Cumulus cells accelerate aging of mouse oocytes by secreting a soluble factor(s)

Abstract

Control of oocyte aging in vitro is important for both human-assisted reproduction and animal embryo technologies because fertilization or artificial activation of aged oocytes results in abnormal development. Interactions between somatic and germ cells are also an important issue in current biological research. The role of cumulus cells (CCs) in maturation, ovulation, and fertilization of oocytes has been extensively studied, yet little is known about their role in oocyte aging. Although our previous study has shown that CCs accelerate the aging progression of mouse oocytes, the mechanism by which CCs accelerate oocyte aging is unknown. In this study, cumulus-denuded mouse oocytes (DOs) were co-cultured with cumulus-oocyte complexes (COCs) or CC monolayer or cultured in medium conditioned with these cells and changes in the susceptibility to activating stimuli and in MPF activity of oocytes were evaluated after different aging treatments. The results showed that culture with or in medium conditioned with COCs or CC monolayer promoted activation of DOs, indicating that a soluble factor is responsible for the aging-promoting effect. The in vivo and in vitro-matured DOs did not differ in responsiveness to the aging-promoting factor (APF). Heat shock did not accelerate oocyte aging unless in the presence of CCs. The production of APF was not affected by the age or maturation system of COCs, but increased with their density and duration of culture. The results strongly suggest that CCs accelerated oocyte aging by secreting a soluble APF into the medium. Further analysis showed that the APF was heat labile but stable to freezing, it had a threshold effective concentration and can be depleted by DOs.

Pyruvate prevents aging of mouse oocytes

“…During aging of cumulus-denuded oocytes (DOs), however, activation rates remained low and the MPF activity decreased much more slowly compared with that of oocytes aged with cumulus cells. Our second study showed that both co-culture with COCs or monolayer of cumulus cells and culture in medium conditioned with these cells promoted activation of DOs (Qiao et al 2007). The results strongly suggest that cumulus cells accelerate aging of mouse oocytes, most probably by secreting a soluble factor(s).…”

“…The role of the surrounding cumulus cells in maturation, ovulation, and fertilization of oocytes has been extensively studied (Eppig 1982, 1991, Buccione et al 1990, Tanghe et al 2002); yet little is known about their role in oocyte aging. Moreover, although the cumulus cells have been found to play an important role in maturation, ovulation, and fertilization of oocytes, their mechanisms of action are poorly understood (Tanghe et al 2002, Ge et al 2007. In recent years, two studies were conducted in this laboratory to investigate the role and mechanisms of action of cumulus cells in mouse oocyte aging.…”

Oxidative stress and ageing of the post-ovulatory oocyte

“…In vivo aged oocytes and in vitro aged oocytes enclosed within the cumulus cell complex experience increased rates of spontaneous activation and fragmentation (Miao et al 2005, accelerated decline of MPF/MAPK (Miao et al 2005) and decreased levels of blastocyst formation ) when compared with denuded oocytes aged in vitro. Qiao et al (2007) reported that the addition of cumulus cells to culture medium containing denuded oocytes caused an acceleration of post-ovulatory ageing on par with that of oocytes enclosed in a cumulus-oocyte complex, while other research groups have demonstrated that blocking gap junctions within the cumulus-oocyte complex does not prevent accelerated ageing . 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 .…”

Mitochondrial functions on oocytes and preimplantation embryos

“…As we know, during meiotic progression, oocyte maturation also couples with cumulus expansion or apoptosis and the number of cumulus cells attached to matured oocytes decreases with age (Qiao et al, 2008). Torner et al(2004) found that mitochondrial redistribution and their oxidative activity are essential to the degree of cumulus cell apoptosis during oocyte maturation.…”