Antioxidant supplementation overcomes the deleterious effects of maternal restraint stress-induced oxidative stress on mouse oocytes

Abstract

In this study, using a mouse model, we tested the hypothesis that restraint stress would impair the developmental potential of oocytes by causing oxidative stress and that antioxidant supplementation could overcome the adverse effect of stress-induced oxidative stress. Female mice were subjected to restraint stress for 24 h starting 24 h after equine chorionic gonadotropin injection. At the end of stress exposure, mice were either killed to recover oocytes for in vitro maturation (IVM) or injected with human chorionic gonadotropin and caged with male mice to observe in vivo development. The effect of antioxidants was tested in vitro by adding them to IVM medium or in vivo by maternal injection immediately before restraint stress exposure. Assays carried out to determine total oxidant and antioxidant status, oxidative stress index, and reactive oxygen species (ROS) and glutathione levels indicated that restraint stress increased oxidative stress in mouse serum, ovaries, and oocytes. Whereas the percentage of blastocysts and number of cells per blastocyst decreased significantly in oocytes from restraint-stressed mice, addition of antioxidants to IVM medium significantly improved their blastocyst development. Supplementation of cystine and cysteamine to IVM medium reduced ROS levels and aneuploidy while increasing glutathione synthesis and improving pre-and postimplantation development of oocytes from restraint-stressed mice. Furthermore, injection of the antioxidant epigallocatechin gallate into restraint-stressed mice significantly improved the blastocyst formation and postimplantation development of their oocytes. In conclusion, restraint stress at the oocyte prematuration stage impaired the developmental potential of oocytes by increasing oxidative stress and addition of antioxidants to IVM medium or maternal antioxidant injection overcame the detrimental effect of stress-induced oxidative stress. The data reported herein are helpful when making attempts to increase the chances of a successful outcome in human IVF, because restraint was applied at a stage similar to the FSH stimulation period in a human IVF program.

The lipid peroxidation product 4-hydroxynonenal contributes to oxidative stress-mediated deterioration of the ageing oocyte

“…Indeed, administration of melatonin during human ovarian stimulation in preparation for IVF reduced OS parameters and improved blastocyst quality and development 94 . Additionally, media supplementation with the antioxidants cystine and cysteamine during IVM resulted in decreased aneuploidy and improved embryo development after maternal restraint stress-induced OS 95 and maternal ageing 96 . In the context of this study, our data suggest that antioxidant supplementation may be able to prevent the generation of aldehydes such as 4-HNE and/or restrict their capacity to damage key meiotic proteins, including those of the tubulin family.…”

The Role of Antioxidant Enzymes in the Ovaries

“…Both enzymatic and nonenzymatic antioxidants can be useful for overcoming OS caused by ROS [13]. Antioxidant supplementation has been confirmed to have positive effects on mouse oocyte quality by reducing the harmful effects of OS [168]. Melatonin has frequently been investigated in recent years.…”

Endoplasmic Reticulum Stress Signaling in Mammalian Oocytes and Embryos: Life in Balance

“…These conditions can contribute to diabetes, growth abnormalities, and other long-term effects in progeny (Wyman et al ., 2008). Responses to other maternal stressors that may compromise oocyte quality and early embryogenesis can be accompanied by oxidative stress and increase in ROS production (Koyama et al, 2012; Lian et al, 2013; Ozawa et al, 2002). Embryo glutathione levels change during development and are altered in vitro (Gardiner and Reed, 1994).…”

“…Additionally, reduced glucose availability in vitro has long been recognized as beneficial to embryos (Chatot et al, 1989; Leese, 2012), although glucose starvation can actually increase ROS production and is not beneficial (Jansen et al, 2009). Other maternal stressors that may compromise oocyte quality and early embryogenesis can be redressed by antioxidant treatments (Lian et al ., 2013). Growth factors may also improve development after oxidative stress (Kurzawa et al, 2002).…”