From Implantation to Birth: Insight into Molecular Melatonin Functions

Abstract

Melatonin is a lipophilic hormone synthesized and secreted mainly in the pineal gland, acting as a neuroendocrine transducer of photoperiodic information during the night. In addition to this activity, melatonin has shown an antioxidant function and a key role as regulator of physiological processes related to human reproduction. Melatonin is involved in the normal outcome of pregnancy, beginning with the oocyte quality, continuing with embryo implantation, and finishing with fetal development and parturition. Melatonin has been shown to act directly on several reproductive events, including folliculogenesis, oocyte maturation, and corpus luteum (CL) formation. The molecular mechanism of action has been investigated through several studies which provide solid evidence on the connections between maternal melatonin secretion and embryonic and fetal development. Melatonin administration, reducing oxidative stress and directly acting on its membrane receptors, melatonin thyroid hormone receptors (MT1 and MT2), displays effects on the earliest phases of pregnancy and during the whole gestational period. In addition, considering the reported positive effects on the outcomes of compromised pregnancies, melatonin supplementation should be considered as an important tool for supporting fetal development, opening new opportunities for the management of several reproductive and gestational pathologies.

Keywords: embryo implantation; fetal development; melatonin; oocyte quality; pregnancy.

Figure 1

Pre-implantation stage. Physiological secretion of melatonin allows it to interact with melatonin membrane receptors (MT1-MT2) in endometrial cells and the blastocyst. Melatonin signaling creates a positive feedback loop among p53, p38, and p21, activating lif transcription and inhibiting mucin 1 secretion. The result is a better interaction among the adhesion proteins present at the membrane level on endometrial cells and the blastocyst.

Figure 2

Melatonin local effects on implantation. Melatonin acts on different levels of implantation capacity. The cytoprotective capacity allows us to check ovarian aging by increasing sirtuins transcription (Sirt1/3/6) that protect the 3′ end of chromosomes (telomeres) reducing the cellular senescence. ROS reduction is led by melatonin’s direct action and biosynthesis of catalase and superoxide dismutase 1. Their transcription is powered through melatonin administration in ovarian cells and blastocysts. Moreover, the apoptosis regulation and a powered adhesion proteins expression by melatonin increase the rate of blastocyst implantation.