Human Reproduction

The male reproductive system is located in the pelvic region and is built from four kinds of parts: a pair of testes, a set of accessory ducts, a set of accessory glands, and the external genitalia. It helps to keep those four groups separate in your head, because most of the naming work in this topic is really about sorting a structure into the right group.

The testes are the primary sex organs. They sit outside the abdominal cavity in a pouch of skin called the scrotum, and this position is not an accident. The scrotum keeps the temperature of the testes about 2 to 2.5 degrees Celsius lower than the normal internal body temperature, and that lower temperature is necessary for sperm production. If the testes stay inside the warm abdomen, spermatogenesis does not proceed normally. Each adult testis is oval, roughly 4 to 5 centimetres long and 2 to 3 centimetres wide, and is enclosed in a dense covering. Inside, the testis is divided into about 250 compartments called testicular lobules, and each lobule contains one to three highly coiled seminiferous tubules. The sperms are made inside these tubules.

Look inside a single seminiferous tubule and you find its inner lining made of two very different cell types. The first are the male germ cells, the spermatogonia, which sit against the wall and divide to eventually give sperms. The second are the Sertoli cells, tall cells that stretch across the thickness of the lining; their job is to nourish and support the developing germ cells. Now step outside the tubules. The spaces between neighbouring seminiferous tubules are called interstitial spaces, and they contain small blood vessels along with the interstitial cells, also called Leydig cells. Leydig cells synthesise and secrete the testicular hormones, the androgens. Immunologically competent cells are also present here. Hold on to this inside-outside split: germ cells and Sertoli cells are inside the tubule, Leydig cells are outside it in the interstitial space.

The accessory ducts form one continuous path. Sperms leave the seminiferous tubules and pass into the rete testis, then into the vasa efferentia, which carry them out of the testis into the epididymis. The epididymis is a long coiled duct lying along the posterior surface of each testis. It leads into the vas deferens, which ascends into the abdomen and loops over the urinary bladder. There, the vas deferens receives a duct from the seminal vesicle, and the two together open into the urethra as the ejaculatory duct. The urethra begins at the urinary bladder and runs through the penis to open at the urethral meatus. Together these ducts store the sperms and transport them out of the body. The penis is the male external genitalia; its enlarged end is called the glans penis and is covered by a loose fold of skin, the foreskin.

Three sets of accessory glands add fluid to the sperms: a pair of seminal vesicles, a single prostate, and a pair of bulbourethral glands. Their combined secretions form the seminal plasma, which is rich in fructose, calcium and certain enzymes. The fructose matters because it is the sugar the sperms use as fuel. Semen is simply sperms suspended in this seminal plasma. The secretion of the bulbourethral glands is lubricating. Notice the counts as you learn the names: seminal vesicles paired, bulbourethral glands paired, prostate single.

The female reproductive system lies in the pelvic region and consists of a pair of ovaries, a pair of oviducts, the uterus, the cervix, the vagina and the external genitalia. The mammary glands are counted with this system too, because structurally and functionally the whole set works together to support the release of an ovum, fertilisation, pregnancy, birth and the care of the newborn.

The ovaries are the primary female sex organs. They produce the female gamete, the ovum, and they also secrete several steroid hormones, the ovarian hormones. One ovary sits on each side of the lower abdomen, each about 2 to 4 centimetres long, held to the pelvic wall and to the uterus by ligaments. An ovary is covered by a thin epithelium, and inside that lies the ovarian stroma. The stroma has two zones: a peripheral cortex and an inner medulla. The follicles that contain the developing gametes lie in the cortex, which is why the cortex is the part that changes visibly through a cycle.

The oviducts, uterus and vagina are the female accessory ducts. Each oviduct, also called a fallopian tube, is about 10 to 12 centimetres long and runs from near the ovary to the uterus. Trace it from the ovary inwards, because that is the direction an ovum travels. The end closest to the ovary is a funnel-shaped opening, the infundibulum. Its edge carries finger-like projections called fimbriae, and these help collect the ovum after it is released from the ovary. The infundibulum leads into a wider part of the tube called the ampulla. The last part, nearest the uterus, is the isthmus, which has a narrow lumen and joins the uterus. So the order along the tube is infundibulum, ampulla, isthmus, uterus.

