Hermaphrodite

In the animal kingdom, natural selection has promoted the development of two opposite sexes, the male and female genders. In most species, individuals belong to either sex, developing either a female phenotype with female external genitalia: a uterus, tubes, and two ovaries, or, depending on the presence of a testis-determining factor, a male phenotype with male external genitalia: epididymis and a testis. In a hermaphrodite, either in a true hermaphrodite or pseudohermaphrodite , elements of both genders are present in one individual. Some nematodes are physiologically true hermaphrodites (eg, Caenorhabditis elegans). Here, the molecular switch to determine whether a male or hermaphrodite is formed depends on an X-chromosome counting system (1), which involves primarily the xol-1 (2, 3) and tra-1 (4) genes. In mammals, however, male and female organs are not normally present in one individual.

 Due to the severity of the aberration, different types of hermaphrodites can be found. The clinical appearance of a hermaphrodite is characterized by intermediate sex forms of the external genitalia and germ line cells. Gonads that diagnose a true hermaphrodite are ovary and testis, or a combination of the two, the ovotestis. The combination of an ovary and ovotestis is most commonly found in hermaphrodites, followed by the combination of two ovotestes. When close to an ovary, the tubes and rudiments of an uterus are most commonly detected; when close to a testis, a vas deferens and an epididymis are present. In some cases, however, with a lower frequency of appearance, the opposite gender organs, or none, are developed: Tubes and uteri and/or vas deferens and epididymis are found, together with an ovotestis. This can occur because sex differentiation is highly dependent on hormones. As sexual organs are formed from primordial germ cells, as well as from soma cells, the gonadal sex does not fit to the genetical and/or cytological sex under certain circumstances.

 Besides true hermaphrodites, there are also pseudohermaphrodites, in which all other organs are female but a testis has developed. Due to the higher temperature in the body than in the scrotum, these cells are prone to the development of cancer and will be removed.

Regarding the karyotype of hermaphrodites, those with a Y-Chromosome are more likely to develop a testis than those without. The ovotestis contains both ovarian and testicular cells. The ovarian cells are in many cases normal, and primary follicles are also found. In contrast, the testicular cells show histological aberrations in true hermaphrodites, regardless of whether these cells are found in a testis or an ovotestis.

 Regarding the hormone production of hermaphrodites, they are characterized by normal levels of estrogens and gestagens. However, the levels are also dependent on the amount of normal ovHelvetica stroma present in the hermaphrodite. Spermatogenesis does not occur, but testosterone is produced, although it does not reach the levels of normal males. The reduced amounts are responsible for the virilization. There is only one case reported in which a hermaphrodite became a father. However, there are hermaphrodites that are fertile after removal of the testicular tissue and can give birth to children. This certainly does not depend solely on the presence of an ovary, but also on a physiological development of at least one of the tubes and of the uterus. Interestingly, all children born from female hermaphrodites were male. Roughly half the hermaphrodites were identified before the third year of life, but many hermaphrodites were identified only during or after puberty.

 During embryogenesis, germ cells become either spermatogonia or oogonia, depending on their genetic constitution. The genotype sex normally determines which type of gonads are developed. Further differentiation depends on the hormonal secretion of the gonads themselves, which consequently determines the phenotypic sex. The primordial gonad develops to an ovary, and the inner and external genitalia also tend to feminize, so long as the production of male hormones is not stimulated. In the case of secretion of male hormones, especially testosterone and mullerian inhibiting hormone, mullerian ducts do not develop; instead, wolfian ducts are formed that change the fate of the organs, and epididymis, vas deferens, and seminal vesicles evolve.

In cattle and goats, a special situation is found in a male and female twin. Due to the transfer of anastomosae, the development of mullerian ducts is inhibited in the female twin, which results in an infertile female. The external genitalia are female, but the uterus is rudimentary or missing. The male twin is fertile under normal circumstances. Apart from these special cases in twin births in cattle and goats, the biological reason for pathological hermaphroditism in mammals is still unclear.

Other genetically determined disorders related to gender are the Turner (X0) syndrome (5, 6) and surplus X-chromosomes, such as the XXY constitution (Klinefelter syndrome), which can now be detected using PCR techniques (7). Due to the absence of the Y-chromosome, the Turner syndrome is mostly linked with a female phenotype, although a mild masculinization has been reported (8). An additional X-chromosome leads to infertility and a reduced IQ. Additional Y-chromosomes, as found in XYY karyotypes, lead to extreme tallness, but not necessarily to crime, as was assumed in former times. In every case, the presence of a Y-chromosome leads automatically to a male phenotype, regardless of how many X-chromosomes were inherited. However, it must be kept in mind that it is not the Y-chromosome itself that triggers the development of male fate, but the SRY gene. Mutations within this gene can disrupt its function and consequently lead to female development, even though a Y-chromosome is present.

References

1. M. Nicoll, C. C. Akerib, and B. J. Meyer (1997) Nature 388, 200–204.

2. L. M. Miller, J. D. Plenefisch, L. P. Casson, and B. J. Meyer (1988) Cell 55, 167–183. 

3. N. R. Rhind, L. M. Miller, J. B. Kopczynski, and B. J. Meyer (1995) Cell 80, 71–82. 

4. C. P. Hunter and W. B. Wood (1990) Cell 63, 1193–1204. 

5. T. Ogata and N. Matsuo (1995) Hum. Genet. 95, 607–629. 

6. C. Geerkens, W. Just, K. R. Held, and W. Vogel (1996) Hum. Genet. 97, 39–44. 

7. A. Kleinheinz and W. Schulze (1994) Andrologia 26, 127–129. 

8. R. Medlej, J. M. Lobaccaro, P. Berta, C. Belon, B. Leheup, J. E. Toublanc, J. Weill, C. Chevalier, R. Dumas, and C. Sultan (1992) J. Clin. Endocrinol. Metab. 75, 1289–1292.