days are normal. It is two linked cycles running together: the ovarian cycle in the ovaries and the uterine cycle in the endometrium.

Four hormones from two glands

Four hormones control the cycle. Two are protein hormones secreted by the anterior lobe of the pituitary gland: follicle-stimulating hormone (FSH) and luteinising hormone (LH). They travel in the blood to the ovaries. The other two are steroid hormones made by the ovaries themselves: oestradiol (the main oestrogen) and progesterone. The pituitary and ovaries regulate each other by feedback, which is why the hormone levels rise and fall in a repeating pattern.

The follicular phase (days 1–14)

Day 1 of the cycle is the first day of menstruation, when the endometrium from the previous cycle is shed. At this time oestradiol and progesterone levels are low, so they no longer inhibit the pituitary, and FSH secretion rises. FSH stimulates several follicles in an ovary to develop. A follicle is a fluid-filled sac in which an oocyte matures, surrounded by follicle cells. Usually only one follicle continues to grow to maturity.

The follicle cells secrete oestradiol, so oestradiol concentration rises as the follicle grows. Oestradiol has two effects. It stimulates repair and thickening of the endometrium after menstruation. At first it also inhibits FSH secretion, which is negative feedback: the product of the follicle reduces the hormone that stimulated it, so that no more follicles start to develop.

Ovulation (around day 14)

When oestradiol concentration reaches a high level for about two days, its effect on the pituitary reverses. High oestradiol stimulates the pituitary to release a large surge of LH (and a smaller rise in FSH). This is positive feedback, because a rise in oestradiol causes a rise in LH, which leads to still more oestradiol from the maturing follicle. The LH surge causes the mature follicle to complete its development and burst, releasing the egg from the ovary into the oviduct. This is ovulation.

The luteal phase (days 15–28)

After ovulation, LH stimulates the remaining follicle cells to develop into the corpus luteum ("yellow body"). The corpus luteum secretes progesterone and some oestradiol. Progesterone maintains the thickened endometrium and makes it ready to receive an embryo. Progesterone and oestradiol together inhibit FSH and LH secretion by negative feedback, so no new follicles develop while the endometrium is prepared for a possible pregnancy.

If the egg is not fertilised, the falling LH concentration means the corpus luteum is no longer stimulated. It degenerates after about 10–14 days, and progesterone and oestradiol levels fall. Without progesterone the endometrium can no longer be maintained, so it breaks down and is shed: menstruation begins, and the next cycle starts. The fall in progesterone and oestradiol also removes their inhibition of the pituitary, so FSH rises again.

The graph of the menstrual cycle shows all four hormones and both cycles on one time axis. Reading it from top to bottom gives the chain of causes: pituitary hormones control events in the ovary, the ovary secretes oestradiol and progesterone, and these hormones control the endometrium and feed back to the pituitary.

Longer questions on the menstrual cycle ask for the whole chain of hormonal events in time order. A clear answer names the gland that secretes each hormone, the target of the hormone and its effect, and states which steps are positive and which are negative feedback.

Fertilisation in humans

During intercourse, several hundred million sperm are released into the vagina. They swim through the cervix and uterus into the oviducts, and only a few hundred reach the egg. Fertilisation usually takes place in the upper part of the oviduct, within about a day of ovulation. The released egg is surrounded by a layer of follicle cells and a jelly-like glycoprotein coat called the zona pellucida, which a sperm must cross before it reaches the egg itself.

From fusion of membranes to the first division

Fertilisation in humans follows a fixed sequence of events:

1. A sperm passes through the follicle cells and the zona pellucida and reaches the egg.

2. The plasma membrane of the sperm fuses with the plasma membrane of the egg.

3. The sperm nucleus enters the cytoplasm of the egg.

4. The tail and mitochondria of the sperm are destroyed inside the egg. As a result, mitochondria (and mitochondrial DNA) are inherited only from the mother.

5. The entry of the sperm triggers the egg to complete the second division of meiosis, so the egg nucleus becomes haploid.

6. The sperm and egg nuclei do not fuse. Instead, both nuclear membranes break down, so the 23 condensed chromosomes from the sperm and the 23 from the egg are free in the cytoplasm.

