Description
Female fertility is one of the first physiological functions undergoing age-related decline. One of its causes is suboptimal oocyte quality of aged females. Oocytes are established during prenatal development as a finite pool. Therefore, they can be several decades old in females of long-lived species, increasing the likelihood of the accumulation of various aberrations such as weaker chromatid cohesion, altered epigenomic landscape, increased transposon expression and DNA damage. Moreover, whole ovaries from aged females are affected by chronic pro-inflammatory response. Ovulations share characteristics with inflammatory response, and detrimental effect of ovulations on chromosomal segregation was uncovered. It is therefore essential to understand the impact of repeated ovulations on the quality of remaining oocytes, and to what extent it contributes to the aging-associated quality decline.
In addition to short-lived mouse ovulating every 4-5 days unless pregnant, we study long-lived African mole-rats forming cooperatively breeding colonies where only one female breeds and ovulates, while the remaining females are non-ovulating non-breeders. We evaluated DNA damage, epigenetic marks and transposon expression, revealing that the oocytes of aged females with fewer ovulations have better quality and are more similar to young females’ oocytes than the oocytes of aged females with more ovulations in both mice and mole-rats, suggesting that repeated ovulations play an important role in oocyte quality decline. However, in mole-rats, oocytes accumulate substantially fewer aberrations compared to mouse. This has implications for humans, where the causes of female suboptimal fertility and/or likelihood of chromosomal aberrations in fetus could be assessed not only by maternal age, but also by the age of the start of menstrual cycling, and hormonal contraception use.
