Neonatal Exposure to Estradiol Valerate Programs Ovarian Sympathetic Innervation and Follicular Development in the Adult Rat
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2008-04Metadata
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Sotomayor Zárate, Ramón
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Neonatal Exposure to Estradiol Valerate Programs Ovarian Sympathetic Innervation and Follicular Development in the Adult Rat
Abstract
A single injection of estradiol valerate (EV) to 14-day-old rats
(when the ovarian follicle population has been already established)
disrupts cyclicity, increases the activity of key enzymes of
androgen biosynthesis, and develops polycystic ovary by a
causally related increase in ovarian noradrenaline (NA). The
current study examined an early window of ovarian development
to look for a specific stage of development at which
estradiol can induce such changes in sympathetic activity and
follicular development. A single dose of EV applied to rats before
the first 12 h of life rapidly increases (after 24 h) the ovarian
expression of nerve growth factor (Ngfb) and p75 low-affinity
neurotrophic receptor (Ngfr) mRNAs. When adults, rats
presented early vaginal opening, disrupted cyclicity, appearance
of follicular cyst, absence of corpus luteum, and infertility. Total
follicles decreased, mainly due to a reduced number of
primordial follicles, suggesting that estradiol acts in the first
stages of folliculogenesis, when primordial follicles are organizing.
These changes paralleled a 6-fold increase in NA concentration.
No changes in NA content were found in the celiac
ganglia, suggesting a local, non-centrally mediated effect of
estradiol. Surgical section of the superior ovarian nerve (the
main source of sympathetic nerves to the ovary) to rats
neonatally treated with EV decreased intraovarian NA, delayed
vaginal opening, and blocked the development of follicular cyst
and that of preovulatory follicles. Therefore, we can conclude
that early exposure to estradiol permanently modifies ovarian
sympathetic activity and causes profound changes in follicular
development, leading to the polycystic ovary condition.
Patrocinador
Supported by Fondo Nacional de Desarrollo Cientı´fico y Tecnolo´ gico
(FONDECYT) grant 105-0765 to H.E.L. and grant PG/63/2005 to R.S.Z.
(Departamento de Postgrado y Postı´tulo, Universidad de Chile). R.S.Z.
is the recipient of a Ph.D. in Pharmacology fellowship UCH-208 from
the Mejoramiento de la Calidad y Equidad de la Educacio´n Superior
(MECESUP) Chilean Program.
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BIOLOGY OF REPRODUCTION, Volume: 78, Issue: 4, Pages: 673-680, 2008
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