7. All 46 chromosomes attach to one shared spindle and take part in a joint mitosis, which produces a two-cell embryo with a diploid nucleus in each cell.

The diagram of the stages of fertilisation shows that the maternal and paternal chromosomes first come together on the spindle of the first mitosis. The first nuclei that contain both sets of chromosomes are therefore the two diploid nuclei of the two-cell embryo.

Hormones in in vitro fertilisation (IVF)

In vitro fertilisation (IVF) is a treatment for infertility in which eggs are fertilised outside the body ("in vitro" means "in glass") and the resulting embryos are placed in the uterus. It is used when, for example, the oviducts are blocked, sperm counts are low or the cause of infertility is unknown. The first baby conceived by IVF, Louise Brown, was born in Oldham, England, on 25 July 1978 after the work of Robert Edwards and Patrick Steptoe. Edwards received the Nobel Prize in Physiology or Medicine in 2010, and by 2018 more than 8 million babies had been born worldwide through IVF and related techniques.

Down-regulation: suspending the natural cycle

IVF depends on the precise use of the same hormones that control the menstrual cycle. The first stage stops the woman's own cycle so that the clinic, rather than the pituitary, controls when eggs mature. For about two weeks the woman takes a drug that suspends the normal secretion of FSH and LH, usually by daily injection or nasal spray. With no FSH or LH from the pituitary, follicles stop developing and there is no risk of the eggs being released by a natural LH surge before they can be collected.

Superovulation: stimulating many follicles

Next, the woman is given injections of FSH (often with some LH activity) every day for about 10–12 days. These doses are much higher than the body would produce, so many follicles develop at once instead of one. This is superovulation. Its purpose is to collect several eggs in one treatment cycle, which increases the chance that at least one embryo will develop.

Ultrasound scans and blood oestradiol levels are used to check how the follicles are growing. When the follicles are mature, an injection of hCG (human chorionic gonadotropin), which acts like LH, is given. It causes the final maturation of the eggs, which are collected about 36 hours later, just before they would otherwise be released.

Collection, fertilisation and transfer

1. Eggs are collected from the follicles with a fine needle guided by ultrasound, shortly before ovulation would occur.

2. Each egg is mixed with sperm in a dish, or a single sperm is injected into each egg (intracytoplasmic sperm injection, ICSI) when sperm are few or have low motility.

3. The fertilised eggs are cultured for two to five days and checked for normal development.

4. One or two embryos are transferred to the uterus through the cervix with a thin tube; spare embryos can be frozen for later use.

5. Progesterone is given, usually as a vaginal gel or by injection, to help the endometrium stay thick enough for implantation.

Sexual reproduction in flowering plants

Flowering plants (angiosperms) reproduce sexually, and the flower is the organ that carries out every stage, from making gametes to forming seeds. Many plants can also reproduce asexually, but the flower is always a structure for sexual reproduction.

Where the gametes are made

The male gametes are produced inside pollen grains, which form in the anthers. Each pollen grain is a tiny structure with a tough outer wall that protects the male gametes while they are carried to another flower. The female gametes are produced inside ovules, which develop in the ovary. Each ovule contains one egg cell (the female gamete) surrounded by protective layers called integuments, with a small opening, the micropyle, at one end.

Pollination

Pollination is the transfer of pollen from an anther to a stigma. Because the male gametes cannot swim, they rely on an external agent to carry them. Animals such as bees, butterflies, moths, birds and bats carry pollen in insect-pollinated (and animal-pollinated) plants, and the wind carries pollen in wind-pollinated plants such as grasses. Pollination only brings the pollen grain to the stigma; the gametes have not yet met, so pollination is a separate step that comes before fertilisation.

Growth of the pollen tube and fertilisation

A pollen grain that lands on a compatible stigma absorbs water and sugars from the sticky surface and germinates. A pollen tube grows out of the grain, down through the tissue of the style and into the ovary, digesting a path with enzymes it secretes. The male gametes travel down inside the tube. The tube enters an ovule through the micropyle and releases the male gametes. One male gamete fuses with the egg cell, which is fertilisation, and the resulting zygote divides by mitosis to form the embryo of the seed.

