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Abstract
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 pre-granulosa
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).
To determine if genistein treatment leads to MOFs by
inhibiting breakdown of
oocyte nests, mice were treated neonatally with genistein
(50 mg/kg/day) on
days 1-5 and the differentiation of the ovary 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.
Key words:
Environment
Mechanisms of Hormone Action
Ovary
Developmental biology
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