172. A MODEST INFLAMMATORY INSULT IN THE PRE-IMPLANTATION PERIOD ALTERS OVIDUCT CYTOKINE EXPRESSION AND PROGRAMS FETAL DEVELOPMENT
P. Y. Chin A , J. G. Thompson A and S. A. Robertson AObstetrics and Gynaecology, University of Adelaide, Adelaide, SA, Australia.
Reproduction, Fertility and Development 22(9) 90-90 https://doi.org/10.1071/SRB10Abs172
Published: 6 September 2010
Abstract
The cytokine milieu surrounding the pre-implantation embryo contributes to programming optimal embryo development. Perturbations to the maternal environment such as infection and inflammation during the pre-implantation period can influence cytokine synthesis and may cause changes in embryo development that compromise pregnancy outcome. We aimed to investigate the effect of an inflammatory insult with LPS during the pre-implantation period on later fetal development and the role of oviduct cytokine expression in mediating this response. LPS (at various doses of 0.5–62.5 μg) was administered i.p. to C57Bl/6 mice on both day 3 and day 4 post coitum (pc). The effects of treatment on day 4 blastocysts and day 18 fetal development were analysed. Blastocysts from LPS-treated mothers showed reduced viability and smaller total cell number, but were only significant when doses of >12.5 μg LPS were administered. This was not a direct effect of LPS, as no effect of LPS on embryo development in vitro was seen, even at very high LPS concentrations (25 μg/mL). At day 18 pc, pregnancy rates and the number of viable fetuses, as well as fetal and placenta weights were all reduced after low dose LPS treatment (0.5 μg) compared to control PBS-treated females. qPCR analysis of day 4 oviduct tissue revealed that administration of 12.5ug of LPS resulted in increased mRNA expression of cytokines including IL6, TNFA, IL1B, IFNG, IL10 and LIF. Our findings show that a modest pro-inflammatory insult with LPS in the pre-implantation period programs the embryo for later adverse effects on fetal and placental development. The effects of LPS appear to be mediated indirectly via the maternal tract, and altered oviduct cytokine expression which impairs pre-implantation embryo development is implicated as the underlying mechanism. This model will now be utilised to investigate the potential role of specific inflammatory cytokines TNFA and IFNG in mediating this response.
