CAUTION: HORMONES AT WORK: PART VIII: SEX

We live in a world made up of matter. Matter consists of atoms and molecules that follow the laws of nature. All life is made up of atoms and molecules that are organized into cells. Our body has trillions of them. Everyone knows that a human is either male or female and that new life comes about through sexual reproduction. And most people know that the nucleus in each human cell normally contains 23 pairs of chromosomes which together house the genetic material needed to produce the essential molecules for life. There are even some people who know that, in addition to providing 22 somatic chromosomes, the female egg always provides an X chromosome and the male sperm provides either an X or Y chromosome to make a female (XX) or a male (XY) human person respectively. But what most people do not know and appreciate is how the body controls whether it makes male or female parts and, after puberty, produces sperm or eggs respectively and is then able to perform sexually. Although a given person’s survival does not depend on being fertile and having sexual intercourse, we all know that without adequate sexual function human life would be impossible. The proof of this is that if every male and female in the world were to suddenly become infertile the human race would die out in about a hundred years. In other words, adequate sexual development, fertility and function is one of the keys to human life. But how does the body do it?

As noted in previous articles, one of the most important sets of molecules which work to give the body control is hormones. However, although hormones are involved in helping the body control its sexual development and fertility the moment to moment control needed during sexual intercourse is provided by the nervous system. After all, the time needed for glands and their hormones to react and take effect usually requires several minutes. But when, in particular, the male body is trying to perform sexually it must respond in a matter of seconds or else risk malfunction which can lead to impotence and ultimately infertility. Similar to gland cells, the nerve cells take control by sending out chemical messengers called neurohormones. Experience teaches that the nervous system can respond in a split second to what we encounter in life. Let’s first look at what is needed to control something and then where hormones fit into sexual development and fertility, and neurohormones into sexual intercourse, to keep the human race alive.

Control
To be able to control something requires having at least three different parts all working together in harmony. The first thing you need is a sensor to detect what needs to be controlled. If you have no way of being aware of what needs to be controlled how can you control it? The sensor is like the reconnaissance team that an army sends out to check on the whereabouts and activities of its enemy. Without this information the army would be working in the dark. The second thing you need to control something is an integrator which interprets the information from the sensors, makes decisions about what needs to be done, and then sends out orders. If you don’t understand the information from the sensors and can’t make decisions about what should be done then what use are the sensors in the first place and how can you control something? The integrator is like army headquarters where the information from the reconnaissance team is analyzed, decisions are made about what needs to be done and orders are sent out. Without army headquarters there would be no coordinated action in the field. The third thing you need to control something is an effector which receives the orders from the integrator and does something. If you have a sensor to detect what needs to be controlled and an integrator to know what needs to be done, but not an effector to do it, then what’s the use of having the first two and how can anything be controlled? The effector is like the soldiers, who at the orders received from headquarters go and do what needs to be done. Without soldiers there is no army and the battle is already lost.

Hormones are protein molecules that are sent out by gland cells into the blood to help regulate specific functions of the body. They usually take several minutes to take effect. Nerve cells can transmit messages much faster than gland cells, literally in a split second or two. Just like gland cells they release different chemicals, called neurohormones, that stimulate or inhibit muscles, glands or other nerve cells. The hormones sent out by the gland cells, and the neurohormones sent out by the nerve cells, are chemical messengers which are just like the orders sent out by army headquarters. In particular, specialized gland and nerve cells, located in strategic places in the body, have sensors on their surface to detect certain chemicals and physical activity (like what is related to sexual development, fertility and sexual intercourse). In other words, the glands of the body and the nervous system have their own reconnaissance team that can detect a specific chemical or physical sign which the body must control to keep the human race alive. The information that the glands receive is analyzed and directly affects their function. In addition, the data from the special nerve cells is sent rapidly to the brain and spinal cord where it is analyzed and directly affects the nerve messages they send out. Together, the glands and the nerve cells in the brain and spinal cord act as the integrator, just like army headquarters, to send out orders to direct the activities in the field. These actions, done at a distance from the sensors and the central nervous system, are designed to achieve a specific goal; the control of a specific function and physical action (like sexual development, fertility and sexual intercourse) so the body can work to keep the human race alive. The hormones the glands send out affect specific target organs and pass on the new orders. Likewise, the specific messages from the brain and spinal cord travel along specific nerves which release specific neurohormones in the specific target organs to pass on their orders as well. The cells in the specific organs that receive the messages from the glands and the central nervous system act as the effector, which, like the soldiers in the field, receive the orders and perform a specific action. This effect, done at the direction of the integrator, helps to control a specific function or physical activity (like sexual development, fertility and sexual intercourse).

