REPRODUCTION

Day 1

First we have to establish biological sex, then we need to have the appropriate

reproductive anatomies, then we need to produce gametes, then we need to unite those gametes

(fertilization) and then we need the result of fertilization to develop. Biological sex in most

species produces exclusively females. If you went to a beehive, every single organism in that

collection will be females. The only time a male is made is for the purposes of fertilizing the

queen. When that is necessary, the larval stages of the bee are provided particular male defining

factors to induce the formation of a male of the species. The only way to get a male is to have

these specific unique factors present during development. The same thing with humans; every

single embryo would be a female if male factors were not provided.

There are four different biological sexes. There is chromosomal sex, gonadal sex,

phenotypic sex, and secondary sexual characteristics. These are established at different points in

our lives. We are familiar with the differences that occurred in our bodies associated with

puberty, those are our secondary sexual characteristics, the physical form that the male and

female possess as adults are their secondary sexual characteristics. Reproductively, the female

can only produce gametes that have X chromosomes, she can only specify the formation of

another female. The male can produce a gamete with either an X or a Y chromosome. The

chromosomal sex of an individual is established at the time of fertilization and depends on the

chromosomal makeup of the fertilizing sperm. The absence of a Y makes you a female, and the

presence of a Y makes you male. All human embryos from that point on are exactly the same;

they have the same internal structures, the same external structures. The only way you are going

to deviate from that pattern of development is if specific male defining factors are present.

The next biological sex that needs to be established is gonadal sex. Prior to the

establishment of gonadal sex, all embryos have what are called gonadal ridges. The gonadal

ridge can form either testes or ovaries. The ovary will form by default; to become the male

gonad, there is a particular gene sequence expressed on the Y chromosome called TDF, testicular

defining factor, which causes the gonadal ridge to become testes, and that happens at about 8

weeks after fertilization. Most of us probably know that the X chromosome has about 2,500

genes and the Y chromosome has less than 20 genes on it, and all of these genes code for male

traits.

Once you have a gonadal sex, the next thing you need to do is connect your gonad to the

outside world, so the next thing you need to develop is what is called an internal phenotype. For

example, the female ovary is found within the abdomen, and to fertilize, the male reproductive

cells must reach the female reproductive cells, so we need to connect that gonad to the outside

world, and the structures that connect the ovary to the outside world is the female internal

phenotype. At this point, the embryo has two sets of internal structures: it has a müllerian duct

and a wolfian duct. The müllerian ducts become the female internal phenotype and the wolfian

ducts become the male internal phenotype. To be a female, if there are no male defining factors,

the müllerian ducts become three things, and these things allow the gonad to be connected to the

outside world: fallopian tubes, uterus, and part of the uterus which connects to the vagina called

the cervix, this region is called the proximal vagina. The distal vagina, the part that passes

through the pelvic floor, is actually part of the outer body wall, but the part that connects the

vagina to the uterus is derived from the müllerian ducts. The male internal phenotype is derived

from the wolfian ducts; during this developmental stage of embryological life, the testes are still

inside the abdominal cavity. Later on, the testes will descend out of the abdominal cavity

through an opening in the abdominal wall called the inguinal canal, and then descend down into

the scrotum, but at this point there is no external phenotype, this is completely internal. We need

to connect the testes to the outside world, so the male system that connects the testes to the

outside world joins up with the urinary system, so the actual connection to the outside world is

via a part of the urinary system, because the urethra connects the bladder to the outside world.

For females, the urethra terminates on the body’s surface; for males, the urethra passes through

the male copulatory organ. So to connect the gonad to the outside world, we do not really

connect it to the outside world, we connect it to the urinary system. The testis is connected to the

urethra by the male internal phenotype; its components include the epididymus, which is where

sperm are stored, the vas deferens, which is the tube that connects the epididymus to the seminal

vesicle, and then when those two structures come together they form what is referred to as the

ejaculatory duct, and that passes through another gland called the prostate. The male internal

phenotype is the epididymus, the vas deferens, and the ejaculatory duct.

Now we have connected the male gonad to a structure that is connected to the outside

world, which is the urethra. The wolfian ducts, if the appropriate male defining factors are

present, will become the epididymus, the vas deferens, and the ejaculatory duct. Now how do

we get this to happen? To become a male, you need two things to happen, you have to stop the

female system from developing and you have to make the male system develop. In a normal

male, TDF causes the testes to form, and the testes produce two factors, MIH, which stands for

müllerian inhibiting hormone, which blocks the müllerian ducts from developing, and

testosterone, which causes the wolfian ducts to develop. If both of those factors are present, then

the internal phenotype becomes male. If you had MIH but not testosterone, you would have no

internal phenotype. If you had testosterone but not MIH, you would have both.

