Reproduction Abstracts

Introduction: Normal function of the placenta, an essential conduit between mother and fetus, is crucial for a healthy pregnancy. Placental molecular transporters play essential gatekeeping roles, regulating the exchange of nutrients, gases, hormones and diverse molecules between the mother and developing fetus. Expression of some transporters change throughout pregnancy, which may alter fetal sensitivity to maternally-derived nutritional compounds, environmental contaminants (e.g. cigarette smoke chemicals) and medications. We characterised the expression of major molecular transporters in human placentas from late 1st to late 2nd trimester to understand how gestational age and/or fetal sex influence transporter expression.

Methods: Placental and fetal cDNA were genotyped to confirm sex of 48 placentas (8–18 weeks of gestation, male n=21, female, n=27, MRC/Wellcome Trust Human Developmental Biology Resource [www.hdbr.org]) from electively-terminated normal pregnancies. Transcripts of 49 major transporters were measured by real time qPCR and values normalised against validated house-keeping genes (NormFinder). Linear Regression models were used to analyse gestation- and/or sex-specific differences in placental transporter expression.

Results and Discussion: Transcripts for 31/49 transporters were detectable in the human placenta. No sex-specific expression patterns were observed, but 4 transporters changed with gestational age. The thyroid hormone transporter (SLCO4A1) expression decreased with gestational age reflecting the declining need for maternally-derived thyroid hormone. ABCG2, involved in drug/xenobiotic efflux, was highly expressed in earlier stages suggesting a need for protection during organogenesis. Prostaglandin transporter (SLCO2A1) expression increased, suggesting a role in controlling prostaglandin levels, important in maintaining pregnancy. SLC22A17 also increased, likely supporting nutritional transport and iron homeostasis. Overall, our results suggest that transporters relating to basal metabolic processes, nutrient delivery and drug resistance are stably expressed across gestation maintaining fetal nutrition and protection. Characterising differential transporter expression will improve understanding of critical windows of fetal vulnerability to drugs and toxicants.