The uterus, also called the womb, is a single pear-shaped organ held by ligaments to the pelvic wall. It opens into the vagina through a narrow neck called the cervix. The cavity of the cervix is the cervical canal, and the cervical canal together with the vagina forms the birth canal. The uterine wall has three layers. The outermost is the perimetrium, a thin membranous covering. The middle layer is the myometrium, a thick layer of smooth muscle. The innermost is the endometrium, a glandular layer that lines the uterine cavity. These two inner layers have completely different jobs and must not be confused. The endometrium is the layer that undergoes cyclical changes through the menstrual cycle, thickening and then breaking down. The myometrium is the muscle that contracts strongly during the delivery of the baby. The female external genitalia include the mons pubis, the labia majora, the labia minora, the hymen and the clitoris.

The mammary glands are paired and contain glandular tissue along with a variable amount of fat. The glandular tissue of each breast is divided into 15 to 20 mammary lobes, and each lobe contains clusters of cells called alveoli. The cells of the alveoli secrete milk, and the milk is stored in the cavities of the alveoli. From there the path out is a chain worth memorising in order: alveoli open into mammary tubules, the tubules of a lobe join to form a mammary duct, several mammary ducts join to form a wider mammary ampulla, and the ampulla connects to a lactiferous duct through which the milk is drawn out. Note that the word ampulla is used twice in this chapter, once for a widened part of the oviduct and once for a widened part of the milk-carrying passage; read the surrounding words before answering.

Gametogenesis is the making of gametes from germ cells. In the male it is called spermatogenesis and in the female, oogenesis. Both involve one round of meiosis, so both end with haploid cells carrying 23 chromosomes, but almost everything else about them differs. Follow each sequence as a list of named cells, and attach a chromosome number to each name as you go.

Spermatogenesis begins at puberty and then continues. The spermatogonia lying on the inner wall of the seminiferous tubules multiply by mitosis and increase in number. Each spermatogonium is diploid and contains 46 chromosomes. Some of these spermatogonia, now called primary spermatocytes, periodically undergo meiosis. A primary spermatocyte is still diploid with 46 chromosomes. It completes the first meiotic division, which is the reduction division, and gives two equal haploid cells called secondary spermatocytes, each with 23 chromosomes. Each secondary spermatocyte then undergoes the second meiotic division, so one primary spermatocyte finally yields four equal haploid spermatids, each with 23 chromosomes. Notice the two words for the two later steps. Spermiogenesis is the transformation of a spermatid into a spermatozoon, that is, the reshaping of a round cell into a motile sperm. Spermiation is the release of the formed sperms from the seminiferous tubules; before that release, the sperm heads remain embedded in the Sertoli cells. The two words look alike, so fix the difference now: spermiogenesis is a change of shape, spermiation is a release.

The hormonal control runs from the brain downwards. At puberty the hypothalamus increases its secretion of gonadotropin releasing hormone, GnRH. GnRH acts on the anterior pituitary and makes it secrete two gonadotropins, luteinising hormone (LH) and follicle stimulating hormone (FSH). LH acts on the Leydig cells and stimulates the synthesis and secretion of androgens, and the androgens then stimulate spermatogenesis. FSH acts on the Sertoli cells and stimulates the secretion of factors that help spermiogenesis. So both gonadotropins come from the anterior pituitary, but they act on different target cells in the testis: LH on Leydig cells, FSH on Sertoli cells.

A mature human sperm is a microscopic cell with four regions: a head, a neck, a middle piece and a tail, and a plasma membrane covers the whole of it. The head contains an elongated haploid nucleus, and the front part of the head is covered by a cap-like structure, the acrosome. The acrosome is filled with enzymes that help the sperm fertilise the ovum. The middle piece contains numerous mitochondria, and these supply the energy for the beating of the tail, which gives the sperm its motility. A human male releases about 200 to 300 million sperms during a single ejaculation; for normal fertility, at least 60 per cent of them must have a normal shape and size and at least 40 per cent must show vigorous motility.

