Serotonin and Its Antidepressant-Sensitive Transport in Mouse Cumulus-Oocyte Complexes and Early Embryos Amireault P et al .
Serotonin (5-hydroxytryptamine, 5-HT), a neurohormone found in various non-neural tissues, including the gonads of many invertebrates, regulates spawning and oocyte meiotic maturation. The possibility that a local serotonergic network might also exist in the female gonads of vertebrate species, including mammals, remains poorly documented. To clarify this possibility, we investigated mouse cumulus cells, oocytes and embryos for 3 key serotonergic components, namely 5-HT itself, the rate-limiting enzyme for its production, tryptophan hydroxylase 1 (TPH1), and the 5-HT-specific transporter (SERT) required for modulating its cellular effects. Using a combination of reverse transcription-polymerase chain reaction analysis and immunofluorescence confocal microscopy, we showed that mouse cumulus cells, oocytes and embryos contain 5-HT and SERT, while only cumulus cells possess the 5-HT-producing enzyme TPH1 and may thus be the local source of 5-HT observed in other cells. With a semi-quantitative assay in single cells, we demonstrated that 5-HT can actively be taken up by isolated oocytes when it is supplied exogenously in vitro. This 5-HT transport in isolated oocytes is driven by a classical SERT, expressed up to the blastocyst stage, that is sensitive to the antidepressants fluoxetine and fluvoxamine, that belong to the selective serotonin reuptake inhibitor family. Altogether, our results show that 5-HT may be produced locally by cumulus cells and that it can be actively taken up by mammalian oocytes and embryos, as part of a likely larger serotonergic network possibly regulating various developmental processes much earlier than previously thought.