Melatonin, Its Beneficial Effects on Embryogenesis from Mitigating Oxidative Stress to Regulating Gene Expression

Abstract

Embryogenesis is a complex multi-stage process regulated by various signaling molecules including pineal and extrapineal melatonin (MT). Extrapineal MT is found in the placenta and ovaries, where it carries out local hormonal regulation. MT is necessary for normal development of oocytes, fertilization and subsequent development of human, animal and avian embryos. This review discusses the role of MT as a regulator of preimplantation development of the embryo and its implantation into endometrial tissue, followed by histo-, morpho- and organogenesis. MT possesses pronounced antioxidant properties and helps to protect the embryo from oxidative stress by regulating the expression of the NFE2L2, SOD1, and GPX1 genes. MT activates the expression of the ErbB1, ErbB4, GJA1, POU5F1, and Nanog genes which are necessary for embryo implantation and blastocyst growth. MT induces the expression of vascular endothelial growth factor (VEGF) and its type 1 receptor (VEGF-R1) in the ovaries, activating angiogenesis. Given the increased difficulties in successful fertilization and embryogenesis with age, it is of note that MT slows down ovarian aging by increasing the transcription of sirtuins. MT administration to patients suffering from infertility demonstrates an increase in the effectiveness of in vitro fertilization. Thus, MT may be viewed as a key factor in embryogenesis regulation, including having utility in the management of infertility.

Prenatal Molecular Hydrogen Administration Ameliorates Several Findings in Nitrofen-Induced Congenital Diaphragmatic Hernia

“…H 2 has been reported to increase Kdr expression in rat lung, which is consistent with the present result [36]. Melatonin, an antioxidant, increases VEGFR-1 levels [37], which suggests that antioxidants improve VEGFR-1 expression.…”

The role of oxidative stress in ovarian aging: a review

“…Melatonin can also upregulate antioxidant enzyme expression by inducing demethylation of the promoter regions of SOD, GSH-Px4 and CAT, thereby enhancing the antioxidant capacity of cumulus cells [ 217 ]. Melatonin activates ErbB1 and ErbB4 gene expression to promote embryo implantation and blastocyst growth, and further protects embryos from OS [ 218 ].…”

Resveratrol and SIRT1: Antiaging Cornerstones for Oocytes?

“…Some molecules have the natural ability to activate SIRT1 [ 68 ]. The positive effects of melatonin on oocytes, which activate several antioxidant pathways, may be one solution to excessive aging [ 69 , 70 ]. Among the activated genes associated with reducing ROS (Sod1, Sod2, Nrf2), SIRT1 is also prominent [ 8 , 71 ].…”