Now that we have an internal phenotype, we have to develop the external phenotype.

During embryological life, the external structures on all embryos are exactly the same. If you are

a male, you do not acquire male characteristics until maybe the eighth or ninth week after

development has started. All embryos have a genital tubercle, a urethral groove, a urethral fold,

and labioscrotal swelling. All embryos start with the same physical appearance comprised of

these four structures. Depending on whether male defining factors are present or absent, these

structures with either become female external genitals or male external genitals.

If there are no male defining factors, the genital tubercle becomes the clitoris, the urethral

groove becomes the vestibule, the urethral fold becomes the labia minora, and the labioscrotal

swellings become the labia majora. If the male defining factors are present, the genital tubercle

becomes the glans which is the most distal end of the penis; the urethral groove becomes what is

called the spongy urethra. The urinary urethra, the tube that connects the bladder to the surface

of the body, needs to be extended all through the penis, and so the urethral fold folds around the

urethral groove, and then the spongy urethra extends up to that space inside of the penis, and

becomes what is called the spongy urethra. The urethral fold becomes the base of the penis, and

the labioscrotal swellings become the scrotum.

From a clinical standpoint, if you were to examine the male external genitals, you will

notice there is a fusion line that runs right up the midline, from the base of the scrotum all the

way up to the base of the penis, because all of the female structures come together and fuse on

the midline, so what would be the labia minora fuses along the midline and becomes the scrotum,

and the testes later on will descend down out through the inguinal canal inside this flab of skin.

In order to get a male external phenotype, you need a male defining factor, and that is

testosterone—the same factor that causes the production of the male internal phenotype also

produces the male external phenotype. Let us say we have a normal male that produces TDF,

gets testes, produces MIH, produces testosterone; the internal phenotype is male, the external

phenotype is male. What if a male produced TDF, got testes, produced MIH, but did not

produce testosterone? The internal phenotype would be nothing, the external phenotype would

be female. What if the male produced TDF, got testes, produced testosterone, but did not

produce MIH? The internal phenotype would be both, the external phenotype would be male.

What if the male had TDF, got testes but produced neither MIH nor testosterone? The internal

phenotype would be female, and the external phenotype would be female. What if we had a

female, of course she is never going to make TDF because she does not have a Y chromosome,

so therefore she is always going to have ovaries, never going to produce MIH; but what if the

pregnant female had a tumor in her adrenal cortex that produced testosterone, and this

developing embryo was exposed to the testosterone from the mom? The internal phenotype

would be both, because she has no MIH but has testosterone, and the external phenotype would

be male.

Day 2

Last class we established biological sex, and the next thing we want to talk about is the

establishment of secondary sexual characteristics, reproductive anatomy, and gametogenesis.

Most of us are pretty familiar with the biological changes that take place during puberty,

those are what are referred to as secondary sexual characteristics. Those physical changes occur

to permit organisms to participate in the behaviors necessary to reproduce, and also allows those

changes to coincide with stages where anatomically reproduction is possible, and this is probably

more true for women. If reproductive maturity was achieved prior to skeletal maturity, then the

fetus could never escape the pelvic floor; if you have ever seen the skeleton of the pelvis, it is

fused in the front and in the back, and then there is an outlet to the bottom. The dimensions of

that outlet have to be large enough to permit the fetus to leave the body, and that cannot happen

in a typical eight year old or ten year old young woman, it has to occur once the skeleton

matures. We do not need it to reach final adult proportion, but it has to be large enough to permit

the fetus to escape, and that is usually sometime between 12 and 14. Coincident to that is when

the reproductive system will produce gametes. Puberty occurs earlier for women than it does for

men because males of most species are larger and stronger than the female, so there is a delay for

the male achieving sexual maturity to allow the female some few years of advanced development

before the male catches up.

Let us look at female puberty first. The one thing about female puberty is that there is a

signatory event that occurs that signals that reproductive maturity is going to be achieved. The

menarche is the first time the endometrium is shed; that is not menses (menstruation); menses

will result when an endometrium that was prepared for implantation is not used: fertilization

does not occur, implantation does not occur, therefore the endometrium is shed. The

endometrium that is shed during menarche is not the same—there is no ovulation, and the

changes necessary to permit implantation have not occurred—it only results from proliferative

growth. Menarche, when it occurs, is probably about six to nine months before a woman can

actually begin ovulating. It is a signatory event: it indicates that sexual maturity is coming, but it

does not indicate that it has occurred yet. So when that endometrium was shed, it did not result

from an egg being ovulated and not fertilized, but instead from a cumulative growth of the

endometrium over many months or years, leading up to that point in time.

