Melatonin protects oocytes from MEHP exposure-induced meiosis defects in porcine†

Abstract

In 2011, DEHP (plasticizer) was reported to illegally be added in food and beverage products in Taiwan, which caused great concerns about food safety worldwide. DHEP has multiple toxic effects to human and animals such as endocrine disruption, cardiotoxicity, reproductive function, and development defects. However, the toxic effects of DEHP on mammalian oocyte quality are still unclear. Since MEHP is the active metabolite of DEHP in vivo, in this study we used porcine oocyte as model to explore the effects of MEHP on oocyte maturation and we also studied the effects of melatonin administration on MEHP exposure-induced meiosis defects. Our results showed that exposure to MEHP significantly decreased the polar body extrusion rate in porcine oocytes. Further study showed that cell cycle progression, meiotic spindle organization, and actin assembly were all disturbed after MEHP exposure. Moreover, the DNA and histone methylation levels were also affected, showing with altered 5mC and H3K4me2 levels. These results indicated that MEHP affected porcine oocyte maturation, while MEHP exposure-induced meiotic defects were all remarkably ameliorated by the administration of melatonin in porcine oocytes. We further tried to explore the causes of MEHP toxicity on oocytes, and we found that MEHP exposure resulted in significant elevations of oxidative stress and induced early apoptosis as well as elevated autophagy, while melatonin administration could reduce these. Taken together, our results indicated that MEHP exposure induced deterioration of oocyte quality, whereas melatonin supplement showed amelioration on oocyte maturation through its rescue effects on oocyte oxidative stress-mediated apoptosis and autophagy.

Melatonin enhances mitochondrial biogenesis and protects against rotenone‐induced mitochondrial deficiency in early porcine embryos

“…Thus, even a low concentration of melatonin can trigger a melatonin receptor‐dependent physiological response . Our study also revealed that melatonin concentration must approximately be 500 nmol/L to improve porcine embryo development, and previous studies have indicated that high concentrations of melatonin are also needed for porcine oocytes . Altogether, these results indicate that high concentrations of melatonin may mediate protective effects in porcine oocytes or early embryos.…”

“…Further, melatonin reportedly promotes oocyte maturation, fertilization, and early embryo development in various mammalian species . Moreover, it has been shown to protect against toxin‐induced oocyte quality impairment during maturation, mainly via its free radical scavenging and anti‐apoptosis activities . However, its beneficial effects on toxin‐exposed early embryos during in vitro culture and the possible mechanisms underlying such effects have not been investigated.…”

Effect of Melatonin on the In Vitro Maturation of Porcine Oocytes, Development of Parthenogenetically Activated Embryos, and Expression of Genes Related to the Oocyte Developmental Capability

“…Melatonin has a wide range of roles in physio-pathological functions, and is partly mediated by melatonin receptors in animals [23]. Melatonin treatment improves cumulus oophorus expansion of porcine COCs during IVM [24], and also increases the first polar body extrusion rate of the oocytes disrupted by heat stress and mono-(2-ethylhexyl) phthalate exposed in the porcine [7,25]. Melatonin participates in modulating functions of granulosa cell through melatonin receptor 2 (MT2), and also promotes cumulus expansion of COCs via MT2 in pigs [26].…”

Melatonin supplementation during in vitro maturation of oocyte enhances subsequent development of bovine cloned embryos

“…In this study, we found that melatonin suppressed early apoptosis in IVM bovine oocytes. Several recent studies have shown that melatonin decreased ROS production and early apoptosis in mouse and porcine oocytes exposed to mycotoxins and toxicants and promoted oocyte maturation (Lan et al, ; Miao et al, ; M. Zhang et al, ; Y. Zhang et al, ). However, the underlying mechanism remains unclear.…”