In flowering plants the second male gamete fuses with two other nuclei in the ovule to form a food-storing tissue called endosperm, so the process is called double fertilisation. After fertilisation, each ovule develops into a seed, and the ovary wall develops into a fruit that encloses the seeds.

Hermaphrodite flowers still reproduce sexually

Most flowering plants have hermaphrodite flowers, which contain both male parts (stamens) and female parts (carpels). Even when pollen from a flower lands on the stigma of the same flower, the process is still sexual reproduction, because haploid gametes produced by meiosis fuse to form a zygote. The offspring are not clones of the parent, since meiosis shuffles the parent's alleles into many different combinations in its gametes.

Structure of an insect-pollinated flower

Insect-pollinated flowers are adapted to attract insects and to make sure that pollen is picked up and delivered on each visit. The structures are arranged in rings on the receptacle at the top of the flower stalk: sepals on the outside, then petals, then stamens, with one or more carpels in the centre. A half-flower drawing cut vertically through the middle shows all of them.

The structure of the flower fits its function. An insect landing on the petals and pushing towards the nectaries at the base rubs against the anthers and picks up pollen on its body. When it visits the next flower of the same species, the sticky stigma collects some of that pollen. Wind-pollinated flowers, by contrast, are usually small and green with no nectaries, and have large feathery stigmas and anthers that hang outside the flower in the wind.

Methods that promote cross-pollination

Pollination can happen in two ways. In self-pollination, pollen from an anther lands on a stigma of the same flower or another flower on the same plant. In cross-pollination, pollen is carried from the anther of one plant to the stigma of a different plant of the same species. Cross-pollination brings together alleles from two different parents, so it produces more genetic variation in the offspring.

Many plant species have features that make self-pollination less likely and cross-pollination more likely:

• Different maturation times. The anthers and stigma of one flower are ready at different times. In rosebay willowherb (Chamaenerion angustifolium) the anthers release their pollen before the stigma of the same flower opens and becomes receptive, so the stigma usually receives pollen from older flowers on other plants.

• Separate male and female flowers on the same plant. Hazel (Corylus avellana) has male catkins that hang in the wind and release pollen, and small separate female flowers with red stigmas on the same tree. Wind can still carry pollen within one tree, but much of it reaches other trees.

• Separate male and female plants. In species such as holly (Ilex aquifolium) and the date palm (Phoenix dactylifera), each plant has only male or only female flowers, so self-pollination is impossible.

Whichever method a plant uses, the pollen still has to be carried between plants by an agent: by animals in animal-pollinated species, or by the wind. This dependence on pollinators is an example of interaction and interdependence between species, since many flowers and their insect visitors depend on each other.

Self-incompatibility increases genetic variation

Self-pollination leads to inbreeding, the breeding of closely related individuals. Inbreeding increases the proportion of homozygous genotypes in the offspring, so harmful recessive alleles are more often expressed and genetic diversity falls. Inbred plants often grow less vigorously and produce fewer seeds, an effect called inbreeding depression.

Many flowering plants have a genetic mechanism that stops self-fertilisation even when their own pollen reaches the stigma. In self-incompatibility, the plant recognises pollen that carries the same allele of a self-incompatibility gene as itself and rejects it. The gene is called the S-gene (for "self-sterility"), and the population usually contains many different S-alleles.

How the S-alleles work

In cabbages and their relatives (Brassica oleracea and Brassica rapa), a single S-locus with many alleles controls self-incompatibility. The pollen grain carries a protein coded for by the S-alleles of its parent plant, and the stigma surface carries a receptor protein coded for by the same locus. If the pollen protein matches the stigma receptor, the stigma cells block the pollen from absorbing water, so the pollen grain does not germinate. Pollen from a plant with different S-alleles is not recognised and can germinate and fertilise the ovules.

In other families, such as the rose family (which includes apples and cherries), the pollen grain germinates but the style destroys the growing pollen tube if its S-allele matches one of the style's own. In both systems, the result is that male and female gametes that fuse during fertilisation come from genetically different plants. Apple growers therefore plant at least two compatible varieties in an orchard, so that each can pollinate the other.