However, army headquarters must send out different orders to different soldiers telling them to do different things. So too, the body’s different nerve and gland cells must send out different messages to different target cells to get different things done. And just as the soldiers can’t take just any message or do whatever they want, the target cells must respond to the right message and do the right thing, otherwise the body wouldn’t be able to control anything. The way the body ensures that the right target cells receive the right orders so they can do the right thing is for them to have specific receptors. The receptors in the target cells are proteins with a special shape that allow them to attach to specific molecules when they come in contact with them. Think of it like a key fitting into a lock, or tuning your radio or television to a specific station. When the neurohormone or hormone attaches to its specific receptor this signals the target cell to do something. And what the target cell does directly affects the specific function (like sexual development or fertility) and physical activity (like sexual intercourse) that the body is trying to control.

First, we’ll look at the structures each sex must have to perform properly and what must take place for new human life to come about, and then, how the body decides whether it will make male or female parts. Following this we’ll look at what happens during puberty to bring about fertility. And finally, we’ll look at the specific tasks each sex must be able to perform to accomplish human reproduction and in particular, what can go wrong to cause permanent infertility. I suggest that you be prepared to exercise your wonder as you never have before! For, contrary to popular opinion, being a male requires much more than just having a Y chromosome, being fertile requires much more than just having testes or ovaries, and being able to perform sexually requires the male to have much more than just a penis.

Sex
The word “sex” comes from the Latin “secare” which means “to divide or separate”. Each of the 23 pairs of human chromosomes are separated from each other and are placed in gametes called male sperm and female eggs. Human reproduction requires that the 23 chromosomes in the sperm that are separated from the 23 chromosomes in the egg be joined together into a new human being. The natural way this takes place is through sexual intercourse. This involves the male depositing sperm from his penis deep inside the female’s vagina so they can travel through the cervix into the body of her uterus and have a chance to join up with the egg. To accomplish this task the male is equipped with testes, which produce sperm, and a genital duct system (epididymis, vas deferens and seminal vesicle) and external genitalia (penis, scrotum and prostate gland) which together help move the sperm out of his body. http://www.mayoclinic.com/health/medical/IM02745 The female is equipped with external genitalia (labia, clitoris and lower vagina) and a genital duct system (upper vagina, uterus and fallopian tubes) which help to guide the sperm toward an egg that has been released from one of her ovaries. http://www.mayoclinic.com/health/medical/IM01236 The sperm and egg usually meet in one of the fallopian tubes where the one-celled zygote (new human life) forms. The zygote quickly becomes an embryo which migrates from the fallopian tube into the body of the uterus and implants in its lining (endometrium) which allows it to grow and develop into a new born baby that exits into the world about nine months later.

In The Beginning: Sexual Differentiation
For the first several weeks of life the human embryo is asexual because the gonads have not yet declared themselves to be either testes or ovaries. Human embryology teaches that the undifferentiated gonads are destined to become ovaries by default unless acted upon by a molecule called the “Testis Determining Factor” (TDF). The genetic information needed to produce TDF is located on the “Sex Determining Region of the Y chromosome” (SRY). The testes produce testosterone and the ovaries produce estrogen. The body uses many different enzymes, encoded on several different somatic chromosomes, to produce both of these sex hormones from cholesterol. By telling the primordial gonads to become testes, the TDF on the SRY is therefore the master switch that makes the body go down the male track rather than the female one instead.

Each human embryo begins life with two different undeveloped genital duct systems, the Wolffian ducts and the Mullerian ducts. If the gonads do not become testes and produce testosterone, then the Wolffian ducts degenerate and disappear and the Mullerian ducts develop into the female genital duct system (upper vagina, uterus and fallopian tubes). However, if the gonads become testes, the testosterone they produce attaches to specific androgen receptors which are encoded on the X sex chromosome and directs the Wolffian ducts to develop into the male genital duct system (epididymis, vas deferens and seminal vesicle). In addition to testosterone the testes also produce another molecule called “Anti-Mullerian Hormone” (AMH) which is encoded on the 19th chromosome. AMH attaches to specific AMH receptors, which are encoded on the 12th chromosome, and directs the Mullerian duct cells to degenerate and disappear. This is very important because if both the Wolffian and Mullerian ducts develop this renders the person infertile. Here again we see that the human embryo is destined to become female unless acted upon by specific molecules, in this case, testosterone and AMH, with the help of the androgen and AMH receptors as well.

