Serotonin (5-HT) is one of the neurotransmitters involved in mood regulation and has been implicated in the development of mood and anxiety disorders. Serotonin transporters (SERT) facilitate the transfer of serotonin into neurons; serotonin reuptake inhibitor (SSRI) antidepressants bind to these transporters and appear to exert their effect on mood by inhibiting the reuptake of serotonin and thus increasing the levels of this neurotransmitter at the synapse.
Serotonin is also present in the female reproductive organs of various species, including humans (Amenta et al, 1992, Il’kova et al, 2004, Amireault et al, 2005a, Sosa et al, 1988, Bodis et al, 1992a). Different serotonin receptor subtypes exist in human oocytes (Nelson et al, 2000) and granulosa cells (Graveleau et al, 2000), the cells surrounding the growing oocyte. Serotonin transporters have also been detected in mouse oocytes and early embryos (Amireault et al, 2005a).
In serotonin receptor knockout mice, genetically engineered so that the gene encoding for the serotonin receptor has been inactivated or “knocked out”, fertility and early embryonic development appear to be unaffected. However, in knockout mice lacking tryptophan hydroxylase or TPH, an enzyme essential for the synthesis of serotonin, there was a reduction in the size of the embryos, suggesting that serotonin may play an important role in early embryonic development (Cote et al, 2007).
In other studies, the addition of serotonin to human granulosa cells leads to the production of progesterone and estrogen (Bodis et al, 1992b, Graveleau et al, 2000, Koppan et al, 2004). In a mouse model, depleting serotonin prior to gestation (day 0 to day 5) results in the inability to reproduce (Acharya et al, 1989). On the other hand, the addition of serotonin during the pre-implantation stage leads to a reduction in the number of cells in the developing embryo (Ilkova et al, 2004, Vesela et al, 2003).
Taken together, these studies confirm that serotonin plays an important role in oocyte maturation and the early stages of embryonic development. Hence, one could hypothesize that the appropriate regulation of maternal serotonin levels is crucial to ensure fertility and normal embryonic development. These studies may also lend support to the finding that mothers with depression, who presumably have some degree of serotonergic dysregulation, are more likely to have low birth weight infants.
Thus far, no studies have explored how SSRIs may influence oocyte maturation, fertilization, implantation, or early embryonic development. Future studies are clearly needed to clarify the roles of serotonin and the potential effects of SSRIs on early embryonic development.
Snezana Milanovic, M.D., M.Sc
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Great article. Lots of implications for fertility, & miscarriage.