Low dose LPS insult during pre-implantation period programs fetal development  — ASN Events

Low dose LPS insult during pre-implantation period programs fetal development  (#154)

Peck Y Chin 1 , Jeremy G Thompson 1 , Sarah A Robertson 1
  1. Robinson Research Institute and Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia

The cytokine milieu surrounding the early embryo is pivotal in programming optimal embryo development. Perturbations to the maternal environment including infection, stress and environmental toxins can influence oviduct and uterine cytokine synthesis. We hypothesise that altered cytokine signals resulting from a proinflammatory LPS challenge in the pre-implantation period elicit change in the embryo developmental trajectory that in turn alter fetal growth and postnatal health. Our earlier work on the effects of peri-conceptual low dose LPS treatment in wildtype C57Bl/6 and mice with a null mutation in the Il10 gene (IL10-/- mice) revealed that the number of viable fetuses and fetal weight were both significantly reduced after LPS treatment, particularly in the IL10-/- mice. To understand the mechanism by which LPS treatment acts on the pre-implantation embryo, embryo transfer was utilised where day 3.5pc embryos from donors treated with LPS (25 ng/g) or PBS on days 2.5 and 3.5pc were transferred into pseudopregnant Swiss female recipients. When pregnancy parameters were evaluated at day 17.5pc, fetal weight was reduced by 16% and fetal:placental weight ratio was reduced by 25% in implantations resulting from embryos of LPS-treated donors compared to control donors. To further investigate the effect of peri-conceptual low dose LPS, postnatal growth and body morphometry analysis determined by DEXA scanning was quantified in male and female offspring from control and LPS-treated wildtype and IL10-/- females, until 19 weeks. LPS treatment caused delayed postnatal growth in male offspring from LPS-treated wildtype mothers compared to control male offspring, and central fat deposition was diminished. Our findings show that a modest inflammatory insult during the pre-implantation period programs the embryo for later adverse effects on fetal and placental development and that this effect is associated with the cytokine effects on the embryo as opposed to altered receptivity of the maternal reproductive tract.