Sex determination in mammals

In most mammals, sex is determined by the XY system of chromosomes. This pair of chromosomes, XX or XY, is called the sex chromosomes. A Y chromosome makes the individual a biological male, while its absence renders it a female. The X chromosome carries the genes that encode the hormone estrogen. This hormone promotes the development of the female reproductive system. The Y chromosome carries a gene known as SRY (Sex-determining Region Y). This gene encodes a protein called the Testis-Determining Factor (TDF). During early development, TDF stimulates the expression of other genes that induce the primordial reproductive tissues to develop into cells that become part of the male reproductive system (Sertoli and Leydig cells). These cells secrete testosterone and the anti-Mullerian hormone, which then promote testis formation.

An overview of the sex-determining system in mammals. The Y chromosome in the embryo causes its gonadal tissues to differentiate into the testis, resulting in a biological male. In the absence of the Y chromosome, the embryo develops into a biological female. Image credit: Bioninja

A flowchart showing the hormonal control of spermatogenesis.

Oogenesis

Oogenesis is the process of forming egg cells in the ovaries. As in human males, the regulation of oogenesis in human females is coordinated by hormones produced in the brain and the ovaries. The hormones produced by the female brain are similar to the ones made by the male brain: GnRH is produced by the hypothalamus. In turn, GnRH stimulates the production of LH and FSH in the anterior pituitary gland.

In females, FSH and LH act on the ovaries. In response, the ovaries will recruit a follicle for maturation (the follicle is a structure that contains an egg cell). This period of follicular maturation is known as the follicular phase. Although each ovary has millions of immature follicles, only one will be recruited to develop a menstrual cycle. In addition to follicle recruitment, the ovaries will release oestradiol and progesterone hormones. As the follicle matures, the concentration of these two hormones in the blood will continue to rise – oestradiol increases more rapidly than progesterone. One of the roles of oestradiol and progesterone is to increase the thickness of the epithelial lining of the uterus (endometrium). As a result, the endometrium also becomes vascularised (filled with blood vessels). This process prepares the uterus for implantation by the embryo.

The oestradiol level will continue to rise during the follicular phase and reach a maximum when the follicle matures. This causes the pituitary gland to release large amounts of LH (known as the LH surge). In turn, the follicle ruptures, releasing the egg cell into the oviduct (fallopian tube). This process is called ovulation. The egg begins its journey through the fallopian tube, being pushed along by the delicate cilia lining it. The remnant of the follicle in the ovary, now called the corpus luteum, begins to secrete large amounts of progesterone, causing its concentration in the blood to rise. This enhances the thickening of the endometrium.

A few days after ovulation, the corpus luteum degenerates. As a result, the level of progesterone in the blood will fall. This triggers the next phase of the menstrual cycle in human females, called the menstrual phase. In this phase, the endometrium breaks down and is discharged through the vagina. This discharge is known as menstruation and signifies that pregnancy has not occurred.

The menstrual cycle is uncommon in mammals—only human females and the females of some primates appear to go through menstruation. The females of other mammalian species have the estrous cycle. The estrous cycle is similar to the menstrual cycle, except that the menstrual phase is replaced with the estrous phase. During estrous, the endometrium is resorbed rather than discharged.

This figure shows the changes in the ovaries and uterus in response to hormonal changes during the menstrual cycle. By Chris 73 / Wikimedia Commons, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=19707

This figure shows the breakdown of the endometrium in the menstrual phase of the menstrual cycle. By National Institute of Child Health and Human Development - http://www.nichd.nih.gov/health/topics/menstruation/conditioninfo/Pages/default.aspx, Public Domain, https://commons.wikimedia.org/w/index.php?curid=41147835

Fertilisation and pregnancy

The egg cell is non-motile (after ovulation, the cilia that line the Fallopian tube push the egg cell towards the uterus), while the sperm cells are motile. Fertilisation is the fusion of a single egg cell with a single sperm cell. Through copulation, semen is introduced into a female's reproductive tract. The sperm cells swim through the layer of mucus that covers the surfaces of the female reproductive tract. The chemical composition of the mucus (for example, the bicarbonate ions) activates the sperm cells. Only those cells that are structurally intact begin the long journey to the Fallopian tubes. It is unclear how the sperm cells are guided to the egg cell in the Fallopian tube, but chemoattraction (chemotaxis) and temperature (thermotaxis) may be involved.

