Gametes, fertilisation and early development

Spermatogenesis and oogenesis

Both gametes are produced by meiosis. Independent assortment, crossing over and the variation they generate are covered in meiosis and the sources of genetic variation. What matters here is that the same division follows two different timetables in the two sexes and produces two structurally different cells.

Spermatogenesis happens in the seminiferous tubules of the testis. Diploid cells in the germinal epithelium lining each tubule divide by mitosis, and some of the daughter cells grow into primary spermatocytes. Each of those completes the first meiotic division into two haploid secondary spermatocytes, and each of those completes the second into two spermatids, so one primary spermatocyte yields four. The spermatids then mature into spermatozoa, attached to Sertoli cells that supply them with nutrients. The whole sequence runs continuously from puberty, and a healthy adult produces of the order of a hundred million sperm a day.

Oogenesis starts before birth and then waits. Diploid cells in the fetal ovary divide by mitosis, begin the first meiotic division, and stop part way through it. Every primary oocyte a person will ever have is present at birth, arrested, each one inside a follicle. From puberty a few follicles develop in each cycle, and usually one primary oocyte completes the first division. That division is unequal: nearly all the cytoplasm passes to one daughter, the secondary oocyte, and the other becomes a small polar body that takes no further part.

The second division is also arrested. The cell released at ovulation has begun the second meiotic division and stopped part way through it, completing only if a sperm fuses with it, which produces the mature ovum and a second polar body. Specifications differ in how closely they distinguish the secondary oocyte from the ovum, so use the term your own specification uses.

Gamete structure and function

Each gamete illustrates structure fitted to function. Name each structure and give the function it performs.

Describe the drawing

An egg drawn large at the top, surrounded by follicle cells, with a thick zona pellucida outside its cell surface membrane, cortical granules lying just inside that membrane, a haploid nucleus at the centre and cytoplasm holding organelles and maternal RNAs. Below it a sperm drawn much enlarged, with the acrosome full of enzymes at the leading tip, the haploid nucleus behind it, a mid-piece packed with mitochondria, and a long tail. At the bottom both are drawn again at one scale, where the egg is a circle twice as wide as the whole sperm is long.

The sperm is adapted for motility and for penetrating the layers around the egg. The acrosome is a vesicle over the front of the head holding hydrolytic enzymes, and those enzymes are what makes a path through the layers around the egg. Behind it the haploid nucleus carries 23 chromosomes in a human, tightly condensed, with very little cytoplasm around it, which keeps the cell small. The mid-piece is packed with mitochondria, which release the ATP that the tail uses to beat. The tail is the only means of movement the cell has.

The egg supplies the cytoplasm of the zygote and determines which sperm can bind. It has a large cytoplasmic volume containing organelles, maternal RNAs and nutrients that support the first stages of development. Its haploid nucleus supplies the other 23 chromosomes, and the mitochondria in that cytoplasm are, in effect, the only ones the embryo keeps: any paternal mitochondria that enter are normally recognised and destroyed, which is why mitochondrial DNA is inherited from the mother alone. Around the outside of the cell surface membrane is the zona pellucida, a coat of glycoproteins carrying the receptors a sperm has to bind to, and outside that a layer of follicle cells from the follicle it was released from. Just inside the membrane lie the cortical granules, whose contents are released only at fusion.

Acrosome

A vesicle at the front of a sperm head containing hydrolytic enzymes, which are released to digest a path through the layers around the egg.

Zona pellucida

The glycoprotein coat outside the egg's cell surface membrane, carrying the receptors a sperm binds to.

Cortical granules

Vesicles lying just inside the egg's cell surface membrane, whose contents are released at fertilisation and change the zona pellucida.

Polyspermy

Fusion of more than one sperm with a single egg, which gives a cell with too many chromosome sets to develop.

The acrosome reaction

The sequence from arrival to entry has four steps, and the order is required. Learn it as a chain in which each step causes the next.