Oogenesis is different from the first step onwards, because it starts before birth. During embryonic development, a couple of million gamete mother cells, the oogonia, are formed in each fetal ovary. No fresh oogonia are formed or added after birth. These cells begin meiosis, enter the prophase of the first meiotic division, and stop there; a germ cell paused at this stage is a primary oocyte, and it is diploid with 46 chromosomes. Each primary oocyte becomes surrounded by a layer of granulosa cells, and the whole package is a primary follicle. Large numbers of these follicles degenerate between birth and puberty, so that by puberty only about 60,000 to 80,000 primary follicles are left in each ovary.

From puberty onwards, a follicle continues its development in stages. A primary follicle gains more layers of granulosa cells and a new covering called the theca, and is then a secondary follicle. The secondary follicle soon becomes a tertiary follicle, recognised by a fluid-filled cavity called the antrum; at this stage the theca is organised into an inner theca interna and an outer theca externa. It is inside the tertiary follicle that the primary oocyte grows and finally completes its first meiotic division. That division is unequal: it produces one large haploid secondary oocyte with 23 chromosomes, which keeps almost all of the nutrient-rich cytoplasm, and one tiny first polar body. The tertiary follicle then becomes the mature or Graafian follicle, and the secondary oocyte forms a new membrane around itself called the zona pellucida. The Graafian follicle finally ruptures and releases the secondary oocyte from the ovary; that release is ovulation.

Two comparisons are worth stating plainly. First, on numbers: one primary spermatocyte gives four usable sperms, but one primary oocyte gives only one usable ovum, with the polar bodies taking almost no cytoplasm and playing no further role. Second, on timing and place: in the male, both meiotic divisions happen one after the other inside the seminiferous tubules, and the process runs continuously from puberty. In the female, meiosis I begins in the fetal ovary, pauses for years, and is completed inside the ovary just before ovulation; the second meiotic division is not finished at ovulation at all, and is completed only after a sperm has entered, which happens in the oviduct.

The reproductive cycle in female primates, which includes monkeys, apes and human beings, is called the menstrual cycle. The first menstruation begins at puberty and is called menarche. In human females menstruation is repeated at an average interval of about 28 to 29 days, and the whole sequence of events from one menstruation to the next is one menstrual cycle. One ovum is released in the middle of each cycle. Around the age of about fifty the cycles stop, and that is menopause. Cyclic menstruation between menarche and menopause is an indicator of a normal reproductive phase.

Follow the cycle in four phases, and keep two stories running side by side: what is happening in the ovary and what is happening in the uterine lining.

The cycle starts with the menstrual phase, which lasts about 3 to 5 days. During it, the endometrial lining of the uterus and its blood vessels break down, and the resulting fluid passes out through the vagina. This breakdown happens only when the released ovum has not been fertilised. Absence of menstruation may indicate pregnancy, but it can also be caused by stress or poor health, so it is not by itself proof of anything.

Next comes the follicular phase. In the ovary, the primary follicles grow until one becomes a fully mature Graafian follicle. At the same time, in the uterus, the endometrium regenerates by proliferation, rebuilding the lining that was just shed. Both changes are driven by hormones. Secretion of the gonadotropins LH and FSH from the anterior pituitary increases gradually through this phase. These stimulate follicular development, and the growing follicles secrete oestrogens. Because the endometrium is being rebuilt during this stretch, the follicular phase is also called the proliferative phase.

Both LH and FSH reach a peak in the middle of the cycle, at about the fourteenth day. The rapid rise of LH to its maximum at mid-cycle is called the LH surge, and it is the LH surge that causes the Graafian follicle to rupture and release the ovum. That release is ovulation, and it defines the ovulatory phase. Get the direction of this causal arrow right: the LH surge causes ovulation, ovulation does not cause the LH surge.

After ovulation comes the luteal phase. The remaining parts of the ruptured Graafian follicle transform into a structure called the corpus luteum. The corpus luteum secretes large amounts of progesterone. Progesterone is what maintains the thickened endometrium, and only such an endometrium can receive an implanting embryo and support the events of pregnancy. If fertilisation does not occur, the corpus luteum degenerates. Once it degenerates, progesterone support is withdrawn, the endometrium disintegrates, and menstruation begins, which is the start of the next cycle. If, instead, fertilisation and implantation do occur, all the events of the menstrual cycle stop and there is no menstruation during pregnancy.

