Rapamycin preserves the follicle pool reserve and prolongs the ovarian lifespan of female rats via modulating mTOR activation and sirtuin expression

Geroconversion: irreversible step to cellular senescence

“…For example, geroconversion of stem cells may initially increase their proliferation followed by delayed arrest (stem cell exhaustion). 15,[92][93][94][95][96][97] Similar geroconversion exhausts oocytes, 98,99 leading to menopause. Cell cycle arrest per se cannot be linked to age-related diseases.…”

PI3K/PTEN/Akt and TSC/mTOR signaling pathways, ovarian dysfunction, and infertility: an update

“…Rapamycin treatment prevented global follicular activation and preserved the ovarian reserve. Zhang et al (2013b) studied the effects of rapamycin on PF development in rats. The treated group demonstrated decreased mTOR but increased sirtuin signaling, indicating that rapamycin might inhibit the transition from primordial to developing follicles and preserve the follicle pool reserve via modulation of the mTOR and sirtuin signaling (Table 1).…”

“…Results from a recent study have indicated that 3,5,3 0 -triiodothyronine (T 3 ) increases FSHinduced preantral follicle growth in vitro through inhibition of cell apoptosis and promotion of cell proliferation. The survival effects of hormones were mediated through activation of the Src/PI3K/Akt pathway (Zhang et al 2013b). FSH and LH exert their effect by binding to specific GPCRs, which in turn cause an increase in cAMP production and activation of the protein kinase A (PKA) pathway (Ryan et al 2008).…”

Follicle aging: a question of stress?

“…The expression of sirtuins has been observed in mammalian ovaries, granulosa cells (GCs), oocytes and embryos (29). In rat ovaries caloric restriction and rapamycin seem to inhibit the transition from primordial to developing follicles and preserve the follicle pool reserve through a fine-tuning of SIRT1 signalling (30,31). By contrast in ovaries from high fat diet, down-regulation of SIRT1 signalling was associated with accelerated ovarian development and follicle loss (32).…”

“…A recent paper has provided evidence for the effectiveness of resveratrol in preventing ovarian aging in mice (45). SIRT1 signalling has also been involved in the beneficial effects on fertility attained by dietary supplementation of compounds other than STACs (31). Accordingly diet with deleterious effects on fertility results in Sirt1 suppression.…”