The process of female puberty takes years. This represents birth, and let us say the

average female ovulates by the time she is 14. If you look at FSH and LH, the gonadotropins

from the anterior pituitary, and you look at the levels of the gonadotropins, they begin to rise a

couple years before puberty and stay elevated until 45 or so, and then a woman will stop

ovulating. If you zoom in on the years proceeding reproductive maturity, and you look at a 24

hour cycle, and you look at FSH and LH levels across that 24 hour cycle, they are elevated at

night. This does not happen once you reach sexual maturity, so FHS and LH levels are released

during sleep. FSH is follicle stimulating hormone; within the ovary, the eggs are held in

structures called follicles, and the follicles mature under the influence of FSH, and produce

estrogen. Estrogen is an endocrine hormone that affects a lot of reproductive tissues in a

woman’s body as well as other tissues. The secondary changes that we see during puberty for

women are primarily the effects of estrogen. Women will accumulate subcutaneous adipose,

adipose within the lobules of the breast, and also specific types of skeletal structures will grow.

The pelvis will become broader, and thus so will the outlet in the pelvic floor, to ultimately

permit childbirth. Once you reach sexual maturity, these things cycle on a 28 day cycle, then it

will be a menstrual cycle.

One of the other effects of estrogen is to cause the endometrium of the uterus, the inner

lining of the uterus, to thicken. The endometrium will stay thickened as long as there is estrogen

available. After some critical amount of thickening of the endometrium, if estrogen levels drop,

the endometrium will be shed, and that is what we called menarche, but that is not the same thing

as menses. During the normal menstrual cycle, after the egg is released and ovulated, there is an

additional hormone produced called progesterone that causes the endometrium to become

vascular and glandular to permit implantation. That does not happen during the phase that leads

up to ovulation, that phase is only controlled by estrogen. Menarche is the shedding of the

endometrium that has been formed under the influence of estrogen. Menarche occurs, and it

might happen a couple more times before ovulation can actually occur. Once ovulation occurs,

when the endometrium is shed, that is true menses.

As far as male puberty is concerned, male puberty is primarily the effect of testosterone.

If this is birth, males are probably about 15 or so when they can begin producing gametes. If we

look at testosterone levels, remember there is a little glip of testosterone back here in

embryological life; then testosterone levels will begin to increase a few years before puberty,

peak sometime in the early twenties, and then slowly drop but stay sufficiently elevated

throughout life, so males can make gametes throughout their entire lives. Why do women stop

ovulating in their early forties and men continue to produce gametes throughout the rest of their

lives? We did not live long enough. When you go back to social security in the 30s, average life

span was 63, you were never supposed to collect social security, you were supposed to be dead.

It was statistically designed based on assumptions that people live a few years past 60, and we

thought we will make sure they cannot start collecting until they are dead, and then we will have

plenty of money. But now, if someone is alive when they are 50, they are expected to live until

they are 85. Average lifespan for a female is 83 now, average lifespan for a male is 79. During

biological evolution, you are supposed to be dead when you are 50. Why do you stop ovulating

when you are 42? Well, how long does it take before a newborn acquires enough physical

capacities to live independently of its mom? Probably 6-8 years in the biological world. But

why do the men continue to be able to reproduce until the day they die? Because they were

never involved in that part of reproduction, they were there simply to fertilize the eggs, they had

no role in nurturing and caring for the offspring.

All of the effects we see during puberty for males are attributable to testosterone. There

will be a rapid phase of linear growth, males will grow 3-4 inches a year for 3-4 years in a row;

they can grow a quarter more in less than four years. The pectoral part of the skeleton widens,

deltoids, latissimus and pectoral muscles thicken. Then you get various patterns of hair

development, like thickening of the beard and auxiliary and anal-genital production of hair. For

some men, one of the laryngeal cartilages thickens and the tonal quality of the voice becomes

much deeper. Then testosterone viralizes the male nervous system and elicits many stereotypic

patterns of behavior. In lower animals, the actual hormone is what induces reproductive

behavior; for men, it just increases what is called receptivity. For males, on a 24 hour cycle, if

we look at testosterone levels, men are receptive all the time, but most receptive in the morning

and at night. Female receptivity parallels estrogen levels, and estrogen levels increase right

ahead of ovulation, so women are most receptive right ahead of ovulation, which makes sense

reproductively that the female becomes receptive when it is most likely that she will be able to

reproduce.

