Developmental Potential of Prepubertal Mouse Oocytes Is Compromised Due Mainly to Their Impaired Synthesis of Glutathione

Abstract

Although oocytes from prepubertal animals are found less competent than oocytes from adults, the underlying mechanisms are poorly understood. Using the mouse oocyte model, this paper has tested the hypothesis that the developmental potential of prepubertal oocytes is compromised due mainly to their impaired potential for glutathione synthesis. Oocytes from prepubertal and adult mice, primed with or without eCG, were matured in vitro and assessed for glutathione synthesis potential, oxidative stress, Ca2+ reserves, fertilization and in vitro development potential. In unprimed mice, abilities for glutathione synthesis, activation, male pronuclear formation, blastocyst formation, cortical granule migration and polyspermic block were all compromised significantly in prepubertal compared to adult oocytes. Cysteamine and cystine supplementation to maturation medium significantly promoted oocyte glutathione synthesis and blastocyst development but difference due to maternal age remained. Whereas reactive oxygen species (ROS) levels increased, Ca2+ storage decreased significantly in prepubertal oocytes. Levels of both catalytic and modifier subunits of the γ-glutamylcysteine ligase were significantly lower in prepubertal than in adult oocytes. Maternal eCG priming improved all the parameters and eliminated the age difference. Together, the results have confirmed our hypothesis by showing that prepubertal oocytes have a decreased ability to synthesize glutathione leading to an impaired potential to reduce ROS and to form male pronuclei and blastocysts. The resulting oxidative stress decreases the intracellular Ca2+ store resulting in impaired activation at fertilization, and damages the microfilament network, which affects cortical granule redistribution leading to polyspermy.

Effects of embryo-derived exosomes on the development of bovine cloned embryos

“…In this study, using bovine SCNT embryos as the model, we systematically assessed effects of culture medium renewal on blastocyst formation and quality ( in vitro development) and following growth to term ( in vivo development). Our results (Table 3) showed that compared with routine renewal treatment, continuous nonrenewal culture system exhibited a significant improvement in blastocyst formation, total cell number, ratio of ICM/TE (Fig 5), pregnancy and calving (Table 4), as well as a remarkable decrease in cellular stress (reduced expression of Bip , an endoplasmic reticulum stress marker [33], Fig 6) and apoptosis (increased Bcl-2— an anti-apoptosis marker [34] and reduced Bax— a pro-apoptosis marker [35], Fig 6; and less TUNEL signal, Fig 4). Notably, coupling of endoplasmic reticulum stress and apoptosis detected in our study is consistent with previous studies [36, 37].…”

Maternal age effect on mouse oocytes: new biological insight from proteomic analysis

“…The abundance of GSTO1 increased in both the first and second age transition. Although there is no study of GSTO1 in mammalian oocytes, impaired synthesis of glutathione is indicted as the main cause for compromised developmental potential of pubertal mouse oocytes in mice (Jiao et al 2013); hence, the increased abundance of GSTO1 in old oocytes may facilitate development. Abundance of the cell death inducer BAX was high in pubertal oocytes and decreased in the first age transition.…”

Oxidative Stress Induces Mouse Follicular Granulosa Cells Apoptosis via JNK/FoxO1 Pathway

“…Research indicated that granulosa cells apoptosis can cause the follicular atresia [2]. Moreover, several studies showed that follicular granulosa cells have a crucial role in oocyte potency in sheep [3], mouse [4], porcine [5], goat [6]and rat [7]. Therefore, follicular granulosa cells play an important function during female reproduction.…”