Seed dispersal and germination

After fertilisation, each ovule develops into a seed. A seed contains an embryo plant (with an embryonic root, the radicle, and an embryonic shoot, the plumule), a food store, and a tough protective seed coat called the testa. In beans and peas the food is stored in two large seed leaves, the cotyledons; in cereals such as wheat and maize it is stored in a separate tissue, the endosperm.

Seed dispersal

Seed dispersal is the spread of seeds away from the parent plant. It reduces competition between the young plants and their parent (and each other) for light, water and mineral ions, and allows the species to colonise new areas. Plants use several methods:

• Wind: the fruits of the dandelion (Taraxacum officinale) have a parachute of fine hairs, and sycamore fruits have wings that make them spin and drift.

• Animals eating fleshy fruits: birds eat blackberries, and the seeds pass through the gut unharmed and are deposited in droppings.

• Animals carrying hooked fruits: the fruits of burdock (Arctium) have hooks that catch in fur.

• Water: the fibrous fruits of the coconut palm float and can be carried across oceans.

• Explosive release: the pods of Himalayan balsam (Impatiens glandulifera) burst when touched and fling seeds several metres.

Pollination, fertilisation and seed dispersal are separate events that happen in a fixed order: pollen moves to the stigma, then gametes fuse inside the ovule, then the finished seeds move away from the parent.

Germination

Germination is the start of growth of the embryo in a seed. Many seeds are dormant when they are dispersed: their metabolism is very slow and they do not grow, even in good conditions, until dormancy has been broken (for example by a period of cold). A dormant seed survives unfavourable seasons because it contains very little water and its embryo uses its food store extremely slowly.

Germination needs three external conditions:

• Water, absorbed through the micropyle and testa. Water rehydrates the cells, activates enzymes and allows the transport of food reserves to the growing embryo.

• Oxygen, for aerobic cell respiration, which supplies the ATP needed for growth.

• A suitable temperature, because the enzymes involved have an optimum temperature; most seeds of temperate plants germinate well at about 15–25 °C.

Mobilisation of food reserves

The embryo cannot photosynthesise until its first leaves reach the light, so it depends entirely on the food store. When the seed absorbs water, the embryo secretes the plant hormone gibberellin. Gibberellin stimulates the production of hydrolytic enzymes that break down the stored food into small soluble molecules that can be transported to the growing regions:

• amylase hydrolyses starch to maltose, which is then converted to glucose for respiration and to sucrose for transport

• proteases hydrolyse stored proteins to amino acids, used to make new proteins

• lipases hydrolyse stored lipids (in oily seeds such as sunflower) to fatty acids and glycerol

The radicle emerges first and grows downwards, anchoring the seedling and absorbing water. The plumule then grows upwards. Once the first leaves open and begin to photosynthesise, the seedling no longer depends on the food store.

Case study: a date palm grown from a 2,000-year-old seed

The length of time a seed can survive shows how effectively a dormant embryo and its food store are protected. The most famous example is a Judean date palm (Phoenix dactylifera) known as Methuselah. The Judean date was once an important crop in the region around the Dead Sea but it died out many centuries ago, and no living trees of this type remained.

In the 1960s, archaeologists excavating the ancient fortress of Masada in Israel recovered a store of date seeds. They were kept dry for about 40 years. In 2005, three of the seeds were treated with water, fertiliser and a hormone solution and planted by the plant scientist Elaine Solowey, in a project led by the physician Sarah Sallon. One germinated and grew into a healthy palm. Radiocarbon dating of fragments of the seed coat left attached to the seedling showed that the seed was about 2,000 years old, beating the previous record for the germination of an old seed, a lotus (Nelumbo nucifera) seed from China about 1,300 years old.

The team later tried the method on more ancient seeds. Of 32 date seeds from Masada, Qumran and Wadi Makukh, 6 germinated and grew into young trees, and radiocarbon dating placed them between about the 4th century BCE and the 2nd century CE.

Sources: Sallon et al., Science 320:1464, 2008; Sallon et al., Science Advances 6:eaax0384, 2020.