A short way to hold the hormone roles together: FSH and LH come from the anterior pituitary and act on the ovary. Oestrogens and progesterone come from the ovary and act mainly on the uterus. Oestrogens dominate the first half of the cycle and are secreted by the growing follicle; progesterone dominates the second half and is secreted by the corpus luteum. The corpus luteum is not a separate gland that appears from nowhere; it is what the emptied follicle turns into after ovulation.

Sperms released into the vagina swim through the cervix, into the uterus, and on to the junction between the isthmus and the ampulla of the fallopian tube. This site is called the ampullary-isthmic junction, and it is where fertilisation takes place. The ovum released by the ovary is also carried to the same junction. Fertilisation can happen only if both the ovum and the sperms reach the ampullary-isthmic junction at the same time, which is why fertilisation does not follow every act of copulation.

Fertilisation is the fusion of a sperm with an ovum. A sperm first makes contact with the zona pellucida, the membrane surrounding the released secondary oocyte. That contact induces changes in the membrane that block any further sperms from entering. This is how it is ensured that only one sperm fertilises one ovum, and it is worth stating the mechanism in that order: contact first, then the block, then entry of that one sperm. The secretions of the acrosome help the sperm pass through the zona pellucida and the plasma membrane and reach the cytoplasm of the ovum.

Sperm entry is also the trigger for the last meiotic step of the female gamete. The secondary oocyte had not finished its second meiotic division; sperm entry induces its completion. This division too is unequal, and it produces a second polar body and the haploid ovum. The haploid nucleus of the sperm and the haploid nucleus of the ovum then fuse, and the result is a diploid zygote with 46 chromosomes. So the female germ cell is haploid at ovulation with 23 chromosomes, but it is technically still a secondary oocyte until a sperm arrives.

The sex of the child is decided at this same moment, and by the sperm. All ova carry an X chromosome. A sperm carries either an X or a Y chromosome, and roughly half the sperms are of each kind. If a sperm carrying X fuses with the ovum, the zygote has XX and develops into a female. If a sperm carrying Y fuses, the zygote has XY and develops into a male. The mother contributes only X, so nothing about the mother determines the sex of the child. The widespread belief that she does is simply wrong, and the chromosome accounting above is the reason.

Now the zygote starts to divide. As it moves down the isthmus of the oviduct towards the uterus it undergoes mitotic divisions called cleavage, forming 2, then 4, then 8, then 16 daughter cells called blastomeres. An embryo with 8 to 16 blastomeres is called a morula. Cleavage keeps the total size roughly the same while increasing the number of cells, so a morula is not bigger than the zygote; it is simply divided into more cells.

The morula continues dividing and becomes a blastocyst as it moves further into the uterus. At this stage the cells stop being alike, and the arrangement is what you must be able to describe in words. The blastomeres of the blastocyst are arranged into an outer layer called the trophoblast, and an inner group of cells attached to the trophoblast called the inner cell mass. The two have different fates. The trophoblast is the layer that attaches to the endometrium. The inner cell mass is the part that differentiates into the embryo itself. After the trophoblast attaches, the uterine cells divide rapidly and cover the blastocyst, so the blastocyst becomes embedded in the endometrium of the uterus. This embedding is called implantation, and it leads to pregnancy.

After implantation, finger-like projections appear on the trophoblast. These are the chorionic villi, and they are surrounded by uterine tissue and maternal blood. The chorionic villi and the uterine tissue interdigitate, that is, they interlock like the fingers of two clasped hands, and together they form a single structural and functional unit between the developing foetus and the mother. That unit is the placenta. Note carefully that the placenta is not made by the foetus alone; it is a joint structure with a fetal contribution, the chorionic villi, and a maternal contribution, the uterine tissue.

