Abstract
Current evidence indicates that rises in systemic levels of estrogen create in the
uterus an inhibitory environment for sympathetic nerves. However, molecular insights
of these changes are far from complete. We evaluated if semaphorin 3F mRNA, a sympathetic
nerve repellent, was produced by the rat uterus and if its expression was modulated
by estrogen. We also analyzed whether uterine nerves express the semaphorin 3F binding
receptor, neuropilin-2. Uterine levels of semaphorin 3F mRNA were measured using real
time reverse transcriptase–polymerase chain reaction in prepubertal rat controls and
following chronic estrogen treatment. Localization of semaphorin 3F transcripts was
determined by in situ hybridization and the expression of neuropilin-2 was assessed
by immunohistochemistry. These studies showed that: (1) chronic estrogen treatment
led to a 5-fold induction of semaphorin 3F mRNA in the immature uterus; (2) estrogen
provoked a tissue-specific induction of semaphorin 3F which was particularly localized
in the connective tissue that borders muscle bundles and surrounds intrauterine blood
vessels; (3) two major cell-types were recognized in the areas where transcripts were
concentrated, fibroblast-like cells and infiltrating eosinophil leukocytes; and (4)
some delicate nerve terminal profiles present in the estrogenized uterus were immunoreactive
for neuropilin-2. Temporal and spatial expression patterns of semaphorin 3F/neuropilin-2
are consistent with a possible role of this guidance cue in the remodeling of uterine
sympathetic innervation by estrogen. Though correlative in its nature, these data
support a model whereby semaphorin 3F, in combination with other inhibitory molecules,
converts the estrogenized myometrium to an inhospitable environment for sympathetic
nerves.
Keywords
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Article info
Publication history
Published online: July 04, 2011
Accepted:
June 8,
2011
Received in revised form:
May 2,
2011
Received:
October 24,
2010
Identification
Copyright
© 2011 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
