Melatonin promotes human oocyte maturation and early embryo development by enhancing clathrin‐mediated endocytosis

Abstract

Embryo development potential and reproductive clinical outcomes are all deeply rooted in oocyte maturation. Melatonin has been reported to promote oocyte maturation as an antioxidant in nonprimate species. Its antioxidative functions also help reduce plasma membrane rigidity, which facilitates clathrin‐mediated endocytosis (CME). Whether melatonin has effects on human oocyte maturation by regulating CME is worthy of exploration. In this study, we found that the optimal melatonin concentration for human oocyte maturation was 10−11 M, and the maturation rate of this group was 71.9% (P = .03). The metaphase II (MII) stage oocytes obtained by in vitro maturation with 10−11 M melatonin had a significantly higher fertilization rate (81.4% vs 61.4%, respectively, P = .017) and blastocyst rate (32.2% vs 15.8%, respectively, P = .039) compared to controls. During maturation, antioxidative melatonin greatly enhanced CME and decreased intra‐oocyte cAMP level. The former was evidenced by the increasing numbers of coated pits and vesicles, and the upregulated expression of two major CME markers—clathrin and adaptor protein‐2 (AP2). CME inhibitor dynasore increased intra‐oocyte cAMP level and blocked oocyte maturation, and melatonin could partly rescue oocyte maturation and significantly elevate the expression of clathrin and AP2 in the presence of dynasore. Therefore, we conclude that melatonin could promote human oocyte maturation and early embryo development through enhancing CME.

Quercetin promotes in vitro maturation of oocytes from humans and aged mice

“…It is thought that many effects on embryonic development and clinical outcomes are deeply rooted in the oocyte maturation process 36 . However, because of suboptimal culturing conditions, IVM oocytes have been reported to exhibit embryonic developmental arrest at various stages 37 .…”

Melatonin promotes the development of immature oocytes from the COH cycle into healthy offspring by protecting mitochondrial function

“…Melatonin and its metabolites are potent free radical scavengers and antioxidants in many organisms . It has been reported that MT can improve oocyte maturation in vitro and promote early embryo development in an animal model and even in humans; however, there is insufficient information on whether MT improves the developmental potential of immature human oocytes collected from the COH cycle and on the mechanisms of the effect.…”

“…Initially, MT was identified as a hormone primarily involved in the regulation of circadian rhythms of various physiological and neuroendocrine functions. However, MT has been recently shown to have multiple functions, especially in the reproductive system, by acting as a powerful free radical scavenger to protect the cells from oxidative stress damage, delay ovarian aging, regulate the production of progesterone, predict ovarian reserve, and in vitro fertilization (IVF) outcomes, as well as promote embryonic development …”

“…In the animal studies, attempts to optimize the IVM culture by supplementing the IVM media with MT have produced relatively desirable results . However, only a few similar studies have been performed in humans …”

Melatonin improves the first cleavage of parthenogenetic embryos from vitrified–warmed mouse oocytes potentially by promoting cell cycle progression

“…During in vitro culture, melatonin (MT) has been reported to promote development of both fresh [38][39][40][41][42][43] and/or vitrified oocytes/embryos [10,42,[44][45][46], mainly by one or more events such as modulating the oxidative stress, improving mitochondrial function, regulating spindle assembly, chromosome arrangement and expression of key genes, and inhibiting the apoptosis. Previously we have also reported that MT supplementation during the whole length of experiment (warming, recovery, parthenogenetic activation, and embryo culture steps) might promote G1-to-S progression via regulation of ROS, GSH and expression of cell cycle-related genes, potentially increasing the parthenogenetic development ability of vitrified-warmed mouse oocytes [10,36].…”