Beneficial effects of melatonin on bovine oocytes maturation: a mechanistic approach

Abstract

This study was performed to investigate the effect of melatonin on bovine oocyte maturation and subsequent embryonic development in vitro. The endogenous melatonin concentration in bovine follicular fluid is approximately 10(-11) M. To examine the potential beneficial effects of melatonin on bovine oocyte maturation in vitro, germinal vesicle (GV) oocytes were incubated with different concentrations of melatonin (10(-11), 10(-9), 10(-7), 10(-5), 10(-3) M). Melatonin supplementation at suitable concentrations significantly promoted oocyte maturation. The development of embryos and the mean cell number/blastocyst produced after in vitro fertilization were remarkably improved. The most effective melatonin concentrations obtained from the studies ranged from 10(-9) to 10(-7) M. The expression of melatonin receptor MT1 and MT2 genes was identified in cumulus cells, granulosa cells, and oocytes using reverse transcription PCR, immunofluorescence, and Western blot. The mechanistic studies show that the beneficial effects of melatonin on bovine oocyte maturation are mediated via melatonin membrane receptors as the melatonin receptor agonist (IIK7) promotes this effect while the melatonin receptor antagonist (luzindole) blocks this action. Mechanistic explorations revealed that melatonin supplementation during bovine oocyte maturation significantly up-regulated the expressions of oocyte maturation-associated genes (GDF9, MARF1, and DNMT1a) and cumulus cells expansion-related gene (PTX3, HAS1/2) and that LHR1/2, EGFR are involved in signal transduction and epigenetic reprogramming. The results obtained from the studies provide new information regarding the mechanisms by which melatonin promotes bovine oocyte maturation in vitro and provide an important reference for in vitro embryo production of bovine and the human-assisted reproductive technology.

Melatonin: A Mitochondrial Targeting Molecule Involving Mitochondrial Protection and Dynamics

“…Martin et al [25] subsequently observed that melatonin prevented the inhibition of mitochondrial complexes I and IV induced by ruthenium red and significantly reduced mitochondrial oxidative stress caused by t -butyl hydroperoxide; however, comparable doses of vitamins C and E lacked these protective effects [111]. The differences among melatonin and vitamin C and vitamin E on the relative protection of mitochondria may be explained by the observations that melatonin accumulates in mitochondria perhaps via the active transport by PEPT1/2 (unpublished observations Ma et al), but this is not the case with vitamin C and E. Many studies have confirmed the protective effects of melatonin against mitochondrial injury caused by different insults including ischemia/reperfusion [129,130], sepsis [131,132,133], in vitro fertilization (IVF) [134,135,136,137], 1-methyl-4-phenylpyridinium ion (MPP + ) [138], β-amyloid peptide (Aβ 25–35) [139,140], rotenone [141], 4-hydroxynonenal [142], arsenite [143], and lipopolysaccharide [144]. In addition to these mitochondrial injuries induced by exogenous interventions, melatonin also exhibits significant beneficial effects on several neurodegenerative diseases related to mitochondrial dysfunctions per se.…”

Beneficial Effects of Melatonin on the In Vitro Maturation of Sheep Oocytes and Its Relation to Melatonin Receptors

“…To solve this problem, many efforts have been made. Recently, the focus has been on melatonin, which is a potent antioxidant and free radical scavenger [2,3] due to its beneficial effects on oocytes maturation and embryo development [4,5,6,7,8,9,10,11,12,13,14]. Melatonin is well known for its physiological functions in seasonal reproduction, energy metabolism, and thermo-regulation in mammals [15].…”

Melatonin regulates antioxidative mechanisms in microalgaeChlamydomonas reinhardtii(Volvocales, Chlorophyceae)

“…In mammals, it is involved in processes of sleep, metabolic homeostasis, regulation of immune and reproduction systems and antioncogenic and antioxidative activity (Tan et al 2002;Rahman et al 2005;Garcia-Santos et al 2006;Yang et al 2007;Reiter et al 2014;Tian et al 2014). MLT is also found in eukaryotic unicellular organisms, plants, algae and prokaryotes (Reiter et al 2001;Köhidai et al 2002;Hardeland & Poeggeler 2003;Hardeland et al 2006;Iriti et al 2006;Okazaki et al 2009;Paredes et al 2009;Posmyk & Janas 2009).…”