The external genitalia develop from the urogenital sinus, swellings, folds and tubercle. If the gonads do not become testes and produce testosterone these automatically develop into the female external genitalia (labia, clitoris and lower vagina). However, for this tissue to become the male external genitalia requires much more stimulation of the androgen receptor than testosterone can provide. The cells in these tissues use an enzyme, encoded on the 2nd chromosome to convert testosterone into dihydrotestosterone (DHT) which is a stronger stimulator of the androgen receptor. When DHT attaches to the androgen receptors in these tissues it makes them develop into the penis, the scrotum and the prostate gland. Again we see that the human embryo is destined to develop into a female unless acted upon by specific molecules, in this case DHT, with the help of the androgen receptor.

In summary, the human embryo is destined to become female by default unless specific molecules (e,g. TDF, testosterone, AMH, DHT), attaching to specific receptors (androgen receptor, AMH receptor), makes it become a normal male instead. The Y chromosome contains the genetic material needed to start the embryo down the road to masculinity (SRY). But this, in itself, is not enough to bring about a baby boy with proper male sexual parts. In fact, several other somatic chromosomes, and even the X chromosome, are needed because they contain the critical genetic material to bring about a normal human male (enzymes to form testosterone and convert it to DHT, androgen receptor, AMH and AMH receptor).

Puberty: Sexual Maturation and Fertility
Experience teaches that although humans are sexually differentiated as male or female at birth, they are, as yet, unable to reproduce. Most children begin to show signs of their sexual development to come by the end of the first decade. Over the following several years they will undergo sexual and bodily development in a process called puberty. Puberty involves a constellation of physiological changes in the body that, not only enables a person to reproduce, but also prepares them for their natural role in the family.

The hypothalamus and the pituitary work together to control many different vital hormones in the body, including the sex hormones; testosterone and estrogen. They also control whether a man can produce sperm and a woman can produce eggs. The hypothalamus sends out Gonadtropin-releasing Hormone (GnRH) which attaches to specific receptors on specific cells of the pituitary. The GnRH stimulates these cells to produce and secrete the gonadotropin hormones, Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH). It is FSH and LH that travel in the blood and attach to specific receptors in the testes of sexually mature males to produce testosterone and sperm, and the ovaries of sexually mature females to produce estrogen and progesterone, and allow a mature egg to move from the ovary toward the fallopian tube in a process called ovulation.

The function of both the hypothalamus and the pituitary is directly affected by what their sensors detect regarding the blood level of the sex hormones. In general, this type of control is called “feedback inhibition” in that the blood level of the sex hormone feeds back on the hypothalamic and pituitary cells and if it rises above a certain set point, then this inhibits their function. In other words, the hypothalamus and the pituitary send out a certain amount of hormone to maintain a certain blood level of the sex hormones, but if this level rises too high, they reduce their output and if it drops below the set point they increase their output.

It appears that from the time of birth leading up to puberty, the hypothalamus and the pituitary are very sensitive to the feedback inhibition of the sex hormones. This means that during the first several years of life the hypothalamus and the pituitary seem to be pre-set to secrete very low levels of GnRH, and FSH and LH, respectively. Consequently, this results in there being very low blood levels of, testosterone in young boys, and estrogen in young girls. It seems that the undifferentiated tissues in the embryo are sensitive enough to these very low levels of sex hormones to still differentiate into the male or female genital duct systems and external genitalia. However, medical experience teaches that these differentiated tissues require much higher levels of sex hormones to develop further so that a person is capable of participating in sexual reproduction.

What actually triggers the beginning of puberty is, as yet, poorly understood. However, what is known to happen is that the hypothalamus and the pituitary start to become progressively less sensitive to the blood level of the sex hormones. This gradually diminishing feedback inhibition of the sex hormones on the hypothalamus and pituitary results in them slowly increasing their output of GnRH and the gonadotropins (FSH and LH). The increasing amounts of FSH and LH has a positive effect on the testes of males and the ovaries of females, causing an increase in the production of testosterone and estrogen respectively. The marked increase in the blood levels of FSH, LH and testosterone causes boys to have an increased distribution and coarsening of hair, enlargement of the vocal cords causing a deepening of the voice, a significant linear growth spurt and the development of the musculoskeletal system, and also an increase in the size of the penis and testes with the capacity to produce sperm. And the marked increase in the blood levels of FSH, LH and estrogen causes girls to have an increase in mainly pubic and axillary hair, breast development, a significant linear growth spurt and the development of the musculoskeletal system, and enlargement of the external genitalia and also gives their ovaries the capacity for egg development and release in a process called ovulation. It is ovulation that allows the egg to migrate from the ovary and into the fallopian tube where it can meet up with the sperm to form new human life.