Let us talk about reproductive anatomy. We will start with the male system first, which

is a little bit more complicated than female. Hormonally, the female system is much more

complicated.

We will start with the gonad itself. The gonad is divided into regions called lobules.

Within each lobule, there are multiple tubes, called seminiferous tubules. If you looked at the

tube, it has an opening in the middle called the lumen and all of the reproductive cells. As

gametogenesis (the process of making gametes) takes place, the male’s cells are migrating from

the outside of the tube to the inside of the tube, and ultimately the spermatocytes are released

into the inside of the seminiferous tubule. In addition to these tubules, there are other cells

within the testis called the leydig cells, which make testosterone. The seminiferous tubules are

the site where spermatogenesis takes place; there are multiple seminiferous tubules within each

lobule, and there are multiple lobules. In addition to the leydig cells, each of the cells that are

developing, the spermatocytes, are surrounded by another other cell called the sertoli cell. These

spermatocytes are held within this other cell. To summarize, the testes are made of regions,

lobules, and each one of the lobules have seminiferous tubules; the tubules are where the sperm

are made; the cells that are developing are surrounded by sertoli cells. In addition to the

seminiferous tubules, between the tubules are leydig cells, and those are the ones that make

testosterone.

The testis is held outside the body. The sperm are temperature sensitive, so they need to

be in an environment that is cooler than the internal environment of the abdominal cavity. The

sperm are made in the seminiferous tubules, and when they are finished they are then stored in

another tube that is folded up in a little membrane attached to the side of the testis, and this is the

epididymus. The epididymus is a place to store the sperm after they have been made.

When the sperm are going to be used for reproductive purpose, they need to be

transported back into the abdominal cavity. There is a little duct called the vas deferens; the vas

deferens comes back in and enters through an opening in the wall of the abdominal cavity called

the inguinal canal. Some men actually get what are called inguinal hernias, where a loop of

intestine will push through that opening and end up outside of the abdominal wall held within the

scrotum, the flab of skin that holds the testis and epididymus. The testis and epididymus are held

within a thin layer of skin called the scrotum, and the scrotum has smooth muscle inside of the

skin so that the physical dimensions of the scrotum can change. When the temperature of the

testis gets too cool, the muscles will contract and pull the testis up against the abdominal wall,

and if the temperature increases, that muscle will relax and the testis will fall away from the

abdominal wall.

The tube, vas deferens, enters into the abdominal cavity. Sperm cannot swim, they do

not acquire the ability to swim until they are actually inside of the female reproductive tract. The

actual epididymus is about 35 inches long, and the vas deferens is 14 inches long. That is 49

inches just to get to the urethra, and the urethra is another six or seven inches, and then you get

inside the female reproductive tract which is probably about another 8-10 inches from the vagina

up to the fallopian tube. Sperm are about 10 micometers. If you took the ratio between the size

of the sperm and the size of a human, and the relative distance each would have to swim,

comparatively a human would have to swim from here to California, 3,000 miles. They are not

going to be swimming around inside the epididymus, they are not going to be going down the

gym and getting buff, they are just going to be hanging out, watching ESPN and drinking, the

things that guys do best. They are not physically active at all. The sperm will be transported up

through the vas deferens; the vas deferens actually contracts, and men can feel the sensation of

the internal duct system contracting, they know prior to ejaculation that the internal duct system

is contracting. The tube has smooth muscle in it; it contracts, and then along the way the sperm

are suspended in various fluids. There are a number of glands, the seminal vesicle provides most

of the fluid and hence the word semen, for the name of the fluid that the sperm are suspended in.

The duct of the seminal vesicle joins up with the vas deferens to form the ejaculatory duct which

then passes into another gland called the prostate gland, and that is where the ejaculatory duct

connects to the urethra. The urethra is the duct that connects the bladder to the outside world, so

the male ejaculatory duct passes into the prostate and joins up with the urethra. The prostate

produces some fluids, but most importantly it has two little muscular sphincters that control the

movement of fluids. To reproduce effectively, you cannot be suspending your sperm in urine,

you have to keep the urinary fluids separate from reproductive fluids. The urethra will ultimately

terminate at the body’s surface. Inside of the prostate are two small muscles, one that holds back

the reproductive fluids and the other that prevents urine from mixing with those fluids.

The ejaculatory duct now joins up with the urethra and along the way, there is another

gland called the bulbourethral gland, sometimes called the Cowper’s gland. So there are three

different glands: the seminal vesicles, the prostate, and the bulbourethral glands that make up the

fluids that suspend the sperm. If a male ejaculates, he cannot urinate a number of minutes

thereafter. The prostate sphincter closes, preventing urine from mixing. There might be some

residual sperm left in the urethra after ejaculation, but the two processes are completely separate.

