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Neonatal genistein treatment alters
ovarian differentiation in the mouse: inhibition of oocyte nest
breakdown and increased oocyte survival
Jefferson W, Newbold R, Padilla-Banks E, Pepling
M
Developmental Endocrinology and Endocrine Disruptor Section,
Laboratory of Molecular Toxicology, National Institute of
Environmental Health Sciences, NIH/DHHS, Research Triangle Park, North
Carolina 27709.
Early in ovarian differentiation, female mouse germ cells develop in
clusters called oocyte nests or germline cysts.
After birth, mouse germ cell nests break down into individual oocytes
that are surrounded by somatic pregranulosa cells to form primordial
follicles.
Previously, we have shown that mice treated neonatally with genistein,
the primary soy phytoestrogen, have multi-oocyte follicles (MOFs), an
effect apparently mediated by estrogen receptor 2 (ESR2, more commonly
known as ERbeta).
To determine if genistein treatment leads to MOFs by inhibiting
breakdown of oocyte nests, mice were treated neonatally with genistein
(50 mg/kg per day) on Days 1-5, and the differentiation of the ovary
was compared with untreated controls.
Mice treated with genistein had fewer single oocytes and a higher
percentage of oocytes not enclosed in follicles.
Oocytes from genistein-treated mice exhibited intercellular bridges at
4 days of age, long after disappearing in controls by 2 days of
age.
There was also an increase in the number of oocytes that survived
during the nest breakdown period and fewer oocytes undergoing
apoptosis on Neonatal Day 3 in genistein-treated mice as determined by
poly (ADP-ribose) polymerase (PARP1) and deoxynucleotidyl transferase
mediated deoxyuridine triphosphate nick end-labeling (TUNEL).
These data taken together suggest that genistein exposure during
development alters ovarian differentiation by inhibiting oocyte nest
breakdown and attenuating oocyte cell death.
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