In summary, the body is able to, not only control whether a person will form male or female parts, but also, several years later, make these parts mature so the person is fertile and can participate in sexual intercourse. But how does it do it? Recall, the first thing you need to control something is a sensor to detect what needs to be controlled. The hypothalamus and the pituitary have sensors that can detect the blood levels of the sex hormones, testosterone and estrogen. Recall, the second thing you need to control something is an integrator that can take the data it receives from the sensors, compare it with a standard, and then decide what must be done. From the time the embryo becomes male or female until the beginning of puberty the hypothalamus and the pituitary are very sensitive to the feedback inhibition of the sex hormones. In other words, at this time of life, the hypothalamus and the pituitary respond to the very low blood levels of sex hormones by limiting the output of their respective hormones to keep the levels of testosterone in the male and estrogen in the female very low. Then, several years later, as puberty begins and continues through to adulthood, the hypothalamus and the pituitary become less sensitive to this feedback inhibition resulting in much higher blood levels of testosterone in the male and estrogen in the female. Recall, the third and final thing you need to control something is an effector that can do something about the situation. From the time an embryo becomes male until the beginning of puberty he develops a male genital duct system and male external genitalia due to testosterone and DHT having attached to the androgen receptors of his primordial genital tissues. During puberty, with a significant increase in the blood level of testosterone a boy develops into a man and is capable of sexual reproduction. From the time an embryo becomes female until the beginning of puberty she develops a female genital duct system and external genitalia due to the absence of testosterone, AMH and DHT. During puberty, with a significant increase in the blood level of estrogen, a girl becomes a woman and is capable of sexual reproduction.

Parenthood: Sexual Intercourse, Fertilization, Implantation and Gestation
Once the sexual organs have matured so the male can produce sperm and the female can release an egg into the fallopian tube, all that is needed for new human life to come about is for them to join together to form a zygote. The natural way that human reproduction occurs is by the male and female physically coming together in sexual intercourse. This very intimate physical union requires the man to insert his erect penis into the naturally lubricated vagina of the woman and ejaculate semen (fluid containing sperm) near the cervical opening of the uterus. Over the next several hours, aided by the cervical mucus, the sperm will use their flagella to swim through the body of the uterus toward the fallopian tubes. If one of the woman’s ovaries has released an egg around that time then one of the sperm may be able to penetrate its outer shell to form a zygote in a process called fertilization. Over the next several hours the zygote will develop into an embryo which over the next several days will migrate into the uterus and implant in its inner lining (endometrium). Once implantation takes place the embryo continues to develop and grow into the fetus in a process called gestation and then exits the mother’s body about nine months later as a new born baby.

Parenthood: Male Sexual Function And What Can Go Wrong
From the above it is evident that the male’s fertility is mainly dependent on two tasks; (1) producing enough healthy sperm, and (2) being able to deposit them deep inside the vagina of the female.

The first task of the male (producing enough healthy sperm) is mainly accomplished by the testes. This function is dependent on having enough of the gonadotropins (LH and FSH) and testosterone along with their specific receptors. The sperm produced in the testes is combined with nutrient fluids from the seminal vesicles and the prostate gland to form semen. During sexual intercourse the semen is released from the erect penis into the woman’s vagina. The normal amount of semen usually needed for adequate fertility is at least 2 mL and the concentration of sperm should generally be greater than 20 million per mL. In addition, the appearance of the sperm (morphology) and their ability to move well (motility) are very important factors that affect fertility as well. For, if most of the sperm are structurally abnormal and/or are unable to swim vigorously, then reproduction is unlikely to take place.

There are several conditions that can cause inadequate counts, or even the total absence, of healthy sperm. One category involves inborn errors such as genetic disorders, in which the testes do not develop and mature properly, and metabolic disorders, which affect the production of testosterone. The other category involves acquired conditions such as emotional stress, smoking, alcohol and other substance abuse, viral and sexually transmitted infections, vitamin and mineral deficiencies, toxins, radiation, trauma, surgery, medications, diabetes, hypothalamic and pituitary conditions resulting in low levels of testosterone, thyroid disease, aging, obesity and anti-sperm antibodies. In addition, the testes are housed in the scrotum, away from the inner aspect of the body, because proper sperm production requires that the temperature of the testes be lower than the body’s core temperature. Therefore, overheating of the testes, such as in men whose testes never descended into the scrotum (cryptorchidism), or who frequent saunas or wear tight underwear, can also result in male infertility as well.

