Reproductive senescence and energetic metabolism of human luteinized granulosa cells: is it all about ATP? A prospective cohort and critical view.

Mitochondria are known to play a key role in the regulation of reproductive capacity. Senescence is known to impair mitochondrial function and, ultimately, cellular energetic metabolism. Therefore, as women age, a deficient energy supply is likely to affect oocyte quality. The analysis of granulosa cells is considered a valuable noninvasive strategy to assess factors implicated in oocyte competence. Thus, we conducted an observational prospective cohort to evaluate the impact of aging on energy production by luteinized granulosa cells (LGCs). The control group comprised 13 young oocyte donors, whereas the comparison group included 13 infertile women over 38 years of age undergoing in vitro fertilization. Women with diseases that could potentially impact mitochondrial function were excluded. No differences were detected in the ATP levels in LGCs from young donors and infertile patients of advanced reproductive age (1.9 ± 0.99 picomoles in the control group vs. 2.1 ± 0.59 picomoles; p-value = .139). Likewise, the ATP levels in our series did not correlate with either oocyte number or maturity. Despite the similar ATP levels in LGCs, an age effect on the bioenergetic status cannot be excluded. Energy metabolism is very complex, and ATP does not seem to be the most important and reliable parameter.