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

Abstract

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.

摘要

众所周知, 线粒体在生殖能力的调节中起着关键作用。衰老会损害线粒体的功能, 最终会损害细胞的能量代谢。因此, 随着女性年龄的增长, 能量供应不足很可能会影响卵子的质量。颗粒细胞分析被认为是评估与卵母细胞能力有关因素的一种有价值的无创策略。因此, 我们进行了一项前瞻性队列研究, 以评估衰老对黄素化颗粒细胞(LGC)能量产生的影响。对照组包括13名年轻的卵子捐献者, 而研究组包括13名38岁以上接受体外受精的不孕女性。患可能影响线粒体功能的疾病的女性被排除在外。年轻捐献者和高龄不孕症患者LGC中ATP水平无明显差异(对照组为1.9±0.99皮摩尔, 对照组为2.1±0.59皮摩尔；p值 = .139)。同样, 我们系列中的ATP水平与卵母细胞数量或成熟度都没有相关性。尽管LGC的ATP水平相似, 但不能排除年龄对生物能量状态的影响。能量代谢非常复杂, ATP似乎不是最重要、最可靠的参数。

Keywords:

• ART
• ATP
• granulosa cells
• mitochondria
• senescence

Acknowledgements

The results of this study were presented in part at the 32nd National Congress of the Spanish Fertility Society held in Madrid, Spain, 16–18 May 2018.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by MSD (IISP 53719). Additionally, GNC received grants from the Capes Foundation, Brazil/PDSE/Process number 88881.132905/2016-01.