The recent finding that the XY fertile females of Akodon have the same SRY gene sequence as that of XY males underscores our continuous need to understand the complexity of sex differentiation and determination.These models also have significance for understanding variations in human sex determination and differentiation as well as for intersex conditions.
XY females exist in humans. They also exist in mice, horses and many other mammals. Typically in mice, horses and humans, XY females are infertile. There are some exceptions. However, despite whether an XY female is fertile it cannot be denied that they are female.
That the anatomical configuration does not match what is merely EXPECTED from chromosomes doesn't negate the fact that the anatomical configuration is a far better marker for sex identification than a Y chromosome or even Y chromosomal DNA.

In mice, horses and humans, what is referred to as "male specific DNA" can be inactivated (essentially turned off).
Furthermore, genes on the X chromosome may turn an individual with "normal Y chromosomal DNA" into a female and genes which are not on an X or a Y chromosome may do the same.
In fact, environmental disruption of an individual who carries "male spoecific DNA" may result in the individual developing as a female.

Having male specific DNA or an XY chromosome pattern does not equal a male person anymore than having genes for brown eyes necessitates that a person does have brown eyes. Eye color and sex are phenotypes-observable physical traits.

Female traits can dominate in individuals with an XY pattern due to a host of other biochemical and environmental factors. Although (see above) several mechanisms are known that cause mice, horses, and other mammals to become female in the presence of an XY genotype, many other mechanisms are unknown. Such is likely to be at work in Akodon.

It is unknown why so many XY Akodon are female-moreso in the presence of an SRY (typically male) gene that is no different than that found in XY males.
Furthermore it is unknown why Akodon XY females are typically more fertile than XY females of other mammalian species. It is also unknown why Akodon XY fertile females are even more fertile than their XX female counterparts.

In non-Akodon mice, XO females are quite fertile. In XO individuals with Turner's syndrome, XO females are typically infertile. But this is not always the case as some XO humans with Turner's Syndrome are fertile.
Likewise XY female mice are often infertile as are XY human females. But again, this is not always the case as there are fertile XY female mice and fertile XY female humans.

What causes increased fertility in XO female mice over XO female humans and XY female Akodon over XY female mice and XY female humans?

For female mice is seems that there is Y chromosomal DNA which hampers female fertility but the so called SRY gene is not a significant one. Y chromosomal DNA may provide even less of an impairment for fertility in XY female humans than it does for mice.

As mentioned, XO female mice which lack an entire Y chromosome are rather fertile whereas XO female humans with Turner's Syndrome are rather infertile. Since in each of these cases (for mice and humans) there is no Y DNA, we see a vast difference in the fertility in female mice vs. female humans without any influence at all of a Y chromosome or Y chromosomal DNA.

Therefore it seems that the X chromosome plays an important role in this difference between XO female mice and XO female humans. Humans and mice both need an X chromosome for survival. But genes from one X chromosome seems to assist in fertility more in XO female mice than it does in XO female humans. However, since there ARE fertile XO female humans with Turner syndrome, a second X chromosome is not necessary.

It is not necessary for mice and it is not necessary for humans. During the making of oocytes (future eggs) in a process known as meiosis, chromosomes pair as partners and synapse together. (Remember, one has been derived from the egg and its partner from a sperm). Thus, during meiosis, chromosome 1 pairs and undergoes synapsis with its partner chromososme 1, chromosome 2 with 2, 3 with 3, X with X and so on.

In the lack of a second X chromosome in XO female mice and in XO female humans, the pairing and synapsis process is disrupted. What happens is that the genes on the unpaired/unsynapsed X chromosome are turned off.

This prohibits fertility. It does so in mice and it does so in humans.

In fact, in XO fertile mice, there is evidence that the fertile XO female mice are fertile because the single X chromosome loops around and synapses with itself (a process called self-synapsis).
As a result, genes from the single X are not silenced and ferility is maintained. The self-synapsis rate for XO female mice is about 27%.

The self-synapsis rate of the X chromosome for XY Akodon females is about 60%. We don't know what the rate is for XO fertile human females or for XY fertile human females.

With technologies that could increase self-synapsis, it would likely be possible to increase the fertility rates of both XO females and XY females.

The Akodon and other rodents are not only informing us about why so-called sex chromosomes don't prevent mammals in general from being a male or a female despite having a Y chromosome or not, they are also giving us information that demonstrates that not having a second X chromosome does not prevent mammals from being a fertile female.

This has important relevance for individuals such as intersexed individuals who are incorrectly told by some that their sex (or their fertility) needs to be defined by their having a Y chromosome or a second X chromosome.

M Italiano, MBBS (AM)