Maternal smoking is an avoidable source of fetal exposure to 1,000s of toxicants in many pregnancies (20% in Scotland). It is associated with poor pregnancy outcome (such as low birth weight) and risk of illness later in life such as metabolic syndrome. More than half of pregnant women are overweight or obese which also impacts on pregnancy outcome and long-term health of the offspring (including diabetes and obesity). Although mechanistic links between these maternal factors and fetal consequences have not been fully elucidated, they may involve changes in placental gene and protein expression. This thesis uses cohorts of human fetal tissue and placentas from 1st and 2nd trimester, normally progressing pregnancies, and placentas from term. Using RT-qPCR and targeted proteomics, I uncovered expression changes of vital transporters and receptors in the placenta that associated with smoke-exposure and maternal obesity which was often fetal-sex specific. Maternal smoking influenced both genetic and protein expression of transporters including the major iron placental uptake transporter (TFRC). Smoke-exposure was also associated with reduced ability of the female placenta to cleave oxytocin (LNPEP) and reduce inflammation (Annexin-1). High maternal BMI associated with hyperglycaemic fetal plasma, upregulated INS-Rin male placentas and increased GLUT1 and LAT4 expression at term. Further, I investigated serotonin metabolism in the placenta, fetal brain and liver as a process potentially influenced by maternal BMI. Both gene expression and activity of the serotonin inactivating enzyme was downregulated in the fetal brain of high BMI mothers. This thesis characterises the placental plasma membrane proteome across all 3 trimesters of pregnancy, allowing unique insight into which transporters and receptors play critical roles in nutrient transfer and signalling in the placenta. Further, these findings may be potential pathways by which the offspring of smoke-exposed or high BMI pregnancies experience altered fetal programming.