If the male ejaculates, he cannot urinate, but if he has not ejaculated he still retains the capacity

to urinate, so that blockage of the urinary tract only coincides with ejaculation. The

bulbourethral glands produce a fluid that is released immediately prior to ejaculation to

neutralize the conditions within the urethra.

The urethra extends through the center of the penis; the male copulatory organ is not

perpetually in a condition that permits copulation. The male copulatory organ has to be

pressurized and create what is called turgor pressure to allow it to participate in penetrative sex.

Internally, within the penis, there are two vascular spaces that run the length of the organ, and

these are called the corpora cavernosa and corpora spongiosum. These are vascular spaces.

During behaviors that lead up to copulation, the arteriole blood supply to these areas

become very permeable and the fluid, the actual fluids of the blood, not the blood itself, fill these

spaces, and simultaneous to that the increasing dimension of these internal vascular spaces

compresses return blood flow out of the organ, and as a consequence blood is pumped in but

cannot leave. As you pump more and more fluid into the penis and prevent release of blood out

of that organ, the volume increases, pressure increases, it becomes rigid and can now participate

in copulatory behavior. In order for the male to participate in copulatory behavior, there has to

be sufficient rigidity to allow penetration into the female reproductive tract, and that requires

vascularizing this space.

This is all controlled by the nervous system. There are what are called spinal reflexes;

the spinal cord is connected to these vascular spaces and it is completely reflexive. A male does

not need a brain in order to achieve an erection or ejaculate. The nerves that enervate this space

release a neurotransmitter that is actually gaseous, it is nitric oxide. Nitric oxide causes

vasodilation of these tissues, and then the nitric oxide is broken down into an inactive form. All

of those erectile dysfunction drugs block the breakdown of nitric oxide, leaving it in the tissue to

continue making the tissues permeable. Any time, in a capillary bed for example, blood enters

the capillary, the fluid of the blood leaves the capillary and goes into interstitial space, and then

at the other end of the capillary bed the fluid goes back in, then it is returned, but not all of the

fluid goes back in, some of it is returned back to the heart via another circulatory system called

your lymphatic system. Here, the fluid leaves and goes into the corpora, and because the fluid

cannot exit back out because the penile vein is being compressed, then it just stays in that space.

That is the male reproductive system; now let us talk about the female reproductive

system. In the female reproductive system, we have ovaries and fallopian tubes connecting to

the uterus. The fallopian tube has regions; the section that surrounds the ovary is called the

fimbrea, meaning fingers, so the ovary is enveloped by the fallopian tube; the next region is the

ampula, and after that the infendipulum; the section that connects the fallopian tube to the uterus

is called the isthmus.

The fallopian tube, although it surrounds the ovary, they are not mechanically connected,

so it is possible for things to migrate up through the female reproductive tract and actually enter

into the abdominal cavity. Sometimes it is called PID, it is because the internal anatomy is

continuous with the outside world via the reproductive tract. During most times during the

reproductive cycle, there is a plug of mucus that covers the outside of the cervix to stop anything

from entering into the uterus.

The sections of the uterus are as such: the upper part of the uterus is called the fundus, the

larger part is called the body, and the part that connects with the vagina is the cervix. The uterus

has three layers; the innermost layer is the endometrium, but most of the uterus is a muscle, the

myometrium, and then the outer part is a membrane called the epimetrium. The myometrium

will permit the uterus to contract and ultimately expel the fetus; the endometrium creates an

internal environment that is required for the earliest stages of embryological development.

The uterus is connected to the vagina via the cervix. The cervix has an opening, a canal,

through the middle of it, which opens into the uterus and opens into the vagina. These openings

are called os, an external os and an internal os. The external os, under most circumstances, is

covered by a thick layer of mucus; the cervix has mucus glands that make mucus to cover the

openings so things do not migrate into the reproductive tract, and that is why the cervix is so

vulnerable to cancers, because of its secretory cells. The cervix then opens into the vagina, and

the vagina is a complex organ; it has an inner mucosal layer which is continuous with the

immune system, because the vagina is open to the outside world, so the surface of the vagina is

populated by a flora of organisms, and the mucosal layer has immune cells in it to restrict

pathogenesis and organisms from invading the underlying tissues. Deep to the mucosa is a

muscle, muscularis, and the outer surface of the vagina is an adventitia, it is a membrane that

attaches it to all surrounding space, it does not just wall it off but also interlaces it with

everything around it.

