Postnatal peripheral inflammatory challenge alters expression of ovarian signalling pathway - implications for impaired reproductive development. (#269)
We have recently reported neonatal exposure to an inflammatory challenge by administration of lipopolysaccharide (LPS) produces long-term alterations in reproductive development in the female Wistar rat. Activation of the immune response has been suggested to underlie these effects. Our current aim is to identify the cellular mechanisms that lead to the previously documented impaired ovulation and reduced oocyte development. On postnatal days (PNDs) 3 and 5 (birth=PND1) whole litters were treated with either 0.05mg/kg of LPS (Salmonella Enteritidis) or an equivalent volume of non-pyrogenic saline. On PND 7 female pups were sacrificed and ovaries obtained. Total RNA was extracted using the RNeasy Mini kit (Qiagen) and microarray analysis was completed using Agilent SurePrint G3 Rat GE 8x60K Microarray. Microarray analysis revealed 712 genes were differentially regulated (2-fold change; p<.05) in the ovaries of LPS-treated animals. Ingenuity Pathway Analysis of the differentially regulated genes implicated ovarian signalling pathways associated with an inflammatory response, tissue development and reproductive system disease, with several canonical pathways activated in response to LPS treatment involved in immune recognition, such as NF-kB activation and LPS-stimulated MAPK signalling. The expression of the top differentially regulated genes, including ZFPM2 (7.6 fold), NPPC (7.16 fold), PTGER3 (4.190 fold), DHFR (3.92 fold) and ITPR2 (3.9 fold) will be confirmed by qRT-PCR. Our preliminary data suggest marked sensitivity of neonatal gonads to an inflammatory challenge, the impact of which subsequently has profound implications for female fertility.