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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)719-730
Number of pages12
JournalBiology of Reproduction
Volume97
Issue number5
DOIs
Publication statusPublished - 1 Nov 2017
Externally publishedYes

Fingerprint

Ovarian Follicle
Lipopolysaccharides
Ovary
Growth Differentiation Factor 9
Lymphotoxin-beta
Mitogen-Activated Protein Kinase 8
DNA Nucleotidylexotransferase
Reproductive Health
C-Reactive Protein
Interleukin-6
Mass Spectrometry
Up-Regulation
Tumor Necrosis Factor-alpha
Ovarian Reserve
Apoptosis
Staining and Labeling
Messenger RNA
Population

Cite this

Fuller, E. A., Sominsky, L., Sutherland, J. M., Redgrove, K. A., Harms, L., McLaughlin, E. A., & Hodgson, D. M. (2017). Neonatal immune activation depletes the ovarian follicle reserve and alters ovarian acute inflammatory mediators in neonatal rats. Biology of Reproduction, 97(5), 719-730. https://doi.org/10.1093/biolre/iox123
Fuller, Erin A. ; Sominsky, Luba ; Sutherland, Jessie M. ; Redgrove, Kate A. ; Harms, Lauren ; McLaughlin, Eileen A. ; Hodgson, Deborah M. / Neonatal immune activation depletes the ovarian follicle reserve and alters ovarian acute inflammatory mediators in neonatal rats. In: Biology of Reproduction. 2017 ; Vol. 97, No. 5. pp. 719-730.
@article{ebfab19ede9b4bada9af4abd9114e3f3,
title = "Neonatal immune activation depletes the ovarian follicle reserve and alters ovarian acute inflammatory mediators in neonatal rats",
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.",
keywords = "Cytokines, Developmental origins of health and disease, Early life immune stress, Follicular development, Inflammation, Lipopolysaccharide, Oocyte development, Animals, Newborn, Rats, Wistar, Rats, Ovary/drug effects, Ovarian Follicle/physiology, Animals, Cytokines/genetics, Female, Lipopolysaccharides/toxicity",
author = "Fuller, {Erin A.} and Luba Sominsky and Sutherland, {Jessie M.} and Redgrove, {Kate A.} and Lauren Harms and McLaughlin, {Eileen A.} and Hodgson, {Deborah M.}",
year = "2017",
month = "11",
day = "1",
doi = "10.1093/biolre/iox123",
language = "English",
volume = "97",
pages = "719--730",
journal = "Biology of Reproduction",
issn = "0006-3363",
publisher = "Society for the Study of Reproduction",
number = "5",

}

Fuller, EA, Sominsky, L, Sutherland, JM, Redgrove, KA, Harms, L, McLaughlin, EA & Hodgson, DM 2017, 'Neonatal immune activation depletes the ovarian follicle reserve and alters ovarian acute inflammatory mediators in neonatal rats', Biology of Reproduction, vol. 97, no. 5, pp. 719-730. https://doi.org/10.1093/biolre/iox123

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

In: Biology of Reproduction, Vol. 97, No. 5, 01.11.2017, p. 719-730.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Neonatal immune activation depletes the ovarian follicle reserve and alters ovarian acute inflammatory mediators in neonatal rats

AU - Fuller, Erin A.

AU - Sominsky, Luba

AU - Sutherland, Jessie M.

AU - Redgrove, Kate A.

AU - Harms, Lauren

AU - McLaughlin, Eileen A.

AU - Hodgson, Deborah M.

PY - 2017/11/1

Y1 - 2017/11/1

N2 - 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.

AB - 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.

KW - Cytokines

KW - Developmental origins of health and disease

KW - Early life immune stress

KW - Follicular development

KW - Inflammation

KW - Lipopolysaccharide

KW - Oocyte development

KW - Animals, Newborn

KW - Rats, Wistar

KW - Rats

KW - Ovary/drug effects

KW - Ovarian Follicle/physiology

KW - Animals

KW - Cytokines/genetics

KW - Female

KW - Lipopolysaccharides/toxicity

UR - http://www.scopus.com/inward/record.url?scp=85043597703&partnerID=8YFLogxK

UR - http://www.mendeley.com/research/neonatal-immune-activation-depletes-ovarian-follicle-reserve-alters-ovarian-acute-inflammatory-media

U2 - 10.1093/biolre/iox123

DO - 10.1093/biolre/iox123

M3 - Article

VL - 97

SP - 719

EP - 730

JO - Biology of Reproduction

JF - Biology of Reproduction

SN - 0006-3363

IS - 5

ER -