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10 October 2017 Neonatal immune activation depletes the ovarian follicle reserve and alters ovarian acute inflammatory mediators in neonatal rats
Erin A. Fuller, Luba Sominsky, Jessie M. Sutherland, Kate A. Redgrove, Lauren Harms, Eileen A. McLaughlin, Deborah M. Hodgson
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Abstract

Normal ovarian development is crucial for female reproductive success and longevity. Interruptions to the delicate process of initial folliculogenesis may lead to ovarian dysfunction. We have previously demonstrated that an early life immune challenge in the rat, induced by administration of lipopolysaccharide (LPS) on postnatal day (PND) 3 and 5, depletes ovarian follicle reserve long term. Here, we hypothesized that this neonatal immune challenge leads to an increase in peripheral and ovarian inflammatory signaling, contributing to an acute depletion of ovarian follicles. Morphological analysis of neonatal ovaries indicated that LPS administration significantly depleted PND 5 primordial follicle populations and accelerated follicle maturation. LPS exposure upregulated circulating interleukin 6, tumor necrosis factor alpha (TNFa), and C-reactive protein on PND 5, and upregulated ovarian mRNA expression of Tnfa, mitogen-activated protein kinase 8 (Mapk8/Jnk1), and growth differentiation factor 9 (Gdf9) (P < 0.05).Mass spectrometry and cell signaling pathway analysis indicated upregulation of cellular pathways associated with acute phase signaling, and cellular survival and assembly. Apoptosis assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling indicated significantly increased positive staining in the ovaries of LPS-treated neonates. These findings suggest that increased proinflammatory signaling within the neonatal ovary may be responsible for the LPS-induced depletion of the primordial follicle pool. These findings also have implications for female reproductive health, as the ovarian reserve is a major determinate of female reproductive longevity.

Summary Sentence

Neonatal immune activation acutely impacts immune-mediated early ovarian development, depleting the primordial follicle pool and upregulating inflammatory mediators.

© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Erin A. Fuller, Luba Sominsky, Jessie M. Sutherland, Kate A. Redgrove, Lauren Harms, Eileen A. McLaughlin, and Deborah M. Hodgson "Neonatal immune activation depletes the ovarian follicle reserve and alters ovarian acute inflammatory mediators in neonatal rats," Biology of Reproduction 97(5), 719-730, (10 October 2017). https://doi.org/10.1093/biolre/iox123
Received: 10 May 2017; Accepted: 7 October 2017; Published: 10 October 2017
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KEYWORDS
cytokines
developmental origins of health and disease
early life immune stress
follicular development
Inflammation
lipopolysaccharide
oocyte development
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