In a female, prior to participation in sexual activity, the outer opening of the vagina, the

vaginal orifice, is partitioned by something called a hymen that restricts movement into that

space. Ultimately, that outer opening is breeched either mechanically due to other kinds of

activities or due to penetrative sex. These structures are all soft tissue, if the ovary was sitting

there by itself it would just slump over, so they have to be interlaced into the body, so there are

ligaments that tether all of these structures onto the abdominal wall. There is a broad ligament

and an ovarian ligament and they attach everything to the wall of the abdomen. Sometimes as

women age, the weight of the reproductive tract, due to gravity, will cause the uterus to slump

down and prolaps (enter) into the vagina, and if the prolaps is so significant it can actually

protrude out of the vaginal orifice.

We are not going to mention the external genitals, but I want to mention one other

reproductive component which is the breast. The human breast is a little bit different from other

organisms; the mammary tissue is concentrated in two circular regions. The mammary tissue is

on the outer surface of the pectoralis muscles. The mammary gland ducts all come together to

form a single common duct that exists out through the nipple, and the nipple is surrounded by a

pigmented area, the areola. In between the mammary glands are pads of adipose, and the whole

thing is overlade by skin. The physical dimension of the breast is not determined by the amount

of mammary glands, but instead by the dimensions of the adipose.

Now we are done with the anatomy and we can talk about gametogenesis, the process of

making gametes; then we can talk about fertilization. For males and females, the process of

gametogenesis includes all the same steps—what differs is when and how many. The basic

process involves a population of cells that are your stem cells, your progenerative cells, meaning

they can make copies of themselves or become something else. For a female, they are called

oogonia, and spermatogonia for a male. The progeneratives can either proliferate and make

copies or differentiate and become gametes. Once the progenerative cells differentiate, they

become primary cells, either primary oocytes or primary spermatocytes. The primary cells then

undergo meiosis and after meiosis I they become secondary cells, secondary oocytes or

secondary spermatocytes. Then the secondary cells undergo meiosis II to become gametes, this

happens for males and females at some point in their lives.

For men, it is happens from the time they reach sexual maturity until they die, all of these

processes are occurring. For females, the process that led up to the formation of their oocytes

happened prior to birth. All females have only primary oocytes in their ovaries that have started

meiosis I; they stopped in prophase I, in homologous chromosome pairs, the four chromatids.

Once sexual maturity is reached, one of these primary oocytes will finish meiosis I and start

meiosis II, and that is during the menstrual cycle. When a woman ovulates, she releases one

secondary oocyte; the only way that the secondary oocyte will finish meiosis is if fertilization

occurs. For women, meiosis I produces a secondary oocyte and a polar body, and meiosis II

produces the egg and the secondary polar body. Females really have three different stages of

oogenesis: what occurs prior to birth, what occurs during the menstrual cycle, and what occurs

after fertilization. The only way an egg can finish meiosis II is if it is fertilized, so if it does not

get fertilized it dies, and that is why the female oocyte only lives 24 hours after ovulation.

Let us talk about spermatogenesis and then oogenesis in more detail. Men have

spermatogonia, some of them are always proliferating because it takes a couple hundred million

every time ejaculation occurs, and some of them differentiate and become primary

spermatocytes. Four cells are produced in meiosis, so if a male needs 250 million sperm every

time he ejaculates, he would need 60 million of his spermatogonia to differentiate, right? That is

not true, because the spermatocytes go through mitosis and amplify their numbers. If there is

one, you end up with 64. Before meiosis starts, the primary spermatocytes will clone themselves

five times, and then they will start meiosis and go through meiosis I and become secondary

spermatocytes, then meiosis II and form spermatids, but they are not sperm yet.

The spermatids have to acquire the physical characteristics of a sperm, so they undergo

spermiogenesis, where they form a flagellum which ultimately allows them to swim, and then on

the anterior end they form an acrosome, which is a sac of proteolytic enzymes that are going to

allow them to get through the outer barriers of the egg.

Remember we mentioned there are sertoli cells surrounding each developing sperm, so

the last thing the sperm needs to do is to be released from the sertoli cell, and this is called

spermiation. So to make sperm, spermatogonia differentiate to become primary spermatocytes;

the primary spermatocytes clone themselves then undergo meiosis to produce spermatids, and

this process is called spermatocytogenesis. The spermatids undergo spermatogenesis to acquire

the characteristics of sperm and to become spermatozoa. To release spermatozoa from the sertoli

cell, they undergo spermiation.

Now you have spermatozoa and they are stored in the epididymus until they are needed.