Describe the drawing

Four rows, each showing the edge of the egg as a zona pellucida, a cell surface membrane and a sliver of cytoplasm. In the first a sperm approaches the zona pellucida, and binding to it makes the acrosome release its enzymes by exocytosis. In the second those enzymes digest a path through the zona pellucida. In the third the two membranes fuse and a single sperm nucleus crosses into the egg, where the sperm's mitochondria are later destroyed. In the fourth cortical granules empty outwards, the zona thickens, and a second sperm is turned away.

First the sperm works its way through the layer of follicle cells and binds to a receptor on the zona pellucida. The binding is between complementary molecules, so it is specific: this is one of the reasons fertilisation between species usually fails.

That binding triggers the acrosome reaction. The membrane around the acrosome fuses with the sperm's own cell surface membrane, and the hydrolytic enzymes are released to the outside by exocytosis. The acrosome reaction is the release of the enzymes, not the digestion that follows.

The enzymes then digest a path through the zona pellucida, and the sperm swims down it until its own cell surface membrane meets the egg's. The two membranes fuse, and the sperm nucleus passes into the cytoplasm of the egg. In a mammal the mid-piece and tail are usually taken in as well, but the egg recognises the sperm's mitochondria and destroys them, which is why paternal mitochondrial DNA is not passed on.

The cortical reaction and the prevention of polyspermy

Fusion of the membranes causes a sharp rise in the concentration of calcium ions in the egg's cytoplasm, and that rise sets off the cortical reaction. The cortical granules fuse with the cell surface membrane and empty their contents by exocytosis into the space between that membrane and the zona pellucida.

Those contents modify the zona pellucida. The receptors a sperm binds to are altered so that no further sperm can attach, and the coat hardens, so any sperm already within it cannot proceed. State the mechanism as a chemical modification of the zona pellucida rather than as physical exclusion of further sperm.

Each gamete contributes one set of chromosomes, 23 in a human, and the zygote requires exactly two sets. If a second sperm fused, the cell would contain 69 chromosomes in three sets. The reason a triploid cell fails is not an inability to divide: every chromosome is replicated in S phase before mitosis, so a cell with three sets can divide mitotically and produce daughters that still have three sets.

A triploid embryo fails because of gene dosage. Every gene is present in three copies rather than two, so the balance of gene products is altered throughout, and the effect is greatest on the imprinted genes whose expression depends on the number of copies inherited from each parent. The result is severe abnormality of the embryo and the placenta, and development fails early.

Two events remain before fertilisation is complete. The arrival of the sperm nucleus triggers the egg to complete meiosis II, releasing the second polar body. The two haploid nuclei then come together and fuse, and 23 plus 23 gives the diploid 46 of a human zygote. Only at that fusion is fertilisation complete: a sperm inside the egg with the nuclei still separate is not yet a zygote.

Cleavage, the blastocyst and implantation

Fertilisation happens in the oviduct, most often in the wider part nearest the ovary, and the zygote begins dividing while it is still travelling. The first division comes about a day after fertilisation, and the divisions that follow are given their own name: cleavage.

Describe the drawing

Five stages in a row, each drawn inside a circle of the same size: one cell labelled zygote, then two, then four, then eight, then about a hundred forming a blastocyst with a hollow cavity, a rim of cells around it and an inner cell mass picked out at one side. Dashed lines across the top and bottom of every stage show that the total size does not change while the cells inside get smaller and more numerous.

Cleavage differs from ordinary mitosis in the absence of a substantial growth phase between divisions. A cell divides and the two daughters divide again without first returning to the size of the parent. The number of cells rises through two, four, eight and sixteen, each cell smaller than the last, while the whole structure remains about the size of the original egg.

At about day four the embryo is a solid ball of cells called a morula. By about day five a fluid-filled cavity has opened inside it and it is a blastocyst: an outer layer of cells that will go on to form part of the placenta, the cavity, and a cluster at one side called the inner cell mass from which the embryo itself develops. That cluster is the source of pluripotent embryonic stem cells. Prerequisite: stem cells and cell potency.

The blastocyst then escapes from the zona pellucida that has surrounded it all this time, and implants in the endometrium, the lining of the uterus, about six or seven days after fertilisation. State both locations: fertilisation in the oviduct, implantation in the uterus. An embryo that implants in the oviduct instead is an ectopic pregnancy, which cannot continue and is dangerous to the mother.