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In the Beginning: Male and Female

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Editor’s note: Physicians have a special place among the thinkers who have elaborated the argument for intelligent design. Perhaps that’s because, more than evolutionary biologists, they are familiar with the challenges of maintaining a functioning complex system, the human body. With that in mind, Evolution News is delighted to offer this series, “The Designed Body.” For the complete series, see here. Dr. Glicksman practices palliative medicine for a hospice organization.

the-designed-body4.jpgEveryone knows that a human being is either male or female. And most people know that the nucleus in each human cell normally contains 23 pairs of chromosomes which house the genetic material needed to produce the essential molecules for life. There are even some 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.

But what most people do not know or appreciate is how the body decides whether to make male or female parts. Although a given person’s survival does not depend on having the right parts for reproduction, we all know that without adequate sexual function human life would be impossible. Moreover, as difficult as it may be for evolutionary biologists to explain the development of the different organ systems and the body’s ability to control them to survive within the laws of nature, because of how human reproduction takes place, they must also explain the simultaneous development of both males and females since neither is of any use for survival without the other. Let’s look at the structures each sex must have to reproduce and how the body decides which ones to develop.

The word sex comes from the Latin secare which means to separate or divide. Each of the 23 pairs of human chromosomes are separated from each other and placed within gametes called male sperm and female eggs. Human reproduction requires that the 23 chromosomes in the sperm be joined to the 23 chromosomes in the egg to form a new human being. The natural way this takes place is through sexual intercourse. This involves the male depositing sperm from his penis into the female’s vagina so they can travel through the cervix into the body of her uterus and one of them can join up with an 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) to help move the sperm from the testes out of his body. The female is equipped with external genitalia (labia, clitoris, and lower vagina) and a genital duct system (upper vagina, uterus, and fallopian tubes) to help guide the sperm toward an egg that has been released from one of her ovaries. The sperm and egg usually meet in one of the fallopian tubes of the uterus where the newly formed one-celled zygote forms a new human life. The zygote soon starts to divide, becoming an embryo which migrates into the body of the uterus and implants in its endometrial lining, allowing it to grow and develop into a newborn baby that exits about nine months later.

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). So this explains why a male must have a Y chromosome…or does it? Nature can sometimes play tricks and a translocation of the genes that code for the TDF may wind up on the X chromosome instead. This is how it is possible to have an XX male who, due to the TDF being on his X chromosome, forms testes instead of ovaries but who nevertheless is usually sterile and unable to reproduce. 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. But becoming a male with all the right parts for reproduction involves much more.

The testes produce testosterone, a steroid hormone derived from cholesterol, by using different enzymes encoded on several different somatic chromosomes. 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, the Wolffian ducts degenerate and disappear and the Mullerian ducts develop into the female genital duct system. However, if the gonads become testes, the testosterone they produce attaches to androgen receptors (encoded on the X chromosome) and directs the Wolffian ducts to develop into the male genital duct system.

However, if the androgen receptor is absent or not working at all this causes a condition called Complete Androgen Insensitivity Syndrome (CAIS). In CAIS the testes produce testosterone but, without properly working androgen receptors to respond to it, the Wolffian ducts degenerate anyway leaving no genital duct system. This takes place in about one in 20,000 male births and these people are known as XY females. They will have testes that may migrate into the groin and labia, which if removed, will prove their true original nature. But they will often go undetected, appearing as normal females until they fail to menstruate at the appropriate age when all the other signs of puberty have taken place. It is then that they will be found to not have male or female internal organs, and a vagina that is usually smaller than normal and leads into a blind pouch going nowhere. How can this be? Read on!

On the way to developing into a normal male, in addition to testosterone, the testes also produce Anti-Mullerian Hormone (AMH) which is encoded on the 19th chromosome. AMH attaches to specific AMH receptors (encoded on the 12th chromosome) and instructs the Mullerian duct cells to degenerate and disappear. This is very important for male fertility because if both the Wolffian and Mullerian ducts develop, they physically interfere with each other. This usually results in sterility. It also explains why the XY female with CAIS looks like a normal female but has neither a male nor female genital duct system. Since her Wolffian ducts didn’t have working androgen receptors, they degenerated. But her testes also produced AMH which attached to the AMH receptors on her Mullerian ducts and made them degenerate too!

Here again we see that the 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. But there is still more to explain.

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. However, for this tissue to become normal male external genitalia requires much more stimulation of the androgen receptor than testosterone can provide. The cells in these tissues use an enzyme, called 5-alpha reductase (encoded on the second 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 embryonic tissues, it makes them develop into the penis, the scrotum, and the prostate gland. An XY person with a rare genetic disorder called 5-alpha reductase deficiency will have normally functioning testes and a normal male genital duct system, but their external genitalia will often be deformed and ambiguous making them incapable of participating in sexual intercourse and rendering them infertile. Again we see that the human embryo is destined to develop female parts by default or defective male parts unless acted upon by specific molecules, in this case the need for 5-alpha reductase to convert testosterone into DHT to adequately stimulate the androgen receptor.

To reiterate, the human embryo is destined to become female by default if not acted upon by several different chemicals. The TDF, usually on the Y chromosome, is what starts it down the male track by making the primordial gonads become testes; but much more is still needed. The testes use several enzymes encoded on different chromosomes to convert cholesterol into testosterone, which must attach to androgen receptors on the Wolffian ducts to form the male genital duct system. Without testosterone or properly working androgen receptors, the Wolffian ducts degenerate. In addition, to have normal male external genitalia requires a specific enzyme to convert testosterone into dihydrotestosterone so it can adequately stimulate the androgen receptors on the urogenital sinus, swellings, folds, and tubercle. If this enzyme is absent or not working right, the result is deformed and ambiguous external genitalia that cannot perform sexual intercourse, while if the androgen receptor is missing the result is female external genitalia. Finally, the testes also produce AMH which binds to AMH receptors on the Müllerian ducts to make them degenerate. If either of these are absent or not functioning properly, it results in the male having both a male and female genital duct system, which renders him infertile.

To paraphrase Stephen Meyer in The Information Enigma,different cell types require different proteins, different proteins require different genetically encoded instructions, and different instructions requires information that all human experience teaches comes from a mind and not material processes. Notwithstanding what it takes to produce properly working female parts, the information needed to make the male parts for reproduction requires the TDF, the enzymes to convert cholesterol into testosterone and testosterone into dihydrotestosterone, the androgen receptor, AMH and the AMH receptor.

The absence of any one of these results in either female parts or sterile male parts — and the survival of the human race hangs in the balance. Yet at birth and for many years afterward, human beings are incapable of participating in reproduction. What happens to change that? That’s what we’ll look at next time.

Photo credit: Gouwenaar [CC0], via Wikimedia Commons.