Pyruvate prevents aging of mouse oocytes

Abstract

Inhibiting oocyte aging is important not only for healthy reproduction but also for the success of assisted reproduction techniques. Although our previous studies showed that cumulus cells accelerated aging of mouse oocytes, the underlying mechanism is unknown. The objective of this paper was to study the effects of pyruvate and cumulus cells on mouse oocyte aging. Freshly ovulated mouse cumulus-oocyte complexes (COCs) or cumulus-denuded oocytes (DOs) were cultured in Chatot-Ziomek-Bavister (CZB) medium or COC-conditioned CZB medium supplemented with different concentrations of pyruvate before being examined for aging signs and developmental potential. Pyruvate supplementation to CZB medium decreased rates of ethanol-induced activation in both COCs and DOs by maintaining their maturation-promoting factor activities, but more pyruvate was needed for COCs than for DOs. Addition of pyruvate to the COC-conditioned CZB also alleviated aging of DOs. Observations on cortical granules, level of BCL2 proteins, histone acetylation, intracellular concentration of glutathione, and embryo development all confirmed that pyruvate supplementation inhibited aging of mouse oocytes. It is concluded that the aging of mouse oocytes, facilitated by culture in COCs, can be partially prevented by the addition of pyruvate to the culture medium.

Epigenetic changes associated with oocyte aging

“…When the time of aging progressed to 24 h of hCG injection, AcH3K14 was also detected and displayed an increase of fluorescence signals in the oocytes. Our observation was further confirmed by Liu et al [51] who found that AcH3K14 and AcH4K12 showed an increase in acetylation in mouse oocytes during postovulatory aging. Although unlike mouse oocytes, AcH4K12 was acetylated in mature porcine oocytes, its acetylation level increased during postovulatory aging [52].…”

Oxidative stress and ageing of the post-ovulatory oocyte

“…A decrease in fertilization rate has been associated with aged oocytes in many species including the humans (Lash & Whittaker 1974), mice (Marston & Chang 1964, Liu et al 2009b, cows (Chian et al 1992) and pigs (Kikuchi et al 2000). This phenomenon can be attributed to multiple biochemical and functional alterations to the oocyte that accumulate with post-ovulatory age.…”

“…Following these observations, it has been hypothesized that cumulus cells secrete soluble/ paracrine factor(s) that promote post-ovulatory ageing, potentially an event that coincides with the entry of the cumulus cells into apoptosis . Additionally, the accelerated depletion of the oocyte metabolite pyruvate from culture medium by cumulus cells (Downs et al 2002) appears to directly affect oocyte metabolism and hence post-ovulatory ageing, potentially by causing downstream inhibition of protein synthesis within the oocyte and upsetting redox equilibrium (Liu et al 2009b). …”

“…Specifically, increasing the concentration of pyruvate within culture media has been shown to delay post-ovulatory ageing by maintaining cortical granule integrity, decreasing susceptibility to activating stimuli, preventing an ageassociated decline in levels of MPF and glutathione, improving blastocyst formation rates following fertilization and delaying the onset of apoptosis (Liu et al 2009b, Li et al 2012. As the oocyte and early embryo preferentially utilize pyruvate over glucose to drive metabolism (Leese & Barton 1984), it has been proposed that pyruvate supplementation delays oocyte ageing by fuelling prolonged ATP production within oocytes and also by maintaining intracellular redox potential (Liu et al 2009b. Increased pyruvate concentration is particularly effective in preventing accelerated in vitro ageing of the cumulus-enclosed MII oocyte, a result likely attributed to the more rapid depletion of pyruvate from culture media in the presence of cumulus cells (Downs et al 2002).…”

An insufficient increase of cytosolic free calcium level results postovulatory aging-induced abortive spontaneous egg activation in rat

“…Postovulatory aging-induced abortive SEA deteriorates the egg quality and limits assisted reproductive technologies (ART) such as in vitro fertilization (IVF), intra-cytoplasmic sperm injection (ICSI) and somatic cell nuclear transfer (SCNT) during animal cloning [14,[17][18][19]. Several drugs such as proteasome inhibitor, MG-135 [20,21], melatonin [22], verapamil [16] and pyruvate [23] have been used to prevent postovulatory aging-induced abortive SEA in vitro [16,24].…”