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In human sexual development, there are two sexes: males who have one X and one Y chromosome, and females who have two X chromosomes (Gilbert, 2003). Humans are classified as mammals and there sex is determined by the Y chromosome, in particular, the presence of a certain gene, the SRY gene, on the Y chromosome (Kanai, 2005). This gene determines whether or not the bipotential gonad becomes a testis (male) or an ovary (female) by acting as a repressor of a negative regulator of male development – basically, SRY clears the way for the testis to form (Gilbert, 2003 and Kanai, 2005). After SRY is activated, it appears to us that SOX9, a gene also critical for the males in this category of beings, gets turned on creating a surge of events that induce differentiation of the male testis (Kanai, 2005). Other genes that appear to play a role in sex determination are WT1, SF1, and LHX9 (Gilbert, 2003 and Vilain et al., 1998).

SRY expression directly results in the differentiation of Sertoli cells from supporting cells (mesonephric cells) in the genital ridge (Koopman, 2001 and Gilbert, 2003). These cells are important for further development of the testes by inducing the migration of cells from adjacent mesonephroi (mesonephric cells), which are necessary for the development of the cords and growth of the cell population in the testis (Koopman, 2001 and Gilbert, 2003). The Sertoli cells send out signals that inhibit the signal that induces oogenesis, and they send signals that induce differentiation of Leydig cells which secrete testosterone (Koopman, 2001). One of the most important and foremost product of the Sertoli cells is the anti-Müllerian hormone (AMH), which is involved in the regression of the Müllerian duct – it forms internal female structures (e.g. Fallopian tubes, uterus, and cervix) if AMH is not present to induce apoptosis of the duct cells(Josso et al., 2005 and Gilbert, 2003). Testosterone is important for the induction of the development of the Wolffian duct (precursor to the epididymis, vas derferens, and seminal vesicles) and male secondary sexual characteristics (Koopman, 2001 and Gilbert 2003). Induction of the male genitalia (which includes the scrotum, penis, urethra, and prostate) from bipotential external structures occur when testosterone is converted to dihydrotestosterone (DHT), which is responsible for this induction (Gilbert, 2003).

With female sex development, the initial steps appear to be the same as in males. The genital ridge becomes the bipotential gonad with the expression of SF1, WT1, and LHX9; once there is a bipotential gonad, differentiation begins (Gilbert, 2003). Ovaries in females develop with the expression of DAX1 and WNT4: DAX1 expression opposes the function of SRY and down regulates expression of SF1, which clears the path for WNT4 expression (Gilbert, 2003). DAX1 and WNT4 are both on the X chromosome, but it depends on whether or not there is a Y chromosome that WNT4 is expressed (Gilbert, 2003). DAX1 and SRY compete for the repression and expression, respectively, of the SF1 gene; if the Y chromosome is present, then SRY out-competes DAX1 and there is testis development and a male offspring (Gilbert, 2003). If there is no Y chromosome, then DAX1 wins and SF1 is repressed giving way to WNT4 and ovary development, and thus a female offspring (Gilbert, 2003).

Without AMH secreted by Sertoli cells, the Müllerian duct stays intact and forms the Fallopian tubes, uterus, and cervix (Gilbert, 2003). The initial sex cords degenerate in the ovary and the cortical sex cords arise in their place (Gilbert, 2003). These cords form clusters, with each cluster surrounding a germ cell; the germ cell will become the ova, with the sex cords differentiating into granulosa cells (Gilbert 2003). Thecal cells that form estrogen-secreting differentiate from mesenchyme cells, and the estrogen secreted plays a vital role in the development of the Müllerian duct into female internal genitalia (Gilbert, 2003).