This whole process is controlled hormonally; remember FSH and LH produced by the anterior

pituitary control the gonads, so FSH controls how many primary spermatocytes are going to be

made and LH acts on the leydig cells and causes them to form testosterone. Testosterone

controls how quickly the sperm are made, so high levels of testosterone is going to cause rapid

formation of spermatozoa and FSH increases the number of spermatozoa you make.

Let us talk about the production of oocytes now. Primary oogonia differentiate and

become primary oocytes, grow and become bigger. Then the primary oocytes undergo meiosis I,

producing the secondary oocyte and the first polar body; then the secondary polar body

undergoes meiosis II to produce the egg and the second polar body. Meiosis II can only happen

if fertilization occurs; meiosis I happens during the menstrual cycle, and the cells are still

growing throughout their entire lives, the growth does not stop.

Let us talk about the hormonal control of the production of eggs. It is really easy to

control the production of millions of something, because if your objective is to make as many as

you can, it is easy. If your objective is to produce only one thing, that is really hard to do at a

biological level, so the process involves three different body systems. We have the endocrine

system with the pituitary and hypothalamus, the ovary, and endometrium. In the ovary, a woman

is born with hundreds of thousands of follicles surrounding her oocytes. The oocytes will

systematically grow as the follicles mature, so you go from very immature follicles ultimately to

primary follicles, to secondary follicles, to the most mature follicle which is the graafian follicle.

The graafian follicle is the one that will release the egg, and after it releases the egg, the

follicle becomes a very large secretory structure called the corpus luteum. Inside of the ovary,

there is this systematic process of causing the follicles to mature, and once every 28 days or so,

one of the follicles fully matures and will release an egg into the fallopian tube. Once that

graafian follicle releases that egg, the graafian follicle will then become the corupus luteum.

This is all tightly hormonally controlled. As for the endometrium, the endometrium is going to

thicken and eventually become glandular and vascular. The growth of the endometrium and the

changing of its characteristics is also hormonally controlled.

The control of all of these processes results from hormones produced by the anterior

pituitary. Remember, the anterior pituitary is controlled by the hypothalamus. The

hypothalamus produces a releasing hormone, GnRH, which then controls the anterior pituitary.

This is all collectively referred to as the menstrual cycle. At the beginning of the menstrual

cycle, GnRH is released from the hypothalamus and causes FSH to be released, follicle

stimulating hormone. FSH then acts on the follicles and causes follicles to mature. The

maturing follicles produce estrogen. Estrogen does three things: it goes back and changes the

way that GnRH is being released, so instead of causing FSH to be released it causes LH to be

released, since you do not need FSH anymore—FSH causes follicles to mature, and we only

want one follicle to mature, not more than one. So as estrogen levels go up, estrogen will go

back and shut off the production of FSH, but because we still need LH, it also causes LH to be

produced by the anterior pituitary. So estrogen stops FSH and causes LH to be released. In

addition, at the same time, estrogen travels through the bloodstream and to the uterus and causes

proliferation of the endometrium, so the endometrium grows and thickens.

LH, luteinizing hormone, acts on the graafian follicle and causes ovulation, which is the

release of the egg, and causes the graafian follicle to become the corpus luteum. The corpus

luteum then produces progesterone and estrogen. Progesterone goes back and shuts off the

hypothalamus and the anterior pituitary, because we have an egg and do not need any more eggs.

Then progesterone and estrogen act on the endometrium to cause it to become secretory, form

glands, and become vascular to prepare for implantation. Now we have an ovulated egg and

endometrium prepared for implantation.

At this point, we now have an egg that is released, and we have an endometrium that is

prepared. If this were a timeline of the menstrual cycle, ovulation occurs in the middle of the

menstrual cycle. The first day of the menstrual cycle is menses, because you are shedding the

last egg’s endometrium, it did not use it, so coincident to the formation of the next egg, you are

shedding the previous egg’s endometrium, the endometrium that did not get used. So ovulation

is in the middle of the menstrual cycle, and 14 days after ovulation, if the egg does not get

fertilized, would be the next menstrual cycle. It is 14 days because the corpus luteum is

producing estrogen and progesterone to keep the endometrium alive, but the corpus luteum

begins to degenerate after about 7 days after ovulation, and two weeks after ovulation there is not

enough estrogen and progesterone anymore to keep the endometrium alive, so it is shed as

menses. In order to have implantation, you need estrogen and progesterone from the corpus

luteum, but the corpus luteum is going to die. If reproduction is going be successful, we need to

keep the corpus luteum alive, so we need another hormone that keeps the corpus luteum alive if

in fact we are going to successfully reproduce, called HCG which is provided by the embryo.

HCG keeps the corpus luteum alive during the first three months of pregnancy.

