Placental expression of the serotonin transporter (SERT) gene: associations with maternal overweight/obesity and neonatal anthropometry.

Objectives: We investigated the relationship between maternal pre-pregnancy body mass index (BMI) and expression of key serotonin-regulating genes (namely, metabolic enzymes, transmembrane transporters and receptors) in term placentas, including a possible moderating effect of glucose tolerance status (normal glucose tolerance (NGT) vs. gestational diabetes mellitus (GDM)). Associations between placental expression of serotonin-regulating genes and neonatal anthropometry were also explored.

Methods: The study included 105 women with overweight/obesity (OWO) and 111 women with normal-weight (NW), all giving birth at term by planned cesarean section. Placental tissue was collected from the fetal side using a standardized protocol. Expression of serotonin-regulating genes was quantified by RT-qPCR and/or ELISA.

Results: Pre-pregnancy OWO, GDM or their interaction were not associated with mRNA levels of tryptophan hydroxylase 1 (TPH1), monoamine-oxidase A (MAOA), organic cation transporter 3 (OCT3), and serotonin receptor 2A (HTR2A) in term placentas. However, mRNA levels of plasma membrane monoamine transporter (PMAT) were significantly upregulated in association with pre-pregnancy OWO, regardless of GDM status (p = 0.014). Furthermore, in women with NGT, but not in women with GDM, pre-pregnancy OWO was associated with decreased placental serotonin transporter (SERT) mRNA levels (p = 0.001), while placental SERT protein levels were increased in women with pre-pregnancy OWO and further elevated in women with concurrent GDM (p = 0.005). In addition, higher placental SERT mRNA levels negatively predicted birth weight and newborn length and, in women with NGT, partially mediated the association between pre-pregnancy BMI and birth weight.

Conclusion: The results show associations between maternal pre-pregnancy OWO and altered expression of high- and low-affinity serotonin transport genes (SERT and PMAT, respectively). Among the genes analyzed, SERT may play a role in linking maternal OWO to fetal growth. The results underscore the importance of further functional studies into the placental serotonin system in the context of maternal OWO.