The case study connects several ideas. The seed is the product of sexual reproduction: it formed from an ovule fertilised by pollen carried from a male palm, since date palms have separate male and female trees. Its long survival depended on dormancy, a dry embryo with almost no metabolism, protected by the testa. When water was supplied, the embryo mobilised its stored food and grew. Seeds therefore disperse a species through time as well as through space. Methuselah itself turned out to be a male tree, and its pollen has since been used to pollinate a female tree grown from one of the other ancient seeds.

Puberty: GnRH and the steroid sex hormones (HL only)

Puberty is the stage of development in which the body becomes sexually mature and able to reproduce. It usually begins between about 8 and 13 years of age in girls and between about 9 and 14 in boys. The changes are caused by a rise in the concentration of the steroid sex hormones, and that rise is started by the brain.

A three-step hormone cascade

Puberty is controlled by a cascade of three hormones, each stimulating the secretion of the next:

1. During late childhood the hypothalamus increases its secretion of gonadotropin-releasing hormone (GnRH), released in pulses into the blood vessels that lead to the anterior pituitary.

2. GnRH stimulates the anterior pituitary to increase its release of LH and FSH (the gonadotropins, so called because they act on the gonads).

3. LH and FSH stimulate the gonads. The ovaries increase their production of oestradiol and progesterone, and the testes increase their production of testosterone. These steroid hormones cause the changes of puberty.

Before puberty, the gonads are able to respond to LH and FSH, but the small amounts of GnRH released keep the gonadotropins low. Puberty therefore begins in the brain, when the hypothalamus increases GnRH secretion, and the gonads respond to the rising LH and FSH.

Spermatogenesis and oogenesis (HL only)

The production of gametes is called gametogenesis. In males it is spermatogenesis and takes place in the seminiferous tubules of the testes; in females it is oogenesis and takes place in the ovaries. Both follow the same four stages: mitosis, cell growth, the two divisions of meiosis, and differentiation.

Spermatogenesis

1. Mitosis. Diploid germ cells called spermatogonia, in the wall of each seminiferous tubule, divide repeatedly by mitosis. Some daughter cells remain as spermatogonia, so the supply never runs out.

2. Cell growth. Some spermatogonia grow larger to become primary spermatocytes (2n).

3. Meiosis I. Each primary spermatocyte divides to form two haploid secondary spermatocytes.

4. Meiosis II. Each secondary spermatocyte divides to form two spermatids, giving four haploid spermatids from each primary spermatocyte.

5. Differentiation. Spermatids develop into sperm: they lose most of their cytoplasm, grow a flagellum, pack mitochondria into the midpiece and form an acrosome over the nucleus. Sertoli cells in the tubule wall nourish them as they develop.

Spermatogenesis is continuous from puberty onwards and takes about 64–74 days from spermatogonium to sperm. Because all four products of each meiosis become sperm, and millions of cells are dividing at once, a man produces millions of sperm every day.

Oogenesis

1. Mitosis. Before birth, diploid germ cells called oogonia in the fetal ovary divide by mitosis.

2. Cell growth. Oogonia grow into primary oocytes (2n), which start meiosis I and then stop at prophase I. Each becomes surrounded by follicle cells, forming a primary follicle. A girl is born with about a million or more primary oocytes, and no more are made.

3. Meiosis I. From puberty, during each menstrual cycle, one primary oocyte completes meiosis I just before ovulation. The division of the cytoplasm is very unequal: one large secondary oocyte (n) receives almost all the cytoplasm, and a tiny first polar body receives a set of chromosomes and very little else.

4. Meiosis II. The secondary oocyte starts meiosis II but stops at metaphase II, and it is in this state when it is released at ovulation. Meiosis II is completed only if a sperm enters, producing the ovum and a second polar body.

5. Differentiation. As the oocyte develops inside the follicle it grows large, builds up food reserves and forms cortical granules and the zona pellucida around itself.

The diagram of spermatogenesis and oogenesis shows why the gametes differ. In spermatogenesis the cytoplasm divides equally, and most of it is then discarded as sperm differentiate, so the sperm are small and numerous. In oogenesis the unequal divisions concentrate the cytoplasm, with its food reserves, mitochondria and ribosomes, in a single cell. A woman ovulates only around 400–500 eggs in her life, one in most cycles from puberty to the menopause.