The placenta does two quite different jobs, and a full account of it has to cover both. As an exchange surface, it supplies oxygen and nutrients to the embryo and removes carbon dioxide and the excretory or waste materials produced by the embryo. The placenta is connected to the embryo by the umbilical cord, which carries substances to and from the embryo. As an endocrine structure, the placenta produces several hormones, including human chorionic gonadotropin (hCG), human placental lactogen (hPL), oestrogens and progestogens. In the later phase of pregnancy the ovary also secretes a hormone called relaxin. Three of these are produced in women only during pregnancy: hCG, hPL and relaxin. That restriction is the reason the three are described as pregnancy-specific hormones. Besides these, the maternal blood levels of oestrogens, progestogens, cortisol, prolactin and thyroxine all rise several fold during pregnancy. This increased hormone output supports fetal growth, drives the metabolic changes in the mother, and maintains the pregnancy.

Meanwhile the embryo itself is being built from the inner cell mass. Immediately after implantation, the inner cell mass differentiates into an outer layer, the ectoderm, and an inner layer, the endoderm. A third layer, the mesoderm, soon appears between the ectoderm and the endoderm. These three primary germ layers give rise to all the tissues and organs of the adult body. The inner cell mass also contains certain cells called stem cells, which have the potency to give rise to all the tissues and organs.

Human pregnancy runs for about nine months. Some landmarks in that development are worth remembering as a rough timeline. After one month of pregnancy the embryo's heart is formed, and the first sign of the growing foetus that can be detected is the heart sound, heard carefully through a stethoscope. By the end of the second month the foetus has developed limbs and digits. By the end of twelve weeks, that is, the first trimester, most of the major organ systems are formed; the limbs and the external genital organs, for instance, are well developed. The first movements of the foetus and the appearance of hair on the head are usually noticed during the fifth month. By the end of twenty-four weeks, the end of the second trimester, the body is covered with fine hair, the eyelids separate and the eyelashes are formed. By the end of nine months the foetus is fully developed and ready for delivery. When you use this timeline, keep the units consistent: months are used for some landmarks and weeks for others in the standard account, and the trimester boundaries fall at twelve weeks and twenty-four weeks.

The average duration of human pregnancy is about nine months, and this period is called the gestation period. At the end of it, vigorous contractions of the uterus expel the foetus. This delivery of the foetus is called parturition.

Parturition is induced by a complex neuroendocrine mechanism, and the order of events in it is what has to be got right. The signals that begin the process originate from the fully developed foetus and from the placenta. These signals induce mild contractions of the uterus, and this is called the foetal ejection reflex. The reflex triggers the release of oxytocin from the maternal pituitary. Oxytocin acts on the uterine muscle, the myometrium, and causes stronger uterine contractions. Those stronger contractions in turn stimulate still more secretion of oxytocin. So contraction leads to more oxytocin, and more oxytocin leads to stronger contraction. This is a positive feedback loop, not a negative one: the response amplifies the stimulus instead of damping it, which is exactly what is needed for a process that has to run to completion. The loop continues until the contractions are strong enough to expel the baby through the birth canal. Soon after the infant is delivered, the placenta too is expelled from the uterus.

Two points about oxytocin are worth keeping separate. First, the initiating signals come from the foetus and the placenta, not from the mother's pituitary; the pituitary responds. Second, the oxytocin involved is maternal, released from the mother's pituitary, and it acts on the mother's uterine muscle.

Lactation is the production of milk by the mammary glands. The mammary glands undergo differentiation during pregnancy and start producing milk towards the end of pregnancy, so that milk is available when the newborn arrives. The milk produced during the first few days of lactation is called colostrum. Colostrum is not just early milk with a different name; it contains several antibodies, and these antibodies are essential for developing resistance in the newborn baby. A newborn's own immune system has had no exposure to the outside world, so this transfer of ready-made antibodies from the mother is the baby's early protection. Breast feeding during the initial period of infant growth is therefore recommended for bringing up a healthy baby.

Put together, the last stretch of this chapter is a chain of three linked ideas: the gestation period ends with a positive feedback loop of contraction and oxytocin, delivery is followed by expulsion of the placenta, and feeding begins with colostrum whose antibodies give the newborn its first immune protection.