Abstract
Over the past four decades, due to cultural and social changes, women in the developed world have significantly delayed childbirth. This trend is even worse for patients who attend infertility clinics. It is well-known that live birth rates in women older than 35 are significantly lower than in those younger, both naturally and with assisted reproduction. Fertility decline is, in part, due to an increase in oocyte aneuploidy that leads to a reduced embryo quality, as well as an increased incidence of miscarriages and birth defects. Here we show that aging-associated malfunction is not restricted to the oocyte, as cumulus granulosa cells also display a series of defects linked to mitochondrial activity. In, both, human and mouse model, a decline in cumulus cell function due to increased maternal age is accompanied by a decreased expression of enzymes responsible for Coenzyme Q (CoQ) production, particularly Pdss2 and CoQ6. In an aged mouse model supplementation with Coenzyme Q10—a potent stimulator of mitochondrial function—restored cumulus cell number, stimulated glucose uptake, and increased progesterone production. CoQ10 supplementation might, thus, improve oocyte and cumulus cells quantity and quality, by improving the mitochondrial metabolism in females of advanced maternal age.
Highlights
Due to various cultural and social shifts occurring in the past 50 years, women in most western countries significantly postpone the decision to have a child [1]
We examined whether aging is associated with a decline in the expression of genes involved in the Coenzyme Q (CoQ) production and the physiological function of cumulus cells
We examined the expression of genes involved in the CoQ10 synthesis pathway in the murine cumulus cells
Summary
Due to various cultural and social shifts occurring in the past 50 years, women in most western countries significantly postpone the decision to have a child [1] This is reflected in a 36% increase in the proportion of first births in women in their mid- to late-30s, with an even more dramatic increase for women over 40 [2]. We have previously proposed that decline in mitochondrial function could be one of the driving factors behind the accelerated aging of oocyte [4]. We examined whether aging is associated with a decline in the expression of genes involved in the CoQ production and the physiological function of cumulus cells. Our results point to the overlapping age-associated decrease in the expression of both Pdss and CoQ6, in both cell types
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