From fertilisation to implantation (HL only)

Mechanisms that prevent polyspermy

Only one sperm must fertilise each egg. If two or more sperm nuclei entered, the zygote would have three or more sets of chromosomes and could not develop normally. Fertilisation by more than one sperm is called polyspermy, and two processes ensure that exactly one sperm enters.

The acrosome reaction allows one sperm through

The acrosome is a large vesicle in the head of the sperm, filled with hydrolytic enzymes. When a sperm binds to glycoproteins of the zona pellucida, the acrosome fuses with the plasma membrane of the sperm and releases its enzymes. This is the acrosome reaction. The enzymes digest a narrow path through the zona pellucida, and the beating flagellum pushes the sperm along it to the plasma membrane of the egg.

The cortical reaction blocks the others

Just inside the plasma membrane of the egg there are thousands of small vesicles called cortical granules. When the plasma membranes of the sperm and egg fuse, the cortical granules fuse with the egg membrane and release their contents into the gap between the membrane and the zona pellucida. This is the cortical reaction. The released enzymes alter the glycoproteins of the zona pellucida so that it hardens and no longer binds sperm, so no other sperm can pass through it.

Sea urchin eggs, which are fertilised in open water by huge numbers of sperm, have been the classic model for studying these blocks. In sea urchins a fast electrical block, a change in the membrane potential of the egg within seconds of fusion, comes before the slower cortical reaction.

Development of the blastocyst

The zygote divides by mitosis as it is carried down the oviduct towards the uterus, a journey of about three to four days. The early divisions produce a solid ball of small cells that stays inside the zona pellucida. By about day 5 after fertilisation a fluid-filled cavity has formed in the ball, which is now called a blastocyst.

The blastocyst has three parts, shown in the drawing of a blastocyst:

• Trophoblast: the outer layer of cells, which will invade the endometrium and form the embryo's part of the placenta.

• Inner cell mass: a group of cells on one side of the inside, which will develop into the embryo; these cells are pluripotent stem cells.

• Blastocoel: the fluid-filled cavity.

Implantation in the endometrium

At about day 5–6 the blastocyst escapes ("hatches") from the zona pellucida, and at about day 6–7 it attaches to the endometrium, which has been thickened and maintained by progesterone. The trophoblast cells grow finger-like projections into the endometrium and digest their way into it, so that the blastocyst becomes embedded in the lining of the uterus. This is implantation. Once implanted, the embryo can absorb nutrients and oxygen from the maternal tissue, and the trophoblast begins to secrete hCG.

Pregnancy testing with monoclonal antibodies (HL only)

Human chorionic gonadotropin (hCG) is a glycoprotein hormone secreted by the trophoblast of the embryo from about the time of implantation, and later by the placenta. hCG stimulates the corpus luteum to keep secreting progesterone, so the endometrium is maintained and menstruation does not happen. Without hCG, the corpus luteum would degenerate at the end of the cycle and the embryo would be lost with the endometrium.

Because hCG is made only by an embryo (or by some rare tumours), its presence in the blood or urine is a reliable sign of pregnancy. hCG concentration rises quickly in early pregnancy, roughly doubling every 2–3 days. Home pregnancy tests typically detect about 25 mIU/mL of hCG in urine, a level usually reached around the time of the first missed period.

Monoclonal antibodies

A monoclonal antibody is one type of antibody, all identical, produced by a clone of cells derived from a single B-lymphocyte. Every molecule binds to exactly the same site on its target antigen. Monoclonal antibodies are made by fusing a B-lymphocyte that produces the required antibody with a tumour cell, which gives a hybrid cell (a hybridoma) that divides indefinitely in culture. Antibodies that bind specifically to hCG are produced this way for pregnancy tests.

How a pregnancy test strip works

1. Urine is applied to the sample pad and soaks along the strip by capillary action.

2. The urine passes a region of mobile monoclonal antibodies against hCG, each attached to a coloured dye (or a coloured particle). If hCG is present, it binds to these antibodies.

