Pathway of Maternal Serotonin to the Human Embryo and Fetus

Abstract

Serotonin [5-hydroxytryptamine (5-HT)] is essential to intrauterine development, but its source is debated. We used immunocytochemistry to gauge 5-HT, its biosynthetic enzyme tryptophan hydroxylase 1 (TPH1); an importer (serotonin transporter, 5-HTT/SERT/SLC6A); other transporters [P-glycoprotein 1 (P-gp/ABCB1), OCT3/SLC22A3, and gap junction connexin-43]; and the 5-HT degradative enzyme monoamine oxidase A (MAOA) in sections of placentas. In humans, 5-HT was faintly stained only in first-trimester trophoblasts, whereas TPH1 was not seen at any stage. SERT was expressed in syncytiotrophoblasts and, more strongly, in cytotrophoblasts. MAOA was prominent in syncytiotrophoblasts, OCT3 and gap junctions were stained in cytotrophoblasts, and P-gp was present at the apical surfaces of both epithelia. 5-HT added to cultured placental explants accumulated in the trophoblast epithelium and reached the villus core vessels. Trophoblast uptake was blocked by the SERT inhibitor escitalopram. Inhibition of gap junctions with heptanol prevented the accumulation of 5-HT in cytotrophoblasts, whereas blocking OCT3 with decynium-22 and P-gp with mitotane led to its accumulation in cytotrophoblasts. Reducing 5-HT destruction by inhibiting MAOA with clorgyline increased the accumulation of 5-HT throughout the villus. In the mouse fetus, intravascular platelets stained prominently for 5-HT at day 13.5, whereas the placenta and yolk sac endoderm were both negative. TPH1 was not detected, but SERT was prominent in these mouse tissues. We conclude that serotonin is conveyed from the maternal blood stream through syncytiotrophoblasts, cytotrophoblasts and the villus core to the fetus through a physiological pathway that involves at least SERT, gap junctions, P-gp, OCT3, and MAOA.

TPH2 Deficiency Influences Neuroplastic Mechanisms and Alters the Response to an Acute Stress in a Sex Specific Manner

“…Since in adulthood it cannot pass the blood-brain barrier, these two enzymes define two 5-HT systems with independent regulation and different function. Although in the adult brain 5-HT is produced only by serotonergic neurons in raphe nuclei, during development there are other sources of this monoamine, including maternal 5-HT, that is actively transported through the placental brush border cells via the serotonin transporter (SERT; Cool et al, 1990 ; Carrasco et al, 2000 ; Kliman et al, 2018 ). Moreover, until postnatal day (pnd) 12, the blood-brain barrier is immature (Ribatti et al, 2006 ) and 5-HT, produced by TPH1 starting at embryonic day 14 in rodents (Côté et al, 2007 ) can reach the brain.…”

An experimental test of the ovulatory homolog model of female orgasm

“…Immunohistochemistry. Immunohistochemistry was performed as previously described (55), with the following modifications. Antigen retrieval was performed with a Cusinart model STM-1000 steamer.…”

Metformin from mother to unborn child – Are there unwarranted effects?

“…Even though mouse embryonic stem cells (mESCs) do express OCTs, mouse embryos express OCT1 at almost negligible levels and OCT3, MATE1/2 and PMAT at a much lower level than maternal liver [ 15 ]. SERT expression was found to be present in mouse placental and yolk sac tissues but also with diffused expression [ 16 ]. Additionally, mESCs have significantly fewer mitochondria with immature cristae [ 17 ].…”

“…However, there is currently no data on the expression of OCTs, MATE1/2 and PMAT in human embryonic and foetal tissues. SERT expression was found in human placental tissues but no data is available on human foetal tissues [ 16 ]. Therefore, the extent of metformin uptake and exposure in embryonic and foetal tissues is still unclear.…”