Oral Presentation The International Congress of Neuroendocrinology 2014

Factors in early life programming of reproductive fitness (#99)

Deborah Hodgson 1
  1. University of Newcastle, Callaghan, NSW, Australia

One in every 15 females is infertile. Decreased female fecundity has been related to advanced maternal age but the increasing number of young women in this category suggests a more complex aetiology. Pelvic inflammatory disease and bacterial infections of the uterus are important causes of infertility in humans. However, more recently evidence points to the critical role of the early life environment. Our studies have demonstrated that acute exposure to bacteria early in life has a profound and long lasting impact on female reproductive development and fertility. Using a rodent model of neonatal inflammation; LPS administration of 0.05 mg/kg lipopolysaccharide (LPS, Salmonella enteritidis) via intraperitoneal microinjection on postnatal days 3 and 5 we have demonstrated that neonatal bacterial exposure is associated with altered hormonal profiles, advanced onset of puberty, diminished follicular reserve, advanced reproductive senescence, impaired sexual behaviour and reduced mating success. This is associated with significant upregulation of inflammatory genes in the developing ovary. Most notably, we have demonstrated a significant upregulation in the expression of Toll-like receptor 4 (TLR4) in the neonatal ovary. These findings suggest activation of the immune response during early life disrupts the ontogeny of reproductive function, inflicting deleterious effects upon adult mating success. Given the regulatory role of inflammatory processes in the establishment of reproductive health, our findings suggest that early life immune activation via TLR signaling may have substantial implications for the programming of reproductive fitness.  Such that the disposition to infertility may begin early in life and is associated with ovarian inflammation induced by peripheral immune activation.