2.

Menstruation, Oocyte Maturation and Sperm Activation

Males and females have hormonal cycles that underlie biological function. Men produce higher levels of
testosterone in the morning, which falls throughout the day.

Women have 28-day cycles that results in peaks and troughs of estrogen and progesterone, which
coordinate the uterus and results in monthly menstrual flow.

These hormones are timed with the maturation of the male sperm and female egg and each of these
cells goes through precise developmental patterns that permits millions of sperm to be released with
each ejaculate and a single high quality egg to be ovulated from the ovary. Understanding the hormones
as they relate to gamete development is our goal for this series of lectures, beginning with the male.

2.1 | Male Hormones and Sperm Activation

Testosterone is under the control of hypothalamic hormone, GnRH, that has a daily or circadian rhythm.
This brain hormone controls the pituitary hormones FSH and LH.

GnRH  LH / FSH  Testosterone

Perhaps somewhat unexpectedly, males do make both Follicle Stimulating Hormone and Luteinizing
hormone. These hormones travel through the circulation and act on the testis to control sperm
maturation and hormone production.

- FSH (follicle development on females) acts on the Sertoli cell to make the hormone inhibin,
which provides the ‘status signal’ back to the pituitary, about the readiness of the testis to
support spermatogenesis.

- LH (ovulating hormone) act on Leydig cells to stimulate testosterone production.

For males at the time of puberty, both the brain centers and the testis need to become coordinated. As
boys transition through this stage of development, there are increasing amounts of each of these
hormones until the hormones establish what is known as a negative feedback loop - where each hormone
controls the 'set point' so there is neither over nor under production of any of these hormones.

"A thermostat works like a negative feedback loop. Once a room gets to the right temperature,
the thermostat shuts off the air conditioner or heater. The same can be said for hormones. Once
the brain senses the right amount, it turns off the production of hormones."

The regulation of male hormones has peak testosterone in the morning falling by up to 25% by evening.
The relatively stable hormone production is in response to relatively constant sperm production. The
male germ cell is known as the sperm and they are produced every day from spermatogonial stem cells.

These stem cells constantly replenish new sperm so that there are at least 1000 sperm produced with
every heartbeat.

Once formed, the sperm are moved into accessory organs known as the epididymis, followed by the vas
deferens. Sperm maturation occurs in the epididymis, not in the testis.

The ejaculate, or semen, contains the sperm and fluids that activate the sperm, as well as an energy
source - fructose; and, prostaglandins to assist with muscular contractions of the female genital tract to
aid in the process of sperm swimming motions.

Sperm are ejaculated through the penis. The penis is an erectile tissue that can be distended curing
sexual arousal.

There are two phases of ejaculation - emission and expulsion.

- During the emission phase, the sperm move into urethra and mix with secretions from the
seminal vesicles and prostate gland. Once semen is in the urethra, the muscles around the penis
shaft begin to contract and the semen is expelled in a series of spurts.

Two factors control an erection. Testosterone and nitric oxide.

- Men have elevated Testosterone in the morning which contributes to morning erections.
- The muscles of the penis are also under the control of nitric oxide, and regulation of nitric oxide
synthase is a major target for drugs that address male erectile dysfunction
2.1.1 | Spermatogenesis
Spermatogenesis is the process by which male primary sperm cells undergo meiosis and produce a
number of cells termed spermatogonia, from which the primary spermatocytes are derived. Each primary
spermatocyte divides into two secondary spermatocytes; and each secondary spermatocyte into two
spermatids or young spermatozoa. These develop into mature spermatozoa, also known as sperm cells.
Thus, the primary spermatocyte gives rise to two cells, the secondary spermatocytes; and the two
secondary spermatocytes, by their subdivision, produce four spermatozoa.

