The association between the oocyte pool and aneuploidy: a comparative study of the reproductive potential of young and aged mice

Abstract

Purpose The present study examined the effect of aging on female reproductive potential. Methods Six-week-old and 9-month-old CD1 mice were referred to as the 'young' and 'aged' groups, respetively. Oocytes were collected after superovulation, and their viability were compared using parthenogenetic activation. The aneuploidy of the oocytes (MII) was assessed using chromosome spread, and the whole ovarian follicle number was counted using an unbiased stereological method. Serum hormone levels were measured using the radio-immunity method, and the expression of the Cohesin subunit genes in the oocytes (GV) were assessed using RT-PCR. Results The mean number of recovered (25.8 vs. 16.2; P<0.05) and live oocytes (24.0 vs. 11.73; P <0.01) per head in the young-mice group (6-week-old) was significantly higher than that of the aged group (9-month-old). The aneuploidy rate of the ovulated oocytes in the aged group was significantly higher than that of the young group (36.8 % vs. 10 %; P<0.01), and the rate of blastocyst formation in the young group (85.23 %) was significantly higher than that of the aged group (81.2 %; P <0.05). The number of primordial follicles (the oocyte pool) per ovary in the aged group was significantly decreased compared with the young group (330±33.51 vs. 2079.6±420.70; P<0.01), and the level of AMH in the aged group was significantly higher than that of the young group (4.66±0.11 ng/ml vs. 4.07±0.18 ng/ml; P<0.01). Conclusions We propose that maternal aging significantly reduces the oocyte pool, superovulation efficiency and developmental potential and increases the oocyte aneuploidy rate.

Effects of dietary quercetin on female fertility in mice: implication of transglutaminase 2

“…3 a ). Females in the B2 period may represent those at the onset of reproductive senescence as the number of litters born to them, normalised to the duration of breeding, was reduced by ~80% compared with young females in both control (grey bars) and quercetin-treated females (black bars; Fu et al 2013). These data indicate that quercetin does not alter the onset of reproductive senescence.…”

A putative role for anti-Müllerian hormone (AMH) in optimising ovarian reserve expenditure

“…For example, ageing mice maintain a similarly-sized large antral follicle pool to young mice but the older mice recruit from smaller primary follicle pools and have higher rates of aneuploidy (Fu et al 2014). Ovarian reserve, determined by AMH levels, is correlated with litter size in dogs (Hollinshead et al 2016), which could have large consequences for cumulative, lifetime reproductive fitness.…”

Elevated intracellular pH appears in aged oocytes and causes oocyte aneuploidy associated with the loss of cohesion in mice

“…3,6 Maternal age-related aneuploidy is a consequence of chromosome segregation errors during meiotic division. [7][8][9] In meiosis I, the crucial ploidy reduction step requires that sister kinetochores attach to microtubules emanating from the same spindle pole and that cohesin wrapped around chromosome arms dissolves. In meiosis II, chromosome segregation requires that sister kinetochores attach to opposite spindle poles and that centromeric cohesion dissolves.…”