Neonatal immune challenge by administration of lipopolysaccharide (LPS) produces enduring alterations in the development and activity of neuroendocrine, immune and other physiological systems. We have recently reported that neonatal exposure to an immune challenge by administration of LPS results in altered reproductive development in the female Wistar rat. Specifically, LPS-treated animals exhibited diminished ovarian reserve and altered reproductive lifespan. In the current study, we examined the cellular mechanisms that lead to the previously documented impaired ovulation and reduced follicular pool. Rats were administered intraperitoneally either 0.05 mg/kg of LPS (Salmonella Enteritidis) or an equivalent volume of non-pyrogenic saline on postnatal days (PNDs) 3 and 5, and ovaries were obtained on PND 7. Microarray analysis revealed a significant upregulation in transcript expression (2-fold change; p < 0.05) for a substantial number of genes in the ovaries of LPS-treated animals, implicated in immune cell signaling, inflammatory responses, reproductive system development and disease. Several canonical pathways involved in immune recognition were affected by LPS treatment, such as nuclear factor-κB (NF-κB) activation and LPS-stimulated mitogen-activated protein kinase (MAPK) signaling. Quantitative Real-time PCR analysis supported the microarray results. Protein expression analysis of several components of the MAPK signaling pathway revealed a significant upregulation in the expression of Toll-like receptor 4 (TLR4) in the neonatal ovary of LPS-treated animals. These results indicate that neonatal immune challenge by administration of LPS has a direct effect on the ovary during the sensitive period of follicular formation. Given the pivotal role of inflammatory processes in the regulation of reproductive health, our findings suggest that early life immune activation via TLR signaling may have significant implications for the programming of ovarian development and fertility.
Keywords: LPS, TLR4, MAPK, neonatal, immune challenge, reproductive development
Citation: Sominsky L, Sobinoff AP, Jobling MS, Pye V, McLaughlin EA and Hodgson DM (2013) Immune regulation of ovarian development: programming by neonatal immune challenge. Front. Neurosci. 7:100. doi: 10.3389/fnins.2013.00100
Received: 28 February 2013; Accepted: 22 May 2013;
Published online: 12 June 2013.
Edited by:Quentin Pittman, University of Calgary, Canada
Reviewed by:Oline K. Ronnekleiv, Oregen Health and Science University, USA
Copyright © 2013 Sominsky, Sobinoff, Jobling, Pye, McLaughlin and Hodgson. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Luba Sominsky, School of Psychology, Behavioural Sciences Building, The University of Newcastle, University Drive, Callaghan, NSW 2308, Australia e-mail: firstname.lastname@example.org