Gametes and fertilisation: from two cells to a blastocyst

Two cells, two very different production lines

Both gametes are made by meiosis, and meiosis has a lesson of its own: independent assortment, crossing over and the variation they produce belong there rather than here. What belongs here is that the same division is run on two quite different timetables and produces two quite 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 deliberately unequal: nearly all the cytoplasm goes to one daughter, the secondary oocyte, and the other becomes a small polar body that takes no further part.

The second division is stranger still. The cell released at ovulation has begun the second meiotic division and stopped in the middle of it, and it finishes only if a sperm fuses with it, producing the mature ovum and a second polar body. Textbooks and specifications vary in how carefully they distinguish the secondary oocyte from the ovum, so check which word your own course uses; the biology underneath is the same either way.

Built for the job

Each gamete is a standing example of structure fitted to function, which is why examiners keep returning to it. Take each structure and give it a job, because that pairing is what the mark scheme is written as.

The sperm is built to travel and to get through. 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 is built to supply and to be selective. Its large volume of cytoplasm holds lipid droplets and glycogen, a store the embryo lives on until it implants. 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 sit the cortical granules, which have nothing to do until the moment of fusion and then have everything to do.

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 what is marked. Learn it as a chain in which each step causes the next.

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. Note what the phrase names: the 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. The tail and the mid-piece are mostly left behind or broken down, and any paternal mitochondria that do get in are normally eliminated by the egg, which between them is why paternal mitochondrial DNA is not passed on.

The cortical reaction, and why polyspermy has to be prevented

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.

What those contents do is change the zona pellucida. The receptors a sperm binds to are altered so that no further sperm can attach, and the coat itself hardens, so any sperm already inside it can go no further. The block is therefore chemical rather than physical in the first instance, and it is worth saying so in an answer: the granules do not push sperm away, they modify the layer the sperm needs.

Now the reason it matters. Each gamete brings one set of chromosomes, 23 in a human, and the zygote needs exactly two sets. If a second sperm fused, the cell would hold 69 chromosomes in three sets. Be careful with the reason this fails, because the obvious one is wrong: mitosis copies every chromosome before dividing, so a cell with three sets can divide mitotically and produce daughters that still have three sets.

What a triploid embryo cannot survive is the dose. Every gene is present in three copies rather than two, so the balance of gene products is wrong throughout, and it falls hardest on the imprinted genes whose expression depends on how many copies came from each parent. The result is severe abnormality of the embryo and the placenta, and development fails early. Polyspermy is not a variation on fertilisation, it is a failure of it.

Two cells still have to finish what they were doing. 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.

What makes cleavage different from ordinary mitosis is what is missing between the divisions. There is no growth phase worth the name, so a cell divides, and the two daughters divide again without first getting back to the size of the parent. Two cells, four, eight, sixteen: the number rises and each cell is smaller than the last, while the ball as a whole stays 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, which is where this lesson meets the one before it.

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. Say both places when a question asks: 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, and it is the clearest evidence that the two locations are not interchangeable.