Sperm cells move towards an egg cell. Sperm cells are the smallest cells in humans, while the egg cell is the largest. Image credit: Flickr (CC BY 2.0)

When the sperm cells encounter the egg cell, they attach to its surface. Although many sperm cells may attach to the surface of an egg cell, only one of those sperm cells will successfully fertilise the egg. The egg cell surface has proteins called the zona pellucida proteins (ZP1, ZP2 and ZP3). The sperm cell has proteins that recognise and bind to the ZP proteins. It is only when those proteins interact that a strong binding occurs. The first sperm to successfully attach to the egg cell initiates fertilisation and prevents other sperm from fertilising the egg. This process is called the block to polyspermy (polyspermy means an egg cell fertilised by multiple sperm cells). After attachment, the sperm cell undergoes the acrosome reaction, in which the head of the sperm cell (which contains the nucleus) penetrates the egg cell.

Fertilisation of an egg by a sperm cell. (A) A sperm cell attaches to the egg cell via the Zona Pellucid Protein, ZP3. (B, C)The attached sperm releases enzymes (acrosomal enzymes) that degrade the egg's outer covering (the zona pellucida). (D-E) The sperm cell membrane and the egg cell membranes fuse, causing the sperm nucleus to enter the egg cytoplasm. Image credit: Richard E. Jones PhD, Kristin H. Lopez PhD, in Human Reproductive Biology (Fourth Edition), 2014. Accessed via Science Direct

A detailed view of the fertilisation process. Image credit: Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013. Licensed under the Creative Commons Attribution 3.0 Unported license.

After fertilisation, the egg cell is called a zygote. The zygote initially has two nuclei: the haploid egg nucleus and the haploid sperm nucleus. Soon, the two haploid nuclei will fuse into a single diploid nucleus.

A zygote with two haploid nuclei before fusion. Image credit: Nina Sesina. This file is licensed under the Creative Commons Attribution-Share Alike 4.0 International license.

The zygote will undergo a series of mitotic divisions (each cell division is called a cleavage). The multicellular structure is called an embryo and continues to travel towards the uterus. Soon, the embryo becomes a solid spherical mass of cells called a morula. Then, some of the cells in the interior of the embryo die, and that space becomes filled with fluid. The embryo is called a blastula. The embryo (blastula) attaches to the uterine wall in the uterus. By this stage, the embryo reaches the uterus. It connects to the wall (endometrium) of the uterus. A group of cells in the embryo called the inner cell mass divides and invades the endometrium. Eventually, they will develop into the placenta. The placenta is the interface between the embryo and maternal blood circulation. The transfer of gases, nutrients and wastes occurs across the placenta.

The placenta also functions as an endocrine organ and produces the hormone human chorionic gonadotropin (hCG). hCG ensures that pregnancy continues until the baby is born and prevents further cycles of ovulation.

This figure shows the journey of the egg from the ovary. After fertilisation in the Fallopian tube, the embryo implants in the uterine wall, thus establishing a pregnancy. Image credit: Ttrue12. This file is licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license.

This table shows the average gestation times for a range of viviparous mammals. Data from Wikipedia: List of mammalian gestation durations. Distributed under the Creative Commons Attribution-ShareAlike License.

Birth

In placental mammals (including humans), after the placenta is formed, the mother's biology adapts to maintaining the pregnancy. Two hormones are essential to this: estrogen and progesterone. Estrogen is produced initially by the corpus luteum in the ovary and later by the fetus, while the placenta produces progesterone. Both of these hormones work in concert to maintain the pregnancy (e.g., strengthening the uterine walls to support the growing fetus, preventing the contraction of the uterus, and developing the mammary glands for lactation).

