INVESTIGADORES
HALPERIN Julia
congresos y reuniones científicas
Título:
PRAP/17β-Hydroxysteroid Dehydrogenase Type 7 Gene Plays a Crucial Role in Embryonic Development and Fetal Survival.
Autor/es:
AURORA SHEH, JIFANG MAO, GIL GIBORI, JULIA HALPERIN, JAMIE LE, HIROAKI KIYOKAWA AND GEULA GIBORI
Lugar:
Evanston, USA
Reunión:
Simposio; 28th Annual Minisymposium on Reproductive Biology; 2007
Institución organizadora:
Northwestern University
Resumen:
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Our laboratory has previously cloned and
purified a novel 17β-HSDenzyme, (PRAP/17β-HSD7) which is highly expressed in
the corpus luteum of the ovary and converts estrone to estradiol. To examine the functional significance of
PRAP/17β-HSD7in pregnancy, we generated a knockout mouse model with a deletion
of the PRAP/17β-HSD7gene. We anticipated
a mouse with severe fertility defect due to its inability to regulate estrogen
levels during pregnancy in the absence of this enzyme. The heterozygous mutant mice (PRAP/17β-HSD7+/-)
appeared normal in their development and gross anatomy. They were born with the expected Mendelian
frequency from F1 parents and grew to adulthood. They were fertile as indicated by normal
estrus cycle, by their ability to become pregnant and by the size of the
litter. In addition, no difference was
observed at both mRNA and protein levels of PRAP/17β-HSD7between the postpartum
ovaries of heterozygous and their wild type littermates. To our surprise, the
breeding of heterozygous mice yielded no viable PRAP/17β-HSD7null mice. However, we found PRAP/17β-HSD7null embryo in
utero at day 8.5 and 9.5 of gestation.
These embryos were dramatically smaller in size and displayed severe
disorganization of blood vessels as compared to heterozygous and wild type
embryos. The null embryos were found in utero until day 11.5 with severe
resorption. The cause of this early
lethality is unknown, as there is no known function of fetal steroids at
embryonic day 8.5. However this gene is expressed in the placenta where we show
that estradiol plays an important role in vascularization and in the early
development of the fetus. Recent reports
have shown that PRAP/17β-HSD7also participates in cholesterol
biosynthesis. Since cholesterol is known
to be essential for normal fetal development, PRAP/17β-HSD7 may also play a
role early in development through this pathway. This is the first discovery
identifying a role for PRAP/17β-HSD7gene in early mouse development and raises
important questions regarding the role and significance of this genes function.
