Article: Retinoic acid may control germ cells

By Charles Choi
Retinoic acid may control germ cells
Studies in Science and PNAS may overturn dogma of genetically programmed
fates for gonadal cells
[Published 31st March 2006 06:33 PM GMT]

Retinoic acid appears to control the timing and perhaps the choice for germ
cells in the developing mouse to begin changing into eggs or sperm,
scientists report in the March 30 online edition of Science. Their paper,
and the recent findings of another group appearing in the Proceedings of the
National Academy of Sciences, could force a rethinking of prevailing
theories that suggest germ cells have genetically programmed fates.

Instead, germ cells may be "a blank slate that await chemical instructions
to tell them which way to go," Science study coauthor Peter Koopman at the
University of Queensland in Brisbane told The Scientist.

Whether developing germ cells become male or female depends on when they
enter meiosis. If meiosis begins during fetal development, oogenesis is
triggered, while delayed meiosis spurs spermatogenesis. It is widely thought
that fetal germ cells in both males and females are intrinsically programmed
to enter meiosis and trigger oogenesis unless prevented from doing so by a
meiosis-inhibiting factor in males that until now had not been identified,
Koopman said.

Koopman and his colleagues screened for genes expressed in a sex-specific
manner during mouse gonadogenesis and focused on Cyp26b1, the product of
which degrades retinoic acid, which in turn regulates the development of
many organ systems. Quantitative reverse transcription polymerase chain
reaction (RT-PCR) analysis showed that expression of the gene became
male-specific about 12.5 days post coitum.

Koopman and his colleagues found that in male Cyp26b1-knockout mice, germ
cells enter meiosis precociously, suggesting CYP26B1 is the
meiosis-inhibiting factor in male embryos. The PNAS study similarly found
Cyp26b1 is expressed in embryonic mouse testes but not in ovaries, and that
an inhibitor of CYP26 enzymes induced expression of pre-meiotic marker Stra8
in the testes. CYP26B1 is the only CYP26 enzyme found in embryonic gonads.

In quantitative RT-PCR experiments, Koopman and his colleagues found
exposing male urogenital ridge organ cultures to retinoic acid induced the
expression of Stra8 and meiotic progression markers Scp3 and Dmc1, while
suppressing the pluripotency marker Oct4. Exposing female urogenital ridge
organ cultures to a retinoic acid receptor antagonist prevented the
downregulation of Oct4 normally observed in fetal ovaries and substantially
decreased Stra8, Scp3 and Dmc1 expression, suggesting retinoic acid is a
meiosis-inducing factor. The PNAS study likewise found retinoic acid
stimulated Stra8 expression in embryonic mouse testes.

Full text at TheScientist
http://www.the-scientist.com/news/display/23260/

Posted by
Robert Karl Stonjek


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