OF MICE AND WOMEN
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
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.
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.
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.
causes increased fertility in XO female mice over XO female
humans and XY female Akodon over XY female mice and XY
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
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
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.
prohibits fertility. It does so in mice and it does so in
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
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.
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
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)