The second task of the male, potency (being able to deposit the sperm deep inside the vagina of the female), requires the man to have a firm enough penile erection and be able to ejaculate semen into the vagina. Penile erection is achieved by hydraulic pressure. Running the length of the penis, surrounding the urethra, above and on each side, are the corpus spongiosa and the corpus cavernosa. These tube-shaped venous chambers are surrounded by strong fibrous tissue. http://men.webmd.com/picture-of-the-penis When properly stimulated the nerves in the pelvic region send out messages that cause an increase in arterial blood flow into these chambers while at the same time greatly reducing the venous outflow. This causes the blood to collect within these chambers resulting in penile erection. Sex-related thoughts and stimulation of the sensory nerves in the penis and pelvic region turn on the parasympathetic nervous system which sends out a neurohormone called acetylcholine. The acetylcholine attaches to specific receptors on the blood vessels in the penis to cause the erection. With continued stimulation the sympathetic nervous system turns on and sends out a neurohormone called norepinephrine. The norepinephrine attaches to specific receptors on the associated pelvic muscles resulting in coordinated contraction and ejaculation of the semen from the penis which is usually accompanied by the pleasurable sensation of orgasm. As sympathetic nerve stimulation brings on climax and ejaculation to complete the sexual act the parasympathetic stimulation that caused the erection in the first place turns off and the penis becomes flaccid soon afterwards.

As noted above, adequate penile erection resulting in ejaculation is a well coordinated process that involves having normal pelvic blood flow and nerve function. If there are significant problems with the neurovascular function of the pelvic region then erectile dysfunction (impotence) is likely to take place. Fatigue and emotional causes of erectile dysfunction are usually temporary, but there are many conditions that can lead to permanent impotence. Atherosclerosis (hardening of the arteries), usually related to smoking, hypertension, diabetes and hyperlipidemia, can cause peripheral vascular disease and limit the blood flow to the penis. Moreover other conditions associated with vascular problems like coronary artery disease, congestive heart failure and kidney disease can all lead to impotence as well. In particular, diabetes not only affects blood flow but also nerve function as well and therefore diabetic men are particularly at risk for impotence. Other conditions that can not uncommonly lead to nerve malfunction and impotence include alcohol and other substance abuse, medications, anemia, testicular dysfunction, spinal cord or pelvic injury and neurodegenerative conditions such as Multiple Sclerosis, Parkinson’s Disease and stroke. Although most of the conditions that can lead to impotence affect vascular and/or nerve function, there is one that is related to a defect in the fibrous structure of the penis itself. Peyronie’s disease is a condition in which scar tissue, from plaque formation, forms within the walls of the penis resulting in a deformed and often painful erection. This usually makes sexual intercourse not only very uncomfortable but often impossible.

In summary, the two main tasks of male fertility (producing enough sperm and depositing them deep inside the vagina of the female) requires much more than just having male sexual organs. He must be able to produce enough healthy and vigorous sperm, which is dependent on him having, not only properly working testes, but the right amount of hormones and properly working receptors as well. In addition, it isn’t enough that he has a properly built male internal genital duct system and external genitalia. He must also have proper neurovascular function in the pelvis, which involves the neurohormones acetylcholine and norepinephrine and their specific receptors, to achieve enough of an erection to penetrate the vagina and ejaculate his semen toward the cervical opening.

Parenthood: Female Sexual Function And What Can Go Wrong
From the above it is evident that the female’s fertility is mainly dependent on three tasks; (1) developing and releasing an egg from the ovary, (2) getting the egg to enter the fallopian tube while assisting the sperm to reach it for fertilization, and (3) providing nutritional support for the developing new human life once it implants in the endometrial lining of the uterus.

All women have their total complement of immature eggs (ova) in their ovaries at birth. These eggs are contained in sacs with surrounding support tissue that are called follicles. The first task of the female (developing and releasing an egg from the ovary) is dependent on the gonadotropins (FSH and LH) and estrogen. At the beginning of a woman’s menstrual cycle the blood level of estrogen is low. This tells the hypothalamus to secrete more GnRH and the pituitary more FSH and LH. In particular, by attaching to specific receptors the rise in FSH stimulates some of the follicles in the ovaries to mature and make estrogen as well. At this point the ovary is said to be in the follicular phase. Throughout this phase the cells in the maturing follicles form more receptors for both FSH and estrogen which results in a positive feedback that makes the follicles even more sensitive to FSH and estrogen. This increased sensitivity enables them to produce more and more estrogen and causes the eggs to mature further. The dominant follicle that will ultimately release an egg (ovum) at ovulation is the one which has been able to produce the most FSH and estrogen receptors. During this phase, as the estrogen level rises higher and higher. something very surprising takes place in the pituitary. Recall, prior to puberty the release of FSH and LH is normally inhibited by a rising estrogen level. This in fact is how the body is able to keep control of its estrogen level. However, as the ovary nears the end of the follicular phase, when the level of estrogen is rising higher and higher, this actually stimulates the pituitary to suddenly release more LH (and to a lesser degree FSH as well) in what is called the LH surge. This actually represents a positive feedback which as yet is still poorly understood. The LH surge is absolutely necessary for the dominant follicle to release the egg from the ovary so it can migrate toward the fallopian tube and have a chance of meeting up with a sperm. This process is called ovulation.

