Endocrine Abstracts

Introduction: The placenta interchanges nutrients, oxygen and waste between mother and fetus, acts as a gate-keeper to protect the fetus and creates an optimal endocrine environment to maintain the pregnancy. Placental insufficiency underpins common pregnancy complications (e.g. intrauterine growth restriction, preterm birth). Perturbed expression of molecular transporter proteins in the placental syncytiotrophoblast will affect fetal exposure to harmful drugs/xenobiotics such as those in cigarette smoke. We therefore aimed to investigate the effect of maternal smoking on molecular transporters involved in trans-placental and fetal hepatic transport.

Methods: Placenta and fetal liver (same pregnancies) were extracted and sexed (8–18 weeks of gestation, MRC/Wellcome Trust Human Developmental Biology Resource [www.hdbr.org]) from electively-terminated normal pregnancies. About 49 transporter transcripts and mitochondrial DNA markers were quantified by real-time qPCR using a stable combination of house-keeping genes. Linear regression models were used to determine (1) sex and/or age-specific changes to transporter expression and (2) whether maternal smoking (confirmed using the nicotine metabolite, cotinine), perturbed these patterns.

Results & Conclusions: About 28/49 transporter transcript levels changed with gestational age in the liver and/or placenta (e.g. thyroid hormone transporter). Key transporters were effected by smoking (11, e.g. folate transporter) and/or fetal sex (9, e.g. drug resistance transporter). The fetal liver was more sexually dimorphic and more perturbed by smoke exposure (9 transcripts affected compared to 2 in the placenta). SLC22A2, a cationic drug eliminator, increased with age in placentas of smoke-exposed fetuses. SLC22A18, a candidate tumour suppressor (substrate unknown), was decreased in smoke-exposed female placenta suggesting sex-specific responses to stress. However, mitochondrial DNA content in both organs was unaffected by smoking suggesting that disruption of transporter ontogeny was preceding wider damage. A better understanding of these expression profiles is vital to recognise periods of increased placental and fetal hepatic permeability to maternally-derived chemicals, such as medications, pollutants or cigarette smoke.