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Sex Reversal: Definition, Types, and Examples

Sex Reversal: When Males Grew Ovaries Instead of Testes

Sex reversal has been reported in the case of invertebrates and it is not an unusual phenomenon in them. Some fishes and reptiles in the case of vertebrates under some conditions like social and environmental factors can undergo sex reversal. It is intriguing to research whether this phenomenon can occur in the case of mammals that by adulthood have fully differentiated gonads. If so, then what factors initiate those changes or alterations and to what extent.

Sex Reversal Occurring in Nature

Sex reversal refers to the process wherein the sex identity in terms of gonads and other secondary sex traits are changed to the other gender. This phenomenon can be observed easily in invertebrates like nematodes. These free-living invertebrates change their gender within their population due to unfavorable conditions. The sessile molluscan, slipper-shell male snails can alter their sex during their young phase when a male comes in proximity. Vertebrates like goby fish can also undergo sex reversal when the alpha male of their population dies, then the largest female becomes male.

Genetic Factors in Mammalian Sex Reversal

In the case of mammals, sex reversal is plausible only during early gonadal development as the sex is determined genetically by the sex chromosomes. In mammals, the gonads show very minimal plasticity as environmental factors do not affect their expression but rather it is determined chromosomally. This phenomenon can be seen in humans with genetic tendencies. Male are characterized by having heterozygous sex chromosomes, XY, while the female has homozygous sex chromosomes, XX.

The X chromosome is not the sex determiner but rather the sex-determining region is located in the sry gene of the Y chromosome. This gene initiates the development of testes in males. Any mutation or alteration in this gene that makes it dysfunctional can deter the development of testis, so the protein product of this gene was termed as a testis-determining factor (TDF).

In an experiment performed on the mouse embryo in1991, researchers could reverse the sex on the introduction of SRY gene and as a result, the chromosomally female mice started showing the development of testis. Even though, Y- chromosome has fewer genes and is smaller than the X chromosome it can determine the sex of an organism due to the SRY gene it possesses.

Role of Junk DNA Enh13 in Sex Reversal

Francis Crick Institute scientists found another region of a chromosome in mice that could be involved in gonadal sex reversal. This particular region was a non-coding junk DNA. Only around 2% of genes are vital and are expressed in the case of humans, the rest do not code for proteins and are termed junk DNA. Enhancer 13 may be junk DNA but has significant functions in mice. If this is missing it can lead to sex reversal in males, leading to the expression of female genitalia and production of female ovaries.

This finding exemplified the role of Enh13 in the early development of gonad by stimulating SOX9 protein production. They are expressed when TDF proteins bind upstream to the enhancer sequence of the SOX9gene. Increased production of SOX9 proteins determines the male fate of the embryo.

Impact of Enh13 Findings on Sex Reversal

These findings on Enh 13 could have an impact on the understanding of the sex reversal process in mammals according to Dr. Nitzan Gonen. Their research team has recognized 4 enhancer regions, even a single enhancer can have prominent regulation over the determination of sex. Utilizing such studies an in-depth understanding of the mechanisms involved in sex reversals can be studied in mammals.

Sex reversal in mammals is limited and gonadal plasticity is observed only in the embryonic phase. An adult has fully differentiated gonads that cannot be altered. In cases of intersexuality where both gonads form, only one type will be functional.

Some cases of sex reversal in humans have been reported. For example, one such case has been seen in the UK, where 2 brothers and their paternal uncle are male anatomically but are genetically female having the karyotype, XX. This can be attributed to genetic mutations. More research needs to be done to pinpoint the molecular mechanisms behind sex reversal in humans.

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