Next Lesson - Sex, Infertility and Contraception
Core
Gametogenesis - the process of making sex cells (gametes) through meiosis. This occurs in the testes in males, and in the ovaries in females.
Spermatogenesis is the process that creates sperm from primordial germ cells (the earliest cells that go on to become sperm or eggs) in the testicles. It has a number of steps, which are listed below and included in the diagram:
- The primordial germ cell divides by mitosis to produce spermatogonia (the dividing cells in the testis that start sperm production).
- The spermatogonia divide by mitosis to produce two types of cells:
- Type A Spermatogonium - divides to renew the supply of spermatogonia, and will go on to divide into type A and type B spermatogonia in the future.
- Type B Spermatogonium - continue along the spermatogenesis pathway to produce sperm.
- Type B spermatogonium divides by mitosis to form primary spermatocytes.
- Primary spermatocytes divide by meiosis I (the first meiotic division) to form secondary spermatocytes.
- Secondary spermatocytes go through meiosis II (the second meiotic division) to turn into spermatids (round, immature sperm cells).
- Spermatids continue through spermiogenesis to produce sperm cells.
Spermiogenesis is the final stage in the production of sperm cells and involves the transition of spermatids into sperm cells (spermatozoa). These sperm cells cannot swim yet. They become motile (able to swim) later, in the epididymis (the coiled tube next to the testis, where sperm mature and are stored), as described below.
Spermiation is the outcome of spermiogenesis. Spermiation occurs when the sperm cells are released into the lumen of the seminiferous tubules (the coiled tubes in the testis where sperm are made). They then pass through the rete testis and ductuli efferentes (a network of small ducts that carries sperm out of the testis) and into the epididymis. Sperm cells are not motile until they pass through the epididymis. Before this, they are transported by secretions from Sertoli cells (supporting cells in the seminiferous tubules) and peristalsis, and after transit through the epididymis, they acquire motility and become mature sperm cells.
Diagram - Spermatogenesis and spermiogenesis
SimpleMed original by Dr. Maddie Swannack
Capacitation of sperm is the final step before sperm becomes able to fertilise an oocyte. Capacitation occurs in the female reproductive tract following ejaculation. It involves the removal of glycoproteins (proteins with sugar chains attached) and cholesterol from the sperm membrane and activation of signalling pathways inside the sperm cells. Removal of the glycoproteins allows the sperm to bind to the zona pellucida (the protective coat around the oocyte). Binding to the zona pellucida then triggers the acrosome reaction (a change in the acrosome, the cap-like structure on the sperm head). The acrosome reaction is the process that allows the sperm to penetrate the egg cell and begin fertilisation.
Capacitation is an important consideration for in vitro fertilisation (IVF, where the egg is fertilised in a laboratory). As the sperm never encounters the female reproductive tract before meeting the egg, the sperm must be treated in a capacitation medium to trigger the process artificially. In ICSI (intracytoplasmic sperm injection, where one sperm is injected directly into the egg), the sperm does not bind to the zona pellucida, so the binding and acrosome reaction steps are bypassed.
Not all the stages of spermatogenesis are visible histologically (when a thin slice of tissue is viewed under a microscope) in a single cross-section of a seminiferous tubule. New generations of sperm cells start developing without waiting for the earlier generations to finish, so different stages sit side by side along the tubule. This suggests that sperm are produced continuously rather than in batches.
The spermatogenic cycle is the time taken for the same stage of spermatogenesis to appear in the same segment of the seminiferous tubule. In humans this takes around 16 days. The total time to produce one fully mature sperm cell from a spermatogonium is about 74 days in humans.
The spermatogenic wave is the appearance of the different stages of spermatogenesis in the seminiferous tubules in a sequential and ‘wave-like’ pattern along the tubule. This wave-like pattern is the spermatogenic wave.
The oocyte (pronounced o-o-cyte not oo-cyte) is the female gamete and is also known as an egg cell. A woman is born with all her oocytes formed but not fully developed in her ovaries. This stock declines after birth with age due to atresia (cell death).
Formation of oocytes begins before birth. Germ cells differentiate into oogonia (the cells that give rise to oocytes) and proliferate by mitosis. The oogonia then begin meiosis, but arrest in prophase I (meaning they have started the first meiotic division but paused part-way through it, and do not complete it until just before ovulation). At this point, the oogonia become primary oocytes. At birth, these primary oocytes number roughly 500,000 to 1 million (older sources quote up to 2 million), and each one is surrounded by a flat layer of epithelial cells called follicular cells. The primary oocytes surrounded by follicular cells are named primordial follicles.
Most of these primordial follicles undergo atresia during childhood, leaving roughly 200,000 to 400,000 in the ovaries by the start of puberty. From puberty onwards, about 15-20 follicles (each an oocyte with its surrounding cells) begin to develop in each menstrual cycle, but usually only one completes maturation and is ovulated, with the remainder undergoing atresia.
As primordial follicles grow, the epithelium (the layer of cells around the oocyte) changes from flat to cuboidal (cube-shaped). These cuboidal cells are the granulosa cells. A layer of theca interna cells (the inner layer of cells around the follicle) also develops outside them. A layer of glycoprotein named the zona pellucida forms around the oocyte. Which cells make it in humans is still debated. The theca interna cells become paracrine tissue (tissue that sends signals to nearby cells). Under the influence of luteinising hormone (LH), they make androgens (male-type sex hormones, such as testosterone). The granulosa cells then turn these androgens into oestrogen.
