EMBRYONIC SEX DETERMINATION
Almost everyone who has received biology education at the high school level will say that the sex of the human embryo is determined from the very first day with fertilization. Because, as in other mammals, the determination of sex in humans is mediated by genes from the male and female. The human cell contains a total of 46 chromosomes in 23 pairs. One of these pairs is the sex chromosome, called the gonosome. The human gonosome has an XX structure in females and an XY structure in males. During the formation of reproductive cells, as a result of meiotic division, the chromosome pairs separate from each other, reducing their number by half. Therefore, while in females, egg cells carrying X chromosomes, each with 23 chromosomes, are formed, the sperm cells of males, with 23 chromosomes, can have an X or a Y chromosome. Since the egg coming from the mother during fertilization will always have an X chromosome, if the sperm from the father has an X chromosome, the embryo will be a female with XX chromosomes; if the sperm has a Y chromosome, the embryo will be a male with XY chromosomes.
|
|
Source: Kateryna Kon/Science Photo Library/Getty Images. |
Although the sex formation process outlined above proceeds in this way, it should be known that such a description is quite incomplete. In fact, in some cases, this information can even be misleading. Because the transformation of genetic information, called the genotype, into physical, biochemical, and behavioral characteristics, called the phenotype, in an organism occurs as a result of a gradual and complex process known as gene expression. In this process, the genetic information in DNA is first read, then copied and transported to ribosomes, where protein synthesis occurs. The produced proteins function as enzymes, hormones, building blocks, or carrier molecules in the body, enabling the formation of the phenotype.(17)
The determination of sex is also the result of such a complex mechanism. If these mechanisms do not function healthily as expected, individuals with an XY genotype can develop with a female phenotype, and it is also possible for individuals with an XX genotype to develop with a phenotype close to male.
THE REPRODUCTIVE SYSTEM OF THE EMBRYO IN THE FIRST SIX WEEKS
Another important component of the embryo's reproductive system is the sexless (bipotential) reproductive stem cells called PGC (Primordial Germ Cells). These initial cells, which will later turn into egg and sperm cells, migrate from the yolk sac starting from the 5th week, enter the embryo, and settle in the genital ridge. After the 6th week, with the differentiation of the gonads, PGCs will undergo processes called spermatogonia in males and oogonia in females, forming the immature precursors of sperm and egg cells.
|
| Initial genital formation in the embryo |
Another sexual formation developing in the embryo is the Wolffian and Müllerian ducts, which form near the genital ridge starting from the 4th week. The Wolffian ducts play a fundamental role in the development of the male reproductive system in the embryonic process and over time form the male reproductive organs called the sperm ducts, epididymis, and vas deferens. The Müllerian ducts, during embryonic development, form the basic structures of the female reproductive organs: the uterus, fallopian tubes, and the upper part of the vagina. (18) Regardless of the embryo's sex, both Wolffian and Müllerian ducts begin to form in all embryos from the 4th week. However, after the 6th week, according to sex, in males, the Wolffian ducts continue to develop while the Müllerian ducts regress and disappear. In females, the opposite occurs; the Müllerian ducts develop and the Wolffian ducts disappear.
As a result, none of the components that form sex in the human embryo show differences as male or female during the first 6 weeks of pregnancy.
|
|
Development of gonads and genital ducts in the embryo |
SRY GENE
The first and most fundamental factor determining sex development in the human embryo is a gene fragment called the SRY (Sex determining Region on chromosome Y) gene. As the name suggests, this gene is located on the Y chromosome, which is only found in male individuals. In female individuals, the SRY gene is absent. The first step of the differentiation process of the male embryo from females is the activation of the SRY gene at the end of the 6th week of pregnancy. Until that time, while the sexual formations in male and female embryos proceed identically, with the activation of the SRY gene and the start of SRY protein production, the male embryo heads in a different direction, while the female embryo continues its path as before.(19)
With the activation of the SRY gene at the end of the 6th week in the male embryo, SRY protein secretion begins. The function of this protein, also called TDF (Testis Determining Factor), is to ensure the transformation of the gonads into testes and to prevent the development of ovaries. With the appearance of the SRY protein, the formation of Sertoli cells in the gonads is triggered. Sertoli cells cause the production of Leydig cells, which are responsible for secreting testosterone, and also ensure the secretion of MIF (Müllerian Inhibiting Factor). MIF, also called AMH (Anti-Müllerian Hormone), is the hormone that causes the regression of the Müllerian ducts in the male embryo. Testosterone, which begins to be produced by the Leydig cells in the developing testes over time, combined with other signals, leads to the differentiation of the Wolffian ducts into the epididymis, vas deferens, and sperm ducts.(20) (21)
In the female embryo, in the process after the 6th week of pregnancy, the previously sexless gonads mature normally and transform into ovaries. Due to the absence of the SRY protein, while the Wolffian ducts, the basic structure of the male reproductive organs, disappear, the Müllerian ducts continue to develop, forming the uterus, fallopian tubes, and the upper part of the vagina. After the transformation of the internal sexual organs, the PGC cells also begin to change to form the egg cells.
