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.

Melatonin for prevention of placental malperfusion and fetal compromise associated with intrauterine inflammation‐induced oxidative stress in a mouse model

“…Melatonin easily crosses the placenta and the blood‐brain barrier and is considered to be important for normal placental function as well as fetal growth and brain development . Furthermore, current studies demonstrate that melatonin supplementation is relatively safe for the mother and the fetus …”

“…Melatonin, a major secretory hormone of the pineal gland, has antioxidant and anti‐inflammatory effects. While melatonin is primarily produced in the pineal gland, the placenta acts as one of the major extrapineal sources of melatonin during pregnancy . Melatonin easily crosses the placenta and the blood‐brain barrier and is considered to be important for normal placental function as well as fetal growth and brain development .…”

“…While melatonin is primarily produced in the pineal gland, the placenta acts as one of the major extrapineal sources of melatonin during pregnancy. 13,14 Melatonin easily crosses the placenta and the blood-brain barrier and is considered to be important for normal placental function as well as fetal growth and brain development. 15,16 Furthermore, current studies demonstrate that melatonin supplementation is relatively safe for the mother and the fetus.…”

“…15,16 Furthermore, current studies demonstrate that melatonin supplementation is relatively safe for the mother and the fetus. 13,[17][18][19] As an antioxidant and anti-inflammatory agent, melatonin inhibits lipopolysaccharide (LPS)-induced release of reactive oxygen species (ROS) and inflammatory cytokines and chemokines. [20][21][22] Previous studies have shown that melatonin protects mice from LPS-induced fetal death, intrauterine fetal growth restriction, and preeclampsia through its antioxidant and antiinflammatory effects.…”

Expression of melatonin receptors and CD4 in the ovine thymus, lymph node, spleen and liver during early pregnancy

“…Free radical damage is commonplace during pregnancy, and it has negative effects on the mother, placenta and fetus. Because of its antioxidant ability, melatonin can protect the fetus, maternal tissues and placenta from oxidative damage, which is beneficial for normal reproductive physiology 25–27 . Melatonin treatment can increase pregnenolone synthesis in the ovary and endometrium, which promotes endometrial development and embryo implantation early in mouse pregnancy 28 .…”