There are several conditions that can result in the ovaries not being able to send out an egg toward the fallopian tube (anovulation). One category involves inborn errors which results in the ovaries not developing and maturing properly. The vast majority however are acquired disorders which usually are intermittent and with medical intervention can be resolved. Consistent monthly ovulation is dependent on the delicate and complex interplay of the hypothalamus, the pituitary and the ovaries. Disruption of this hormonal balance by chronic emotional stress, malnutrition, significant fluctuations in weight, serious or recurrent illness and excessive physical exercise are some of the commoner reasons for anovulation. Another not uncommon condition is polycystic ovary syndrome (PCOS). PCOS occurs due to the inappropriate negative feedback of the sex hormones on the pituitary gland. This causes a relatively low level of FSH which limits the cyclical development of the follicles in the ovaries so that a dominant one is not able to be released in ovulation. Also, there are numerous different glandular disorders, such as ones that affect the thyroid, the adrenals or the pituitary, which can lead to anovulation as well. Finally, it must be remembered that each woman begins her life with a full complement of egg follicles in her ovaries. Since, after puberty, during each month several follicles mature and vie for ovulation, this means that there are that many less follicles available for ovulation and estrogen production in the future. A woman’s fertility therefore eventually runs out and with it she no longer ovulates or has menstrual periods and has very low levels of estrogen. This is called menopause and usually takes place after thirty to forty years of menstruating.

If the female has had sexual intercourse around the time she has ovulated then her second task comes into play (getting the egg to enter the fallopian tube while assisting the sperm to reach it for fertilization). By attaching to specific receptors, the high levels of estrogen prior to ovulation makes the cells in the cervical opening of the uterus secrete lots of watery mucus. This watery mucus assists the sperm as they swim up through the body of the uterus to the fallopian tubes. At the same time, the high levels of estrogen also causes the fallopian tubes to increase the movement of their cilia (small hair-like projections) and muscle contraction in an effort to try to coax the egg to enter it. Once inside the fallopian tube the egg is swept along toward the body of the uterus by ciliary action and muscle contraction. It is here, within the relatively confined space of the fallopian tube, that the sperm usually meet up with the egg and fertilization takes place. The resulting zygote is then also swept along the fallopian tube into the body of the uterus on its way to implantation.

Some of the commoner causes of female infertility involve disorders of the fallopian tubes. Sexually transmitted diseases, like gonorrhea and chlamydia, cause pelvic infections which results in damage to the fallopian tubes and abnormal function. This causes them to either not be able to capture the egg, let the egg and sperm meet, or let the zygote pass through to the body of the uterus. Another not uncommon cause of fallopian tube malfunction, resulting in female infertility is a condition called endometriosis. This disorder involves the growth of tissue from the lining of the uterus (endometrium) in abnormal places, such as around the fallopian tubes and the ovaries. The presence of this abnormally-placed endometrial tissue causes obstruction and damage of the fallopian tubes resulting in malfunction. Recall, the second task of the female involves not only the fallopian tubes but also the cervical opening of the uterus where the sperm enter on their way to trying to fertilize the egg. Sexually transmitted diseases, like gonorrhea and chlamydia, can also cause inflammation and scarring of the cervix. This can lead to narrowing of the cervical canal and abnormal mucus production both of which can prevent the sperm from moving up into the uterus. In addition, certain hormone problems can cause the cervix to not produce the right amount and/or kind of mucus to adequately help the sperm move into the uterus.

If a sperm is able to fertilize an egg in the fallopian tube and the resulting zygote is able to move into the body of the uterus then the third task of the female becomes necessary (providing nutritional support for the developing new human life once it implants in the endometrial lining of the uterus). The increasing amounts of estrogen that the ovary releases prior to ovulation attaches to specific receptors in the endometrial lining of the uterus and signals it to proliferate. This causes the endometrial lining to grow and develop resulting in it secreting large amounts of clear mucus which aids the sperm in their struggle to reach the fallopian tubes. After ovulation the remaining cells of the dominant follicle become the corpus luteum (yellow body) and begin to form more LH receptors on their cell membranes. The predominance of LH receptors on these cells results in the production of mostly progesterone, and to a lesser extent, estrogen as well, from continued FSH stimulation. Progesterone attaches to specific receptors on the endometrial lining and signals them to proliferate further and to secrete a thicker and more nutrient-rich mucus in preparation for the implantation of the embryo. The corpus luteum normally has a lifespan of only about 10 - 14 days at which time a precipitous drop in the production of estrogen and progesterone takes place. This sudden drop in the levels of sex hormones results in the endometrial lining no longer being supported and it degenerates and dies. The endometrial tissue is then shed, with blood, out of the uterus and into the vagina and from there out of the woman’s body in a menstrual period. However, if pregnancy does take place the embryo produces an hormone called “human Chorionic Gonadotropin” (hCG) which acts like LH and is able to keep the corpus luteum alive and functioning until the placenta forms and takes over. From here on gestation takes place whereby the embryo develops into a fetus and continues to grow and develop within the uterus until it comes out into the world as newborn baby several months later.