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Our method of sexual differs somewhat from the humans, particularly with the greater number of sexes we have; however, much of the mechanisms are the same. We use the same chromosomes to determine sex as theses humans, and the Y chromosome even determines maleness, but all the males in our system have three sex chromosomes: XXY. Some humans have this as well (they call it Klienfelter Syndrome), where there are the same three sex chromosomes, but we do not have defects in neural function and development like these humans, we function just fine mentally, really. The reason is because we have evolved so that an X chromosome can completely silence any one (and only one) extra X chromosome when there are more than two chromosomes, effectively only having two functioning sex chromosomes, the X and Y in males. In females, we still have one active X chromosome and another incompletely silenced one. While the males have three chromosomes, the females only have two and sexual development is very similar to human females. XXY males and XX females can give rise to offspring with three different sets of sex chromosomes: XX (female), XXY (male), and XYXX (hermi). During meiosis of the primary spermatocyte, one of the X chromosomes is inseparable from the Y chromosome, so our sperm is able to hold up to two sex chromosomes, thus allowing trisomy in the male sex chromosomes. So when the sperm enters the egg, it can contribute one or two sex chromosomes, whereas is humans, only one is contributed by the sperm. The same case exists with the female egg: either one or two X chromosomes can be contributed to the offspring. When the sperm contains an X chromosome, a female offspring (XX) develops, and when an X and Y chromosome are in the fertilizing sperm, it gives rise to a male offspring (XXY). The sperm with two sex chromosomes are bigger than the ones with just one. An XXX offspring can never happen because there are effectively two active X chromosomes, and that would be lethal.

	Egg w/ X	Egg w/ XX
Sperm w/ X	XX	lethal
Sperm w/ XY	XXY	XXXY

The third sex, with XYXX sex chromosomes, takes place when the egg is XX and the sperm is XY. We develop similarly to humans with dicephalus, where there are two heads (but still only one brain) and necks and one body; however, unlike your two headed-single bodied people, we are quite viable because we have evolved to resist any cardiac problems that would develop (Bondeson, 2001). For those of us who develop into Hermis, which is as common as male and female, separation of the fertilized egg not only occurs at the dorsal region, but also at the ventral region. Ventral separation is only slight and only enough to confer two distinct regions where there can be development of the two major sex characteristics: male and female genetalia, both external and internal. So there is expression of both XY and XX sex phenotypes, but only in the genital region.

How is it even possible to get two sexes in one, or even four chromosomes? Well, it all starts out when a male and a female mate. The sperm enters the egg and a fertilized egg develops. With males and females, there is no separation of the fertilized egg ventrally, unlike with Hermis, due to the genes involved. This slight separation is the result sex linked recessive genes that cause specific areas of the presumptive genital region to extend and separate (need three X chromosomes to be positive for the genes and regulatory genes on the Y chromosome to confer dominance), allowing two regions for two types of genetalia. We reproduce the same way humans do: insert the male member into the female and ejaculate to give the sperm access to the eggs. Hermis reproduce only through self fertilization because there are no sexual positions that would allow otherwise – at least I can’t think of any. The offspring of the Hermis are always male because Hermis sperm are always double sex chromosome carriers.

You may ask: doesn’t interbreeding result in less viable offspring? Well, it would is it weren’t due to our environment. You see, we live on a planet with a poor ozone layer which is not too far from a star. The radiation mutates some of our DNA, especially those not protected by radiation absorbing proteins (the hDNA, human DNA, do not have these genes), allowing for genetic variation. Now, we are not sure how this extra sex arose, but from archeological studies, we know that our ancestors only had two sexes, like the humans. There have been some theories, and the most favored involves reproduction: it makes it easier because it is right there! You don’t have to go through the whole dating thing, meeting the parents, etc. So much less unneeded stress!

Koopman P (2001). Gonad development: signal for sex. Current Biology, 11, pp. R481-R483.

Vilain E and McCabe ERB (1998). Mammalian sex determination: from gonads to brain. Molecular Genetics and Metabolism, 65, pp. 74-84.

Kanai Y, Hiramatsu R, Matoba S, Kidokoro T (2005). From SRY to SOX: mammalian testis differentiation. Journal of Biochemistry, 38, pp. 13-19.

Josso N, Belville C,di Clemente N, and Picard, JY (2005). AMH and AMH receptor defects in persistent Müllerian duct syndrome. Human Reproduction Update, 11 (4), pp. 351-356.

Gilbert, Scott F. Development Biology. 7^th Editon. Massachusetts: Sinauer Associates, Inc., 2003.

Bondeson J (2001). Dicephalus conjoined twins: a historical review with emphasis on viability. Journal of Pediatric Surgery, 46 (9), 1435-1444.