Nutrient transporter expression in both the placenta and fetal liver are affected by maternal smoking

Natasha Walker,Panagiotis Filis,Peter J O'Shaughnessy,Michelle Bellingham,Paul A Fowler

doi:10.1016/j.placenta.2019.02.010

Abstract

IntroductionThe placenta controls nutrient transfer between mother and fetus via membrane transporters. Appropriate transplacental passage of nutrients is essential for fetal growth and development. We investigated whether transporter transcript levels in human placenta-liver pairs from first and early second trimester pregnancies exhibit gestational age- or fetal sex-specific profiles and whether these are dysregulated by maternal smoking. MethodsIn a step-change for the field, paired placenta and fetal livers from 54 electively terminated, normally-progressing pregnancies (7–20 weeks of gestation, Scottish Advanced Fetal Research Study, REC 15/NS/0123) were sexed and cigarette smoking-exposure confirmed. Thirty-six nutrient transporter transcripts were quantified using RT-qPCR. ResultsWhile fetal, liver and placenta weights were not altered by maternal smoking, levels of transporter transcripts changed with fetal age and sex in the placenta and fetal liver and their trajectories were altered if the mother smoked. Placental levels of glucose uptake transporters SLC2A1 and SLC2A3 increased in smoking-exposed fetuses while smoking was associated with altered levels of amino acid and fatty acid transporter genes in both tissues. SLC7A8, which exchanges non-essential amino acids in the fetus for essential amino acids from the placenta, was reduced in smoking-exposed placentas while transcript levels of four hepatic fatty acid uptake transporters were also reduced by smoking. DiscussionThis data shows that fetal sex and age and maternal smoking are associated with altered transporter transcript levels. This could influence nutrient transport across the placenta and subsequent uptake by the fetal liver, altering trophic delivery to the growing fetus.

Highlights

The placenta controls nutrient transfer between mother and fetus via membrane transporters
Since fetal nutrient demand is not met by diffusion alone, nutrient availability in the fetal compartment is dependent on appropriate expression profiles of placental membrane transporters in the syncytiotrophoblast and fetal capillaries
The collection of human fetal material was approved by the National Health Service (NHS) Grampian Research Ethics Committees (REC 15/NS/0123)

Summary

Introduction

The placenta controls nutrient transfer between mother and fetus via membrane transporters. We investigated whether transporter transcript levels in human placenta-liver pairs from first and early second trimester pregnancies exhibit gestational age- or fetal sex-specific profiles and whether these are dysregulated by maternal smoking. Discussion: This data shows that fetal sex and age and maternal smoking are associated with altered transporter transcript levels. This could influence nutrient transport across the placenta and subsequent uptake by the fetal liver, altering trophic delivery to the growing fetus. Transplacental transfer of amino acids, fatty acids, glucose and cholesterol, essential nutrients for fetal development, is mediated by well-characterised syncytial membrane transporters in the human placenta (Fig. 1). Characterising these patterns of expression and how they can be changed by maternal factors is important to better understand how modifiable maternal lifestyle can influence placental function and fetal development

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Conclusion