3. At the test line, a second type of monoclonal antibody against hCG is fixed to the strip. It binds to a different site on the hCG molecule. Any hCG carrying a dyed antibody is held here, so a coloured line appears. Without hCG, the dyed antibodies pass straight over the test line.

4. At the control line, fixed antibodies bind to the mobile antibodies themselves, whether or not they carry hCG. A coloured control line shows that the urine has flowed along the strip and the antibodies are working.

5. Two lines therefore mean pregnant; one line (control only) means not pregnant; no control line means the test has failed.

Role of the placenta (HL only)

The placenta is a disc-shaped organ that forms from the trophoblast of the embryo together with tissue of the endometrium. It is connected to the fetus by the umbilical cord, which contains two umbilical arteries (carrying fetal blood to the placenta) and one umbilical vein (carrying blood back to the fetus). Its role is exchange: it supplies the fetus with everything it needs and removes its waste, while keeping the blood of the mother and the fetus separate.

A large surface area for exchange

The fetal side of the placenta is covered with thousands of finger-like placental villi, which project into spaces filled with maternal blood. Each villus contains fetal capillaries. The villi give the placenta a very large surface area for exchange, and the barrier between maternal and fetal blood is very thin, so substances cross it quickly. The diagram of a placental villus shows that fetal blood stays inside its capillaries while maternal blood flows around the outside of the villus.

The antibodies that cross the placenta give the newborn baby passive immunity for its first months, against the diseases the mother is immune to. Some harmful substances, such as alcohol, nicotine, some drugs and certain viruses, can also cross the placenta.

The placenta allows a longer development inside the uterus

The placenta allows the fetus to remain inside the uterus until a later stage of development than in mammals without one. A human fetus is born after about 38 weeks of development. In marsupials, which have only a short-lived simple placenta, the young are born at a very early stage and complete development in a pouch. A red kangaroo (Osphranter rufus) is born after about 33 days, when it is about 2 cm long, and then crawls into its mother's pouch to continue growing.

Hormonal control of pregnancy and childbirth (HL only)

Maintaining the pregnancy

Progesterone is the hormone that maintains a pregnancy. It keeps the endometrium thick and supplied with blood, and it inhibits contractions of the muscle of the uterus wall. It also inhibits FSH and LH, so no new menstrual cycle starts. The source of progesterone changes during pregnancy:

1. In the first weeks, hCG from the embryo keeps the corpus luteum alive, and the corpus luteum secretes progesterone (and oestradiol).

2. As the placenta grows, it starts to secrete progesterone and oestrogen itself. By about the end of the first three months (around weeks 8–12) the placenta produces enough progesterone to maintain the pregnancy.

3. hCG levels then fall, and the corpus luteum degenerates without any harm to the pregnancy.

The graph of hormone levels in pregnancy shows the hand-over: hCG is high while the corpus luteum is the main source of progesterone, and falls once the placenta has taken over.

Childbirth and positive feedback

Near the end of pregnancy the inhibiting effect of progesterone on the uterus falls, partly because progesterone secretion falls and partly because the uterus becomes less responsive to it. Rising oestrogen makes the muscle of the uterus more sensitive to oxytocin, a hormone secreted by the posterior pituitary. Childbirth then proceeds by positive feedback:

1. Oxytocin stimulates the muscle of the uterus wall to contract.

2. The contractions push the fetus against the cervix, which is stretched.

3. Stretch receptors in the cervix send nerve impulses to the hypothalamus.

4. The hypothalamus stimulates the posterior pituitary to secrete more oxytocin.

5. More oxytocin causes stronger, more frequent contractions, which stretch the cervix more, so the cycle intensifies.

The positive feedback continues until the baby is born and the cervix is no longer stretched. This shows a key difference from negative feedback: positive feedback amplifies a change and drives a process to completion, instead of returning a variable to a set point.

Hormone replacement therapy and coronary heart disease (HL only)

At the menopause, usually between the ages of about 45 and 55, the ovaries stop releasing eggs and secrete much less oestradiol and progesterone. The fall in these hormones can cause hot flushes, night sweats, sleep disturbance and a loss of bone density. Hormone replacement therapy (HRT) relieves these symptoms by giving oestrogen, usually combined with a progestogen (a synthetic progesterone) in women who still have a uterus.

