In most mammals, us included, biological sex is determined
by a lottery between two letters: X and Y, the sex chromosomes. Inherit one X
each from mom and dad, and develop ovaries, a womb and a vagina. Inherit an X
from mom and a Y from dad, and develop testes and a penis.
But there are rare, mysterious exceptions. A small number of
rodents have no Y chromosomes, yet are born as either females or males, not
hermaphrodites. Now, scientists may be one step closer to figuring out how sex
determination works in one of these rodents.
In a study published in Science Advances on Friday, Japanese
scientists suggested that cells of the endangered Amami spiny rat, from Japan,
are sexually flexible and capable of adapting to either ovaries or testes. When
the researchers injected stem cells derived from a female rat into male embryos
of laboratory mice, the cells developed into and survived as sperm precursors
in adult males. The result was surprising since scientists have never been able
to generate mature sperm from female stem cells, largely because sperm
production normally requires the Y chromosome.
Found only in the subtropical forests of an island in Japan
called Amami Oshima, Amami spiny rats are threatened by habitat destruction,
competition with black rats not native to the island and predation by mongooses
and feral cats and dogs. Their range has been reduced to less than 300 square
miles, an area smaller than New York City.
Both female and male Amami spiny rats have only one X
chromosome, an arrangement only known to occur in a handful of rodents among
mammals. Arata Honda, associate professor at the University of Miyazaki and the
lead author of the paper, said in an email that he was partly motivated to
study Amami spiny rats in the hope that learning about them might reduce their risk
of extinction.
No one knows how or why, but at some point the rats lost
their Y chromosome and, along with it, an important gene called SRY that’s
considered the “master switch” of male anatomical development in most mammals.
It’s possible that a new gene that wasn’t linked to the Y
chromosome took over the role of SRY in these rats, said Monika Ward, a
professor and expert on the Y chromosome at the University of Hawaii in
Honolulu who was not involved in this study. In addition, research has shown
that other genes involved in male sexual differentiation were not lost, but
rather transferred from the Y chromosome to other parts of the rat’s genome,
including to the X chromosome.
Because the rats are endangered, scientists cannot directly
do experiments on them. To get around this, Dr. Honda and his colleagues
converted skin cells from the tail tip of a female Amami spiny rat into special
stem cells called induced pluripotent stem cells (also called iPS cells), which
can multiply indefinitely and become any other cell type in the body. The
scientists injected the stem cells into mice embryos and transplanted the
embryos into female mice, which birthed 13 so-called chimeras.
After the chimeras reached adulthood, the researchers
located the spiny rat iPS cells within their bodies. They were surprised to
find some iPS cells appeared in the ovary as immature egg cells, and others in
the testis as immature sperm cells.
This study shows that the spiny rat’s sex cells have
“astounding” fluidity, said Diana Laird, an associate professor in reproductive
sciences at the University of California, San Francisco, who was not involved
in the study. The cells were able to sense whether they were in an ovary or
testis, and “not only hear but obey the signals” coming from that foreign
environment, she added.
Dr. Ward emphasized that these results are not universal —
if you were to take iPS cells from a normal female mouse and put them in a male
embryo, the few cells that became sperm precursors would die very quickly. The
female stem cells in this study were able to approach mature sperm development
because of the Amami spiny rat’s unique biology, she said.
The study is also significant because the researchers
managed to create chimeras from an endangered species, said Marisa Korody, a
postdoctoral associate at the San Diego Zoo Institute for Conservation Research
who researches how iPS cells might be used to protect endangered animals.
“One of the lofty goals we have for using stem cells,” she
said, is “to differentiate them into egg and sperm and hopefully create embryos
that can be transplanted into a surrogate.”
But there are limits to the findings because the researchers
have not yet shown that the spiny rat’s stem cells can fully develop into
mature eggs and sperm. “That’s the million dollar question,” Dr. Laird said.
This post first appeared on NY
TImes.
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