93. Acute neonatal immune challenge: Implications for the programming of later life female sub-fertility

• Published in: Brain, behavior, and immunity behavior, and immunity, 2014-09, Vol.40, p.e27-e27
• Main Authors: Fuller, E.A, Sominsky, L, Rolfe, K.T, Sutherland, J.M, McLaughlin, E.A, Hodgson, D.M
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Psychiatry
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2014.06.113

Infertility and sub-fertility is increasing in women of a healthy reproductive age, suggesting a complex aetiology in which the early life environment may play an important role. The fundamentals for reproductive success are established during early development, regulated by immune-endocrine pathways. Thus, immune disturbances during critical periods may dictate later life reproductive health. We have established that a neonatal immune challenge with lipopolysaccharide (LPS) induces long-term reproductive alterations, including altered hormonal profiles, impaired gonadal morphology, and sexual behaviour deficits. Importantly, we have shown neonatal LPS activates molecular inflammatory pathways in the developing ovary. The current study examines the acute effects of neonatal LPS exposure on the developing ovary and the programming effects of this challenge on adult sexual behaviour and motivation. Female Wistar rats were administered with LPS or saline (0.05 mg/kg, IP) on postnatal days (PNDs) 3 and 5. Plasma levels of interleukin-6 and C-reactive protein were assessed on PND5. Ovaries were immunohistochemically stained for morphological analysis and markers of apoptosis. LPS exposure resulted in significant increases in plasma proinflammatory markers, a decrease in total numbers of ovarian primordial follicles, and increased apoptosis in the neonatal ovary. Preliminary observations of adult sexual behaviour suggest neonatally-treated females exhibit altered sexual motivation. The current study indicates neonatal peripheral inflammation has an acute detrimental effect on ovarian development, resulting in the long-term programming of reproductive fitness.