For a healthy pregnancy to continue the embryo must implant on the lush endometrial lining of the uterus. The presence of uterine defects, such as abnormal shape, a dividing wall (septum), benign muscle tumors (fibroids), and abnormal mucosal growths (polyps) can interfere with either implantation or continued gestation resulting in infertility. If the corpus luteum does not secrete enough progesterone for an adequate amount of time the endometrial lining will not be prepared to properly nurture the embryo. Finally, one other rare cause of luteal phase insufficiency is the complete absence of progesterone receptors on the gland cells of the endometrium. Without these specific receptors the progesterone secreted by the corpus luteum cannot stimulate the endometrium and it cannot grow and develop properly and the uterine lining will be unable to perform the third task of female fertility.

Summary
In summary, human reproduction involves not only having the right tissues and organs in place, but also having them working together in a well coordinated fashion. The male cannot be fertile unless he produces enough healthy sperm and can participate properly in sexual intercourse with the female. The female cannot be fertile unless at least one of her ovaries can release an egg, her fallopian tube can capture it and move it towards the sperm that have entered the uterus through the cervix, and then provide a supportive haven for the implantation and gestation of new human life. These all require, not only having the right tissues and organs in place, but also having the right amount of hormones and receptors that respond in the right way and at the right time as well. Any one permanent abnormality that leads to any one chronic malfunction involving either male or female fertility is likely to make human reproduction impossible. It is evident that the continuation of human life is dependent on numerous different complex but interdependent processes each of which can easily go awry.

Points to Ponder
Most simple one-celled organisms form offspring through asexual reproduction. This means that their genetic material does not separate and the new life they produce is genetically identical to the original. In contrast, most multi-cellular organisms, like insects, amphibians, reptiles, birds and mammals, form offspring in a much more complex way called sexual reproduction. This means they form gametes, like male sperm and female eggs, each of which contain only half of the full complement of their genetic material. When the sperm of a male and the egg of a female join up with each other their chromosomes come together to form the full complement of genetic material needed for new life. The chromosomal content of this new human is genetically distinct from its father and mother. The three things needed for a person to be able to reproduce are; (1) be either a male or female, (2) be able to produce enough sperm or eggs, and (3) be able to participate in sexual intercourse. Notwithstanding how the undeveloped genital tissues came into being in the first place, since the human embryo becomes female by default unless it is acted upon by several chemical factors, and it is the male that must enter the vagina and ejaculate semen, let’s look at what is required just for male fertility.

Whereas nothing else needs to happen for the human embryo to become a normal female, just to become a normal male instead requires (1) the Testis Determining Factor (TDF) which is located on the Sex Determining Region of the Y chromosome (SRY), (2) the enzymes needed to convert cholesterol into testosterone and dihydrotestosterone (DHT), (3) the androgen receptor, and the presence of (4) Anti-Mullerian Hormone (AMH) and (5) the AMH receptor. And like for the female, who needs (6) Gonadotropin releasing hormone (GnRH) from the hypothalamus and (7) its specific receptor on the pituitary, in addition to (8) Follicle Stimulating Hormone (FSH) and (9) Luteinizing Hormone (LH) and their specific receptors (10 & 11), the male also needs all of these for his fertility as well. Finally, male fertility is also dependent on, not only having enough testosterone and properly working androgen receptors but also normal pelvic neurovascular function to allow for a firm enough erection to enter deep into the vagina and to be able ejaculate semen toward the cervical opening of the uterus. This involves both the parasympathetic and sympathetic nervous systems with their respective neurohormones (12) acetylcholine and (13) norepinephrine along with their specific receptors (14) & (15) as well. If any one of these fifteen or more parts were to be missing, or not working properly, the whole system would fail and the male part of human reproduction would be impossible. Dr. Michael Behe has called a system where the absence of any one part renders it useless as being irreducibly complex. The numerous systems needed for male fertility demonstrates irreducible complexity. One must then wonder how an irreducibly complex system with so many vital parts could have come into existence while remaining functional every step along the way? Does it make sense that this system could have come about one step at a time? The idea is totally absurd. They must have all come together as a system to perform a function to keep the human race alive. For, when it comes to human reproduction, becoming a male requires much more than just having a Y chromosome, being fertile requires much more than just having testes or ovaries, and being able to adequately perform sexually requires the male to have much more than just a penis.