Studies have surprisingly shown that both male and female sexual development and the brain's sexual metamorphosis are processes dependent on the presence or absence of male hormones, and that ovarian hormones have no significant effect on this process, even in females.(21)
As a result, with some exceptions, if the embryo has the SRY gene and it is activated when the time comes, the embryo will undergo transformation and acquire the male sex. If this gene is not present, since male hormones will not be secreted, the embryo will continue its path as female. As can be understood from this, there are no distinguishing features that separate the male embryo phenotype from female embryos in the process until the SRY gene is activated.
SWYER SYNDROME
|
| Maya Posch (Germany), an individual with Swyer syndrome |
XX MALE SYNDROME (DE LA CHAPELLE SYNDROME)
42nd DAY
As can be understood from the topics discussed so far, although the
embryo's genotype is determined with fertilization, the first and most
important factor in the shaping of the phenotype according to sex is whether
the SRY chromosome is active or not. Research has revealed that the SRY
protein (TDF) produced by the SRY gene is first observed in the sexless gonads
approximately on the 42nd day after fertilization. In the book "Hormones"
written by Prof. Gerald Litwack, the observation of the SRY protein in the
embryo and the resulting beginning of testis formation are expressed in
English as follows:
“The SRY gene product, SRY, is detected in the bipotential gonad of XY
individuals at about 42 days. The protein contains an high-mobility group box
of 79 amino acids that binds to specific regions of DNA, causing the DNA
molecule to bend. This bending is thought to make these regions more
accessible to other transcription-regulating proteins that ultimately bring
about the differentiation of the gonadal cells, some to Sertoli cells, some to
Leydig cells. By the end of the sixth week after conception, the Sertoli cells
of the fetal testis have begun to differentiate and secrete AMH (One of the
First Sex-Specific Hormones)”
“The SRY (protein), the product of the SRY gene, is seen in the bisexual
(sexless) gonads of XY (male) individuals at approximately 42 days. This
protein contains a high mobility box consisting of 79 amino acids that binds
to specific DNA regions and causes the DNA molecule to bend. This bending is
thought to make the specified regions more accessible to other transcription
regulatory proteins. As a result, gonadal cells differentiate, some turning
into Sertoli cells, and some into Leydig cells. By the end of the sixth week
after fertilization, the Sertoli cells in the fetal testes have begun to
differentiate and secrete AMH (One of the First Sex-Specific Hormones).”(23)
The scientific data explained so far regarding the shaping of the embryo's sex
as male or female perfectly coincide with two authentic hadiths narrated from
Hz. Muhammad (s.a.v.). These hadiths, found in Sahih-i Muslim, which is
mentioned as one of the two most reliable books after the Quran in Islamic
literature, were recorded in the 9th century AD, and very old manuscripts of
this book have survived to the present day. These hadiths are as follows:
“When forty-two nights have passed over the drop (nutfa), Allah sends an angel
to it, who shapes it and makes its ears, eyes, skin, flesh and bones. Then the
angel says, ‘O Lord, is it male or female?’ And your Lord decides what He
wishes, and the angel records it. Then the angel says, ‘O Lord, what is its
term?’ And your Lord decides what He wishes, and the angel records it. Then
the angel says, ‘O Lord, what is its provision?’ And your Lord decides what He
wishes, and the angel records it. Then the angel departs with the page (of
destiny) in his hand, and he does not add anything to what he was commanded
nor subtracts from it.” Muslim:(2645).
“Hudhaifa b. Usaid reported directly from Allah's Messenger (ﷺ) that he said:
When the drop of (semen) remains in the womb for forty or forty five nights, the angel comes and says: My Lord, will he be good or evil? And both these things would be written. Then the angel says: My Lord, would he be male or female? And both these things are written. And his deeds and actions, his death, his livelihood; these are also recorded. Then his document of destiny is rolled and there is no addition to nor subtraction from it.” Muslim:(2644).
As can be seen, the determination of the embryo's phenotype as male or female
is expressed as the 42nd day both in hadith number 2645 and in the book
"Hormones" written by Prof. Gerald Litwack. That this period corresponds to an
approximate time and can vary is stated both in hadith number 2644 and in the
same book. In many scientific articles, the activation time of the SRY gene
and the time when sex becomes apparent are indicated as the end of the 6th
week, between 41-44 days, etc.
Another point that draws attention in hadith number 2645 is that it is said
that the angel sent on the 42nd day gives form (suret) to the embryo and
determines the shape of the embryo's ear, eye, skin, flesh, and bone. The
expressions "giving form" and "shaping" in this hadith mean "shaping what
exists," not "creating from nothing." Just as the gonads and
Wolffian-Müllerian ducts, which have the potential to turn into the sexual
organs of both men and women (bipotential), are created in the still sexless
embryo before the 6th week, and then these change and separate into male and
female with the activation of the SRY gene, although the eye and ear pits of
the embryo form before the 42nd day, their rapid development and acquisition
of distinctive characteristic features will occur from the beginning of the
7th week.