Birth is the process of externalising (bringing forth) the young animal. Scientifically, birthing is referred to as parturition. Birthing is complex and coordinated by various systems, such as the nervous and endocrine systems. The endocrine control of birth involves both positive and negative feedback. The following description provides an overview of some events that occur during labour and birth in human females (not that the description is incomplete).

1. As the fetus grows, the uterine muscles stretch, causing the placenta to release estriol hormone.

2. Estriol inhibits the release of progesterone from the placenta, lifting the block to quiescence (i.e., preventing the contraction of the uterine muscles).

3. Estriol also stimulates the release of oxytocin (a hormone) from the pituitary gland. The oxytocin hormone binds to receptors on uterine muscles, promoting muscle contractions.

4. The contraction of the uterine muscles stimulates the estriol-oxytocin pathway. This positive feedback pathway increases the intensity and frequency of contractions, leading to the birth of the child. The release of chemicals called prostaglandins by the fetus further promotes uterine contractions.

5. Oxytocin and prolactin (another hormone) stimulate milk production in the mammary glands.

Understanding hormonal control of pregnancy and birth

Students learning this topic may find it useful to consider the various stages of mammalian reproduction as a series of developmental events. For example, gamete production, pregnancy and birth represent specific developmental events that are regulated by hormones. In females, the reproductive system serves three distinct events associated with reproduction: ovulation, pregnancy and birth. The brain regulates these events by secreting hormones and responding to hormones produced by the reproductive organs and the fetus. This two-way communication is important for a successful pregnancy and birth, including post-natal care (milk production). The hormones involved in this complex communication between the brain and the reproductive system form the brain-gonad axis - specifically, the hypothalamic-pituitary-gonadal axis. As with all hormonal systems, positive and negative feedback loops regulate the biological processes. For example, in both males and females, LH and FSH from the pituitary gland stimulate the production of gametes in the gonads. In females, progesterone prepares the uterus for the embryo's implantation and the pregnancy's maintenance. During birth and post-natally, oxytocin causes the expulsion of the fetus during birth (pa

Hormonal control of spermatogenesis. Biological organs are shown in the white text boxes, while the hormones produced are in the purple text boxes. Stimulatory actions (+) are shown as green arrows, while inhibitory actions (-) are red arrows. LH stimulates (+) the Leydig cells to produce testosterone. In the presence of testosterone and FSH, the Sertoli cells produce sperm cells. In addition, the Sertoli cells produce two hormones, inhibin and estradiol. The three testicular hormones, testosterone, inhibin and estradiol, feedback negatively on the hypothalamus and pituitary, resulting in a decrease in the production of LH and FSH.

Hormonal control of oogenesis and pregnancy. Biological organs are shown in white text boxes, while the hormones produced are shown in purple text boxes. Stimulatory actions (+) are shown as green arrows, while inhibitory actions (-) are shown as red arrows. LH and FSH stimulate (+) the recruitment of a follicle in the ovary (to mature into an oocyte). The follicle, in turn, produces estradiol (estrogen). Estrogen inhibits the release of LH and FSH from the pituitary gland. As a result, no further follicles are recruited. After ovulation, the follicle becomes the corpus luteum, which secretes progesterone. Progesterone thickens the endometrium of the uterus and prepares it for implantation by the embryo. Progesterone also feeds back negatively on the hypothalamus and the pituitary gland to prevent further ovulation.

Perspectives

Hormonal control of mammalian reproduction is complex - the descriptions provided in this webpage cover only some aspects of that system. The hormones ensure that the organs of the reproductive system function as an orchestrated sequence of events, where the hormones themselves are the conductors of the symphony. In all non-oviparous mammals, maternal and fetal hormones regulate pregnancy and gestation so that the fetus develops in an optimal environment before birth. This includes the regulation of metabolic, respiratory and other physiological systems. Similarly, the interplay of material and fetal hormones stimulates birth.

It is important for students to note that the testis and ovaries are both reproductive and endocrine organs.