What the early studies suggested

Before the menopause, women have a lower rate of coronary heart disease (CHD) than men of the same age, and the rate rises after the menopause. This suggested that oestrogen protects the arteries. Large observational (epidemiological) studies in the 1980s and 1990s, such as the Nurses' Health Study in the USA, followed thousands of women and found that those who chose to take HRT had a considerably lower rate of CHD than those who did not. On this evidence, many doctors began to recommend HRT partly to prevent heart disease.

What the randomised controlled trials showed

An observational study can show a correlation but cannot by itself establish causation. In a randomised controlled trial (RCT), participants are assigned at random to receive the treatment or a placebo, so the two groups are alike in every other way, on average. The Women's Health Initiative (WHI) trial in the USA randomly assigned 16,608 postmenopausal women aged 50–79 to combined oestrogen plus progestin or to a placebo. In 2002 the trial was stopped early, after an average of 5.2 years, because the risks of HRT outweighed its benefits.

Source: Writing Group for the Women's Health Initiative Investigators, JAMA 288:321, 2002.

A hazard ratio above 1 means the event was more frequent in the HRT group. The trial showed that combined HRT caused a small increase in the risk of CHD, the opposite of what the observational studies had suggested, although it reduced fractures and colorectal cancer.

Why the observational studies were misleading

The earlier correlation was real, but it was not caused by HRT. The women who chose to take HRT differed in other ways from those who did not: on average they had a higher socio-economic status, better access to health care, healthier diets and more exercise, and these factors themselves reduce the risk of CHD. Socio-economic status was a confounding variable, a factor linked to both the treatment and the outcome, which created a correlation between HRT and lower CHD without any cause-and-effect link. Randomisation removes this problem, because it spreads such factors evenly between the groups.

Exam practice

Reproduction is assessed in every part of the exam. Paper 1A multiple-choice questions often test the sources and effects of the menstrual-cycle hormones, the functions of the parts of a flower, and the order of events in fertilisation. Paper 1B and Paper 2 Section A use graphs of hormone levels, germination experiments and, at HL, data from clinical trials. Paper 2 also asks for annotated drawings of the reproductive systems and of a flower, and Section B often includes an extended response on the hormonal control of the menstrual cycle, IVF, or (HL) gametogenesis and pregnancy. The command terms most often used are annotate, outline, explain, compare and contrast, deduce and evaluate.

Flowering plants and humans meet the same needs of sexual reproduction with different structures. Anthers and testes both produce male gametes, each ovule and each ovarian follicle holds one female gamete, and the pollen tube and the sperm duct both carry male gametes towards the egg. These parallels are an example of unity and diversity in living organisms.

Self-check

• To do:

  I can compare sexual and asexual reproduction and give an advantage of each.

• To do:

  I can explain how meiosis and fertilisation produce new combinations of alleles.

• To do:

  I can draw and annotate the human male and female reproductive systems.

• To do:

  I can explain the roles of FSH, LH, oestradiol and progesterone in the menstrual cycle, including positive and negative feedback.

• To do:

  I can describe the events of fertilisation in humans and outline the hormones used in IVF.

• To do:

  I can draw and annotate an insect-pollinated flower and describe pollination, pollen-tube growth and fertilisation.

• To do:

  I can explain how cross-pollination and self-incompatibility increase genetic variation.

• To do:

  I can distinguish pollination, fertilisation and seed dispersal, and outline germination.

• To do:

  I can explain how GnRH starts puberty and compare spermatogenesis with oogenesis. (HL)

• To do:

  I can explain how the acrosome and cortical reactions prevent polyspermy, and draw a blastocyst. (HL)

• To do:

  I can explain how pregnancy tests, the placenta, progesterone and oxytocin support pregnancy and birth. (HL)

• To do:

  I can evaluate the evidence about HRT and coronary heart disease, distinguishing correlation from causation. (HL)

1. A

   Halves, breaks up; restores, new combinations

2. B

   Halves, keeps; restores, new combinations

3. C

   Keeps diploid, breaks up; halves, new combinations

4. D

   Halves, breaks up; restores, keeps combinations