Spermatozoa are the mature male gametes in many sexually reproducing organisms. Thus,
spermatogenesis is the male version of gametogenesis. In mammals, it occurs in the male testes and
epididymis in a stepwise fashion. It takes approximately 64 days in human males. Spermatogenesis is
highly dependent upon optimal conditions for the process to occur correctly, and is essential for sexual
reproduction. DNA methylation and histone modification have been implicated in the regulation of this
process. It starts at puberty and usually continues uninterrupted until death, although a slight decrease
can be discerned in the quantity of sperm produced with increase in age.

Spermatocytogenesis is the male form of gametocytogenesis and results in the formation of

spermatocytes possessing half the normal complement of genetic material. In spermatocytogenesis, a
diploid spermatogonium that resides in the basal compartment of seminiferous tubules divides
mitotically to produce two diploid intermediate cells called primary spermatocytes. Each primary
spermatocyte then moves into the adluminal compartment of the seminiferous tubules, duplicates its
DNA, and subsequently undergoes meiosis I to produce two haploid secondary spermatocytes, which
will later divide once more into haploid spermatids. During this division, there is random inclusion of
either parental chromosome, and chromosomal crossover, both of which increase the genetic variability
of the gamete. Each cell division from a spermatogonium to a spermatid is incomplete; the cells remain
connected to one another by bridges of cytoplasm to allow synchronous development. It should also be
noted that not all spermatogonia divide to produce spermatocytes; otherwise, the supply would run
out. Instead, certain types of spermatogonia divide to produce copies of themselves, thereby ensuring a
constant supply of gametogonia to fuel spermatogenesis.

Spermatidogenesis is the creation of spermatids from secondary spermatocytes. Secondary

spermatocytes produced earlier rapidly enter meiosis II and divide to produce haploid spermatids. The
brevity of this stage means that secondary spermatocytes are rarely seen in histological preparations.

During spermiogenesis, the spermatids begin to grow a tail and develop a thickened mid-piece where
the mitochondria gather and form an axoneme. Spermatid DNA also undergoes packaging, becoming
highly condensed. The DNA is packaged with specific nuclear basic proteins, which are subsequently
replaced with protamines during spermatid elongation. The resultant tightly packed chromatin is
transcriptionally inactive. The Golgi apparatus surrounds the now condensed nucleus, becoming the
acrosome. One of the centrioles of the cell elongates to become the tail of the sperm.

Maturation then takes place under the influence of testosterone, which removes the remaining
unnecessary cytoplasm and organelles. The excess cytoplasm, known as residual bodies, is
phagocytosed by surrounding Sertoli cells in the testes. The resulting spermatozoa are now mature, but
lack motility, rendering them sterile. The mature spermatozoa are released from the protective Sertoli
cells into the lumen of the seminiferous tubule in a process called spermiation.
The non-motile spermatozoa are transported to the epididymis in testicular fluid secreted by the Sertoli
cells with the aid of peristaltic contraction. While in the epididymis the spermatozoa gain motility and
become capable of fertilization. However, transport of the mature spermatozoa through the remainder
of the male reproductive system is achieved via muscle contraction rather than the spermatozoon's
recently acquired motility.

The process of spermatogenesis is highly sensitive to fluctuations in the environment, particularly

hormones and temperature. Seminiferous epithelium is sensitive to elevated temperature in humans
and will be adversely affected by temperatures as high as normal body temperature. Consequently, the
testes are located outside the body in a sack of skin called the scrotum. The optimal temperature is
maintained at 2 °C below body temperature in human males. This is achieved by regulation of blood
flow and positioning towards and away from the heat of the body by the cremasteric muscle and the
dartos smooth muscle in the scrotum. Dietary deficiencies (such as vitamins B, E, and A), anabolic
steroids, metals (cadmium and lead), x-ray exposure, dioxin, alcohol, and infectious diseases will also
adversely affect the rate of spermatogenesis.

Spermatocytogenesis - Diagram of the steps of spermatocytogenesis

Seminiferous Tubule - Micrograph showing seminiferous tubule with maturing sperm.

Spermatozoon - Diagram of a spermatozoon

2.1 | Menstrual Cycle
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