The stage of the menstrual cycle before ovulation is called the follicular stage, when the

follicles are maturing. Then once the follicle has matured, you have the luteal phase, when the

corpus luteum is dominant. Day 1 of the menstrual cycle, the first hormone that increases is

FSH, as FSH levels go up estrogen is being produced; as estrogen levels go up, LH is produced.

Then LH spikes about two days prior to ovulation. If a woman wanted to test whether she is

pregnant, a pregnancy test tests for HCG because it is the only unique hormone that would only

be there if the woman were pregnant. Besides LH being produced as estrogen levels go up, FSH

levels go down. As LH goes up, the corpus luteum is formed, which produces progesterone and

estrogen, so estrogen levels continue to go up and now progesterone levels begin to increase as

well. If there is HCG, i.e. the woman is pregnant, estrogen and progesterone will stay elevated;

if there is no HCG, estrogen and progesterone levels will drop and will eventually be too low to

support the endometrium and the endometrium will be shed, and the next menstrual cycle starts.

Now we have gametes, eggs and sperm. Now we need them to join together.

Fertilization involves two different cells, and each of those cells has different responsibilities.

For the sperm, the first thing the sperm need to do is become motile, they need to go from being

dormant to being able to swim. This process is a two step process that involves something called

capacitation, and as soon as the sperm start moving through the male’s system, their metabolic

activity starts to increase. The reason why they cannot swim is because they do not have enough

cellular energy to do so, so they need to increase their metabolic activity to produce enough

cellular energy, so they undergo a process as they move through the male’s system called

capacitation. Once they get into the female reproductive tract, they undergo maturation and

reach full metabolic activity and can now swim.

The sperm are now inside the female reproductive tract and do not know where to go, and

fortunately for the sperm the egg releases a chemical gradient called chemotaxis, and the sperm

follow the chemical gradient to where the egg is. Once the sperm get to the egg, the egg is not a

single cell sitting in the fallopian tube, the egg is surrounded by multiple layers, parts of the

graafian follicle that came along with the egg. The innermost layer of the egg is called the

vitelline membrane, and the layer surrounding the vitelline membrane is the zone of halusida;

surrounding the zone of halusida is the corona radiata. The sperm have to swim through these

outer layers, so it pushes itself through the corona radiata, but at some point it cannot get all the

way through. Remember, on the anterior end of the sperm is a sac of enzymes held within its

acrosome; the acrosome will burst open, called the acrosome reaction, releasing those enzymes,

so now it will break down all of the fibers in the outer layers around the egg, and the sperm will

be able to swim through and attach itself to the vitelline membrane. Once the sperm gets to the

vitelline membrane, its job is done, everything else is now the responsibility of the egg.

The egg has a couple responsibilities. First of all, we saw that the egg produces the

chemical gradient, participating in chemotaxis. Once the sperm gets there, the first thing the egg

has to do is prevent hybrid formation. Remember when we were talking about speciation, we

said that in order to keep gene pools separate, we need barriers to the formation of hybrids, so

we have prezygotic and postzygotic barriers. The egg participates in a prezygotic barrier: on the

vitelline membrane are sperm receptors and the sperm has to activate a sperm receptor in order

for fertilization to occur. If it is not the sperm of the appropriate species, then the sperm cannot

activate the sperm receptor and fertilization will not occur. Hybrid formation is prevented

because only the sperm of the appropriate species can activate the sperm receptor.

After we prevent the hybrid, because we are a diploid organism and at this point the

gametes are haploid, we need to make sure only one sperm fertilizes the egg, so we want to

prevent polyspermy. There are two things that happen: the first is called the cortical reaction,

and after that you have the zonal reaction. In the cortical reaction, the vitelline membrane

releases a kind of substance called cortical granules that make the vitelline membrane really hard

and destroys all the sperm receptors, so during the cortical reaction the sperm receptors are

destroyed. During the zonal reaction, the vitelline membrane moves up and away from the egg,

pulling with it all the other membranes, so now the only part of the egg that is in contact with the

vitelline membrane is the part of the egg where the first sperm was. Any other sperm are

separated from the egg so that they cannot fertilize the egg, so the zonal reaction lifts the

vitelline membrane and the zona pellucida away from the egg so that no sperm can come in

contact with the egg. Then once that happens, the egg is safe to complete fertilization.

Now the first thing the egg has to do is finish meiosis, then it goes out and gathers up the

nucleus of the sperm, brings it inside the egg, then the two nuclei are fused together to form a

single diploid nucleus, and that is called synkaryon. That is the first cell of the new human.

Once that happens, development starts.