As development continues, fluid-filled spaces appear between granulosa cells. These coalesce (join together) to form the antrum, the single fluid-filled cavity of the follicle. Several follicles (15-20) begin development every menstrual cycle but only one progresses to the preovulatory stage.
An increase in follicle-stimulating hormone (FSH) and LH induces growth of the follicle. Just before ovulation, a surge in LH (a sharp rise) makes the primary oocyte resume meiosis I, which was paused in prophase I before birth. During this division the cytoplasm is not evenly distributed. The majority is given to the secondary oocyte and the minority to the first polar body. The polar bodies never become an egg and in effect are dustbins for unneeded genetic material. The secondary oocyte then enters meiosis II and halts at metaphase II (a stage part-way through the second division) until it is fertilised.
Before ovulation occurs, the fimbriae (the finger-like ends) of the fallopian tube (the tube that carries the oocyte to the uterus) sweep the surface of the ovary. Around ovulation, the tube also shows peristaltic action and ciliary beating (the beating of cilia, tiny hair-like projections on the cells lining the tube). Both are believed to help move the oocyte, although how much each contributes is still debated. This means that as soon as ovulation occurs, the fallopian tube is ready to start moving the oocyte towards the uterus.
Ovulation occurs when the graafian/ovarian follicle (the follicle containing the secondary oocyte) grows to roughly 2 cm across (the final size varies, from about 17 to 26 mm). The LH surge increases collagenase activity (an enzyme that breaks down collagen), and prostaglandin (a local signalling chemical made from fatty acids) release causes ovarian wall contractions. This weakens the wall of the follicle until it ruptures, and the oocyte is released from the ovary.
The fallopian tube then acts to move the oocyte into the uterus through peristaltic contractions and fimbriae movements. The fallopian tubes are also lined with cilia which help to waft the oocyte towards the uterus.
As the oocyte leaves the ovary, the surface of the ovary ruptures (tears), so repeated repair is needed. Repair needs extra cellular proliferation (cell division) at these sites. The incessant ovulation hypothesis suggests that this may increase the risk of some types of ovarian cancer. The risk is lower in women who ovulate fewer times in their lifetime. The hypothesis is still debated. For example, it cannot explain why hysterectomy (removal of the uterus) and tubal ligation (cutting or tying the fallopian tubes) also seem to lower the risk. Some ovarian cancers are thought to start in the fimbriae (the finger-like ends) of the fallopian tube.
Preventing ovulation may therefore be a protective factor for ovarian cancer. The risk is lower in multiparous women (women who have had more than one child; ovulation pauses during pregnancy), in women who breastfeed, and in women who use birth control methods that prevent ovulation (such as the combined oral contraceptive pill).
Mittelschmerz is the ovulation pain that some women feel in the lower abdomen around the middle of the menstrual cycle. It is benign (not harmful). It is not known for certain what causes the pain. One theory is that fluid or blood from the follicle irritates the abdomen. Another theory is that the rise in LH makes the smooth muscle around the follicle contract, through prostaglandins, and that this may cause pain. Alternatively it is thought that if the epithelium of the ovary is too well innervated (supplied with nerves) when the oocyte ruptures from the ovary, the rupture can cause pain. The name is German: ‘schmerz’ means pain and ‘mittel’ means middle. The pain is felt in the middle of the menstrual cycle, around ovulation. Ovulation is about 14 days before the next period, so it falls on about day 14 of a 28-day cycle. Do not assume that abdominal pain in a woman is Mittelschmerz. Other causes must be considered. In a woman of reproductive age, think about a pregnancy test, because ectopic pregnancy (a pregnancy that implants outside the uterus) can cause abdominal pain, a missed period or vaginal bleeding.
Diagram - Processes from meiosis to fertilisation
SimpleMed original by Dr. Maddie Swannack
The corpus luteum (literally ‘yellow body’) is formed from the remains of the ovarian follicle (graafian) including the remaining granulosa and theca interna cells. As the cells become vascularised (supplied with new blood vessels) they change into yellow coloured lutein cells. The corpus luteum secretes oestrogen and progesterone. These stimulate the uterine mucosa (the endometrium, the lining of the uterus) to enter the secretory stage (the second half of the menstrual cycle) to prepare for implantation of the embryo.
If fertilisation occurs, the implanted embryo releases β-hCG (beta human chorionic gonadotrophin, the pregnancy hormone). This prompts the corpus luteum to grow and form the corpus luteum graviditatis (the corpus luteum of pregnancy). It continues to secrete progesterone until around 7 to 10 weeks of pregnancy, when the placenta takes over progesterone production. The progesterone released maintains the thick lining of the endometrium.
If the corpus luteum does not receive β-hCG signals from the implanted embryo within around 14 days, it dies and turns into the corpus albicans.
The corpus albicans (literally ‘white body’) is essentially scar tissue formed from the regressed corpus luteum. As the corpus luteum regresses, it stops releasing progesterone. The fall in progesterone (progesterone withdrawal) makes the endometrial lining break down, which is observed as menstruation.
Table - Differences between spermatogenesis and oogenesis
SimpleMed original by Dr. Maddie Swannack
Edited by: Dr. Ben Appleby
Reviewed by: Dr. Thomas Burnell and Dr. Marcus Judge
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