Melatonin promotes the in vitro development of pronuclear embryos and increases the efficiency of blastocyst implantation in murine

Abstract

When a defect occurs in the in vitro development of a pronuclear embryo, the interruption of the subsequent implantation limits the success of assisted conception. This common problem remains to be solved. In this study, we observed that melatonin at its physiological concentration (10(-7) m) significantly promoted the in vitro development of murine pronuclear embryos. This was indicated by the increased blastocyst rate, hatching blastocyst rate, and blastocyst cell number with melatonin treatment. In addition, when these blastocysts were implanted into female recipient mice, the pregnancy rates (95.0% versus control 67.8%), litter sizes (4.1 pups/litter versus control 2.7 pups/litter), and postnatal survival rates of offspring (96.84% versus control 81.24%) were significantly improved compared with their non-melatonin-treated counterparts. Mechanistic studies revealed that melatonin treatment upregulates gene expression of the antioxidant enzyme, superoxide dismutase (SOD), and the anti-apoptotic factor bcl-2 while downregulating the expression of pro-apoptotic genes p53 and caspase-3. Due to these changes, melatonin treatment reduces ROS production and cellular apoptosis during in vitro embryo development and improves the quality of blastocysts. The implantation of blastocysts with higher quality leads to more healthy offspring and increased pup survival.

Antioxidative Capacity Of Melatonin In Follicular Fluid Of Aged IVF Patients: Beneficial Effects On Oocytes And Embryo

“…These data were supported by recent study that demonstrates like supplement of metformin or D-chio-inositol (DCI) decrease the oxidative damage on follicular fluid proteins in women with polycystic ovary syndrome (PCOS) [33] . In conclusion it suggest an important scavenger role of melatonin which results in better oocytes and embryo quality in aged women, supported by previous study on murine [34] . Our suggestion is to give a melatonin supplementation to aged patients under went IVF.…”

Essential actions of melatonin in protecting the ovary from oxidative damage

“…Melatonin enhances mRNA levels for both CuZnSOD and MnSOD in rat tissues [67], GSH synthesis in human endothelial cells [43], and prevents the induction of the intrinsic mitochondrial pathway of apoptosis by inducing Bcl-2 expression and reducing caspase 3 activity; these actions protect cells against oxidative stress and regulate cell proliferation in murine [68]. Exogenous administration of melatonin significantly reduces intrafollicular oxidative damage and oxidative mutilation of essential molecules, which enhances subsequent fertilization and pregnancy rates in human [21,42].…”

Melatonin promotes Bax sequestration to mitochondria reducing cell susceptibility to apoptosis via the lipoxygenase metabolite 5-hydroxyeicosatetraenoic acid

“…The anti-apoptotic effect of melatonin is generally attributed to its radical scavenging ability, since apoptosis is partially dependent on oxidation (Espino et al, 2010;Kim et al, 2009;Wang et al, 2013). This belief is reinforced by the notion that doses of melatonin required to inhibit apoptosis coincide with those required for radical scavenging (Kim et al, 2009).…”