- The embryo's average length is 9-12 mm (about the size of a coffee bean)
- The embryo grows very rapidly from this week until the 20th week.
- Facial features begin to appear in the embryo in outline this week; eyes, transparent eyelids, ears, palate, teeth, and nose form.
- Arms and legs begin to lengthen, and finger outlines form.
- The respiratory system appears as 2 lung buds.
- The tail, an extension of the spine, begins to shrink, and the coccyx becomes prominent.
- Liver cells begin blood production for the first time this week. (This task was previously performed by the yolk sac)
- The kidneys appear this week.
- The pituitary gland forms this week.
- Since the placenta is not yet fully formed this week, the embryo is still nourished by the yolk sac.(24)
GENOTYPE OR PHENOTYPE?
A question may arise here; even if the embryo's phenotype begins to take
shape on the 42nd day, considering that the genotype is determined on the
first day with fertilization, how should the angel's coming on the 42nd
day be understood?
As an answer to this question, first, we should say this; we can think of
the reflection of what is in the genotype into the phenotype like the
construction of an architectural project on site. The genes the embryo
receives from its mother and father carry the information of its entire
physiognomy. The embodiment of this information in real life requires will
and power. According to Islamic belief, angels are the representatives of
this power. They supervise and witness the creation of the true power
holder, Allah. The supervision of angels is not like helping or mediating
and does not stem from a need. They are only entrusted with certain duties
in a manner worthy of the magnificence of Allah's creation and act as
stewards for actions that might be perceived as insignificant or evil in
the view of humanity. We can liken angels, so to speak, to the protocol
officers a sultan takes with him when going out among his subjects. Those
in these entourages are not actually the executors, but their presence is
necessary for the people to comprehend the grandeur of the sultan's
position.
Another issue that needs to be known about angels is that their knowledge
is limited. No angel's knowledge can be compared to Allah's knowledge.
They can only know as much as Allah informs them. In fact, in some cases,
human knowledge can be superior to angelic knowledge. When Hz. Adam was
created and the duty of caliphate was given to Adam, not to the angels,
the angels could not understand the wisdom in this. When Allah taught Adam
the names that are the source of all sciences and asked both the angels
and Adam to tell these names, Adam did what the angels could not do, and
the angels confessed their incapability by saying, "Glory be to You! We
have no knowledge except what You have taught us. Indeed, it is You who is
the Knowing, the Wise." (Baqara, 2/32).
From this perspective, it can be said that the knowledge and duty of the
angel coming to the embryo on the 42nd day are limited to what is given to
it. So to speak, the coming angel is (in the sense of stewardship) not the
architect of this project but only the site chief. As understood from the
hadith, with the coming of this angel supervising Allah's creation and
execution, the information recorded in the genotype was put into life
through the angel's hand and transferred to the phenotype, the embryo's
sex became apparent, its development gained great speed, and its
characteristic features began to emerge. These are also in complete
agreement with scientific data. It is expected that the truths conveyed to
us by Hz. Prophet (s.a.v), who was sent as a mercy to the worlds, would be
like this. Because regarding him, Almighty Allah says in the first 4
verses of Surah An-Najm:
1-By the star when it descends,
2-Your companion [Muhammad] has not strayed, nor has he erred, nor has he been deceived.
3-Nor does he speak from [his own] inclination.
4-It is not but a revelation revealed [to him].
1 Pheromones are special molecules secreted to provide chemical communication between living beings and to affect the behavior and physiology of individuals of the same species.
2 The word "Bipotential" means "having both potentials to develop as male or female," but for convenience, it has been translated as "sexless".
BIBLIOGRAPHY:
[16] "Mechanisms of Sex Determination." Open Textbook Library, University of Minnesota, open.lib.umn.edu/evosex/chapter/8-5-mechanisms-of-sex-determination/.
[17] "Gene Expression." Nature Scitable, www.nature.com/scitable/topicpage/gene-expression-14121669/.
[18] Acar, Murat, et al. "Andrology." Journal of Andrology, vol. 15, no. 52, 2015, pp. 57–61, jag.journalagent.com/androloji/pdfs/and_15_52_57_61.pdf.
[19] "Sex Determination." Visualizing Embryology, www.visembryo.com/story4072.html.
[20] "The Molecular Basis of Human Sex Determination." NCBI Bookshelf, National Library of Medicine, www.ncbi.nlm.nih.gov/books/NBK557601/.
[21] Yılmaz, M. O., and B. Aydın. "Sex Development in Mammals and Its Hormonal Control." Journal of the Veterinary Medical Association, vol. 80, no. 3, 2009, pp. 23–28.
[22] "Swyer Syndrome." Cleveland Clinic, my.clevelandclinic.org/health/diseases/swyer-syndrome.
[23] Litwack, Gerald, PhD. Hormones: Fourth Edition, Academic Press, 2022.
[24] "Weekly Development of the Baby During Pregnancy." Esra Esim Büyükbayrak, www.esraesimbuyukbayrak.com/gebelik-surecinde-hafta-hafta-bebegin-gelisimi/.
Comments
Post a Comment