Department of Gynecology, Federal University of São Paulo, São Paulo, Brazil; Department of Gynecology and Obstetrics, Rey Juan Carlos University, Alcorcón Madrid, Spain; IVI-Madrid, Aravaca Madrid 28023, Spain.
Department of Gynecology and Obstetrics, Rey Juan Carlos University, Alcorcón Madrid, Spain; IVI-Madrid, Aravaca Madrid 28023, Spain.
Reprod Biomed Online. 2021 Nov;43(5):779-787. doi: 10.1016/j.rbmo.2021.08.006. Epub 2021 Aug 11.
Female age is the single greatest factor influencing reproductive performance and granulosa cells are considered as potential biomarkers of oocyte quality. Is there an age effect on the energy metabolism of human mural granulosa cells?
Observational prospective cohort and experimental study including 127 women who had undergone IVF cycles. Women were allocated to two groups: a group of infertile patients aged over 38 years and a control group comprising oocyte donors aged less than 35 years. Individuals with pathologies that could impair fertility were excluded from both groups. Following oocyte retrieval, cumulus and granulosa cells were isolated and their bioenergetic properties (oxidative phosphorylation parameters, rate of aerobic glycolysis and adenine nucleotide concentrations) were analysed and compared.
Human mural luteinized granulosa and cumulus cells present high rates of aerobic glycolysis that cannot be increased further when mitochondrial ATP synthesis is inhibited. Addition of follicular fluid to the experimental media is necessary to reach the full respiratory capacity of the cells. Granulosa cells from aged women present lower mitochondrial respiration (12.8 ± 1.6 versus 11.2 ± 1.6 pmol O/min/mg; P = 0.046), although mitochondrial mass is not decreased, and lower aerobic glycolysis, than those from young donors (12.9 ± 1.3 versus 10.9 ± 0.5 mpH/min/mg; P = 0.009). The concurrent decrease in the two energy supply pathways leads to a decrease in the cellular energy charge (0.87 ± 0.01 versus 0.83 ± 0.02; P < 0.001).
Human mural luteinized granulosa cells exhibit a reduction in their energy metabolism as women age that is likely to influence female reproductive potential.
女性年龄是影响生殖性能的最大单一因素，而颗粒细胞被认为是卵母细胞质量的潜在生物标志物。人类壁层颗粒细胞的能量代谢是否存在年龄影响？
包括 127 名接受 IVF 周期的女性在内的观察性前瞻性队列和实验研究。将女性分为两组：一组为年龄超过 38 岁的不孕患者，另一组为年龄小于 35 岁的卵母细胞供体对照组。两组均排除可能影响生育能力的病理情况。取卵后，分离出卵丘-颗粒细胞，分析比较其生物能量特性（氧化磷酸化参数、有氧糖酵解率和腺嘌呤核苷酸浓度）。
人类壁层黄体化颗粒细胞和卵丘细胞呈现出高的有氧糖酵解率，当线粒体 ATP 合成被抑制时，无法进一步增加。向实验培养基中添加卵泡液是达到细胞完全呼吸能力所必需的。与年轻供体相比，老年妇女的颗粒细胞表现出较低的线粒体呼吸（12.8 ± 1.6 对 11.2 ± 1.6 pmol O/min/mg；P = 0.046），尽管线粒体质量没有减少，并且有氧糖酵解也较低（12.9 ± 1.3 对 10.9 ± 0.5 mpH/min/mg；P = 0.009）。两种能量供应途径的同时减少导致细胞能量电荷减少（0.87 ± 0.01 对 0.83 ± 0.02；P < 0.001）。
随着女性年龄的增长，人类壁层黄体化颗粒细胞的能量代谢减少，这可能会影响女性的生殖潜力。
