May 27, 2022 | Jerry Bergman

Genetic Finding Keeps Sexes Separate

X-Inactivation Study Finds More Differences in Males and Females,
explains why surgery cannot convert a male to a female or vice versa


by Jerry Bergman, PhD

Every high school student knows, or should know, that every cell in the male body is different than every cell in a female body. All of the normal cells in a male have XY chromosomes; in a normal female, XX chromosomes. The main exceptions involve enucleated cells, such as in the eye lens, and the blood cells. Two active X chromosomes results in an overdose of gene products, which is fatal for developing embryos and can lead to cancer in adult life.[1]  Because two X chromosomes in one cell overproduce proteins, one X chromosome has to be turned off. This process, called X-inactivation, deals with the problem of dosage compensation.  Consequently, early in embryonic development in females, one of the two X chromosomes is randomly and permanently inactivated in all of the cells that retain a nucleus other than egg cells.[2]

This X-inactivation phenomenon is called lyonization after Mary Lyon who discovered the process. Lyonization in females will result in one X chromosome in each cell like is true in males. A difference is, males have only one type of X chromosome, whereas females have two different X types, one type from the father and another type from the mother, but both will not be in the same cell. Because X-inactivation is random, in normal females the X chromosome inherited from the mother is active in some cells, and the X chromosome inherited from the father is active in other cells. For males, X-inactivation does not occur. Consequently, in males every cell that retains its chromosomes will have an X from the mother and a Y from the father.

Not all the chromosome genes are X-inactivated. Those located at the ends of each arm of the X and Y chromosome in areas called the pseudoautosomal regions are not inactivated. Furthermore, the same genes in the pseudoautosomal regions are present on both the X and Y sex chromosomes. As a result, men and women each have two functional copies of these genes which are essential for normal development. In addition to these differences, still other genetic differences between males and females exist.


One, called imprinting, is where certain genes are turned off in males and other genes are switched off in females. Whether particular genes are inactivated depends on which parent the genes were inherited from. If a person receives a particular gene from his or her other parent, the gene may be permanently turned off.[3] As a result, we have paternally imprinted genes and maternally imprinted genes.

Adding to this, a new control system has also been discovered.[4]

Little is known about how X-chromosome inactivation affects the development of reproductive cells. In mammals, oocytes develop from germ cells, precursor cells that migrate from early embryonic tissue to the developing gonads. Germ cells then undergo meiosis, an important chromosomal rearrangement process, which is responsible for the genetic uniqueness of each individual germ cell. Germ cells mature and eventually turn into functional sperm or oocytes.

The new research found certain genes are turned both on and off at the proper time, and a correct X-chromosome inactivation and reactivation sequence indicates normal germ cell differentiation. Thus, depending on many factors, the research

revealed a carefully orchestrated act of X-chromosome ‘yoyo’. If one X chromosome [is] briefly inactivated and then reactivated, it resulted in germ cells being four times more efficient for entering meiosis and transforming into egg cells compared to germ cells that have never turned their X chromosome ‘off and on’ again. In comparison, germ cells that failed to inactivate the X chromosome in the first place or reactivated it too rapidly showed abnormal gene expression and cell differentiation patterns.

Dr. Moritz Bauer, the co-first author of the study, explains one finding.

Our results also highlight how we need specific tools to study female cells. The vast majority of studies are performed using male cells, leading to a gender-gap in scientific knowledge. We therefore need to stop looking at female development through the lens of male cells, which will contribute to our understanding of sex-specific disease progressions.

What this means is that male cells and female cells are different even at the germ cell stage. These differences are now just being explored. This is one more observation which supports the fact that hormones and surgery cannot convert a male to a female, nor a female to a male. Sex operations and hormone therapy used in the so-called ‘transitioning’ from one sex to the other sex process is nothing more than cosmetic surgery. It is an attempt to change the appearance and does not make a male from a female, nor a female from a male. Furthermore,

The mammalian germline is characterized by extensive epigenetic reprogramming during its development into functional eggs and sperm. Specifically, the epigenome requires resetting before parental marks can be established and transmitted to the next generation. In the female germline, X-chromosome inactivation and reactivation are among the most prominent epigenetic reprogramming events, yet very little is known about their kinetics and biological function.[5]

The fact is “The kinetics and biological function of epigenetic reprogramming during mammalian germ cell development remain poorly understood.”[6] It appears, as this process is better understood, the conclusion that science cannot make a male from a female, nor a female from a male, will be even further supported.


As we learn more in genetic research, the conclusion that you cannot make a male from a female, nor a female from a male will likely be further supported. This corroborates the standard historical medical conclusion that gender dysphoria meant the need for a psychologist and not a surgeon.

An example of X-inactivation in mammals. From Wikimedia Commons


[1] Center for Genomic Regulation. 2022. Turning X chromosome ‘off and on again’ critical for oocyte development. ScienceDaily, May 23.

[2] National Library of Medicine. X chromosome. MedlinePlus.

[3] Phillips, T., and I. Lobo. 2008. Genetic Imprinting and X Inactivation. Nature Education 1(1):117.

[4] Center for Genomic Regulation. 2022. Turning X chromosome ‘off and on again’ critical for oocyte development. ScienceDaily, May 23.

[5] Severino, J., et al. 2022. Controlled X‐chromosome dynamics defines meiotic potential of female mouse in vitro germ cells. The EMBO Journal, May 23; DOI: 10.15252/embj.2021109457

[6] Severino, et al. 2022.

Dr. Jerry Bergman has taught biology, genetics, chemistry, biochemistry, anthropology, geology, and microbiology for over 40 years at several colleges and universities including Bowling Green State University, Medical College of Ohio where he was a research associate in experimental pathology, and The University of Toledo. He is a graduate of the Medical College of Ohio, Wayne State University in Detroit, the University of Toledo, and Bowling Green State University. He has over 1,300 publications in 12 languages and 40 books and monographs. His books and textbooks that include chapters that he authored are in over 1,500 college libraries in 27 countries. So far over 80,000 copies of the 40 books and monographs that he has authored or co-authored are in print. For more articles by Dr Bergman, see his Author Profile.

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