The last several articles have explained the organization and importance of different tissues and proteins each of which is necessary for body survival. For example, the cardiovascular and respiratory systems, working with hemoglobin, makes sure there is enough oxygen in the tissues. And the gastrointestinal system brings glucose into the body but requires the pancreas and the liver to control its availability through the secretion of insulin and glucagon. In contrast, this chapter has described the organization and function of the tissues, organs and proteins needed for sexual reproduction, none of which is absolutely necessary for a given person’s survival. From the time of birth to puberty a person is able to survive quite well despite having minimal levels of sex hormones, immature genitals and not being able to reproduce. Yet, sexual intercourse between a mature male and mature female must take place for new human life to come about. Herein lies a further conundrum that needs to be explained by Science. The previous articles have shown that it is very difficult to understand how each of the many different organ and hormonal systems needed for life could have come into existence while the body remained viable each step along the way. But the information in this chapter on human reproduction shows that, in addition, one must now explain the simultaneous development of the complementary sexual organs and hormonal systems required to reproduce life. In other words, it is not enough to simply explain the development of males or females at some time or other. One must explain the development of both males and females at the exact same time since neither one is of any use for survival without the other. What this means is that although there may be similar systems for sexual reproduction in similar or even divergent organisms this does not in and of itself explain how they came into being never mind how they functioned adequately each step along the way of their development to allow for reproduction and species survival. Many moderns claim that it was “nature” that made it happen through macroevolution, a process which by definition is supposed to be blind to where it is going. I once had a biology teacher say this to me and I advised him that he was making “nature” the intelligent designer of life.

Also, besides being irreducibly complex the systems involved in male and female fertility demonstrate a natural survival capacity since by their combined functions they enable a given species to reproduce within the laws of nature. In other words, besides the tissue and organs needed, not just any amount of the hormones involved or the sensitivities of the receptors needed to respond properly will do. It has to be the right amount to get the job done. And since natural forces like inertia, friction and gravity would tend to prevent the sperm from traveling up through the uterus to the egg and the zygote from migrating into the body of the uterus, the organic parts involved in human sexual reproduction must be able to overcome the laws of nature to make new human life possible. So, the tissues, organs and proteins needed for human reproduction demonstrate natural survival capacity by making it possible for new human to come about despite the forces of nature they are up against.

Experience teaches that an electrical appliance must be connected to an energy source to work. At the end of the electric cord of all appliances is a plug. The plug consists of prongs, or pins, made of metal, which make them solid enough while at the same time being good conductors of electricity. In fact, the plug is often referred to as the male component of the electrical connection. The plug has to be firm enough and have the right shape to fit into the electrical socket to connect up with the electrical energy that will allow it to work. Men with erectile dysfunction, who cannot maintain a firm enough erection, and those with Peyronie's disease, who have abnormally shaped erections, are like electrical appliances with defective plugs. Without a properly working plug the electrical appliance is useless to its owner. The electrical receptacle, also called the female component of the electrical connection, must not only have a complementary shape for the plug, but also be properly connected to the power supply. A woman who has a physical or metabolic defect that makes her infertile is like an electrical socket that short-circuits and renders both the appliance and human reproduction as ineffective.

The laws of nature have put up many obstacles to prevent life from existing. Just as a car can die from not having enough gas for energy, or oil for seizing parts, or anti-freeze for engine overheating, so too, all physicians know that there are many different pathways to death. If you really want to begin to understand how life came into existence, you first have to understand how easily it can become non-existent. Did life really come about solely by random chemicals coming together to form cells, then simple organisms, and then complex ones like us? In other words, without “a mind at work” to make it happen?

Do you think the electric plugs for appliances and the electrical receptacles they plug into came into being and are able to work properly solely by the random forces of nature?

No, when it comes to the origin of life it seems to me that Science still has a lot of explaining to do!


Be sure to catch all of the articles in Dr. Glicksman's series, "Beyond Irreducible Complexity."



Howard Glicksman M. D. graduated from the University of Toronto in 1978. He practiced primary care medicine for almost 25 yrs in Oakville, Ontario and Spring Hill, Florida. He now practices palliative medicine for a Hospice organization in his community. He has a special interest in how the ethos of our culture has been influenced by modern science’s understanding and promotion of what it means to be a human being.

Copyright 2014 Dr. Howard Glicksman. All rights reserved. International copyright secured.

June 2014