Purpose

To utilize a novel mitochondrial function assay with pooled granulosa cells to determine whether mitochondrial function would differ by patient demographics and embryo development.

Methods

This was a prospective pilot study in a hospital-based assisted reproductive program and public university. Mitochondrial metabolic substrate utilization was assessed in pooled granulosa cells from 40 women undergoing in vitro fertilization during 2018 and 2019.

Results

Assessment of mitochondrial substrate metabolism in pooled granulosa cells revealed higher citric acid, L-malic acid, and octanoyl-L-carnitine utilization with higher body mass index (BMI). Utilization of citric acid, cis-aconitic acid, D-alpha-keto-glutaric acid, L-glutamine, and alanine plus glycine was significantly lower as total dosage of FSH administered increased. Utilization of glycogen was significantly higher in patients with a higher percentage of fertilized oocytes. D-alpha-keto-glutaric acid utilization was significantly lower in patients with a higher percentage of good 8-cell embryos. L-glutamine utilization was significantly lower, with a higher percentage of blastocyst formation. Mitochondrial metabolic scores (MMS), which reflect overall mitochondrial activity of the granulosa pool, were significantly higher in patients with higher BMI and with greater numbers of mature oocytes retrieved. MMS in granulosa decreased as total FSH dose administered increased.

Conclusions

Granulosa cell utilization of substrates feeding into the citric acid cycle changed with total FSH dosage and BMI. Fertilization rate, 8-cell embryo quality, and blastocyst formation also associated with different energy substrate usage. Mitochondrial substrate utilization by granulosa cells from individual follicles could be further developed into a useful diagnostic tool.

中文翻译：

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颗粒细胞中线粒体代谢底物的利用反映了体外受精患者的体重指数和总促卵泡激素剂量。

目的

使用一种新的线粒体功能测定与合并的颗粒细胞来确定线粒体功能是否会因患者人口统计学和胚胎发育而异。

方法

这是一项在医院辅助生殖项目和公立大学中进行的前瞻性试点研究。在 2018 年和 2019 年期间接受体外受精的 40 名女性的混合颗粒细胞中评估了线粒体代谢底物的利用率。

结果

对混合颗粒细胞中线粒体底物代谢的评估显示较高的柠檬酸、L-苹果酸和辛酰基-L-肉碱利用率与较高的体重指数 (BMI)。随着 FSH 总剂量的增加，柠檬酸、顺乌头酸、D-α-酮戊二酸、L-谷氨酰胺和丙氨酸加甘氨酸的使用显着降低。在受精卵母细胞百分比较高的患者中，糖原的利用率显着更高。D-α-酮戊二酸的利用率在具有较高比例的良好 8 细胞胚胎的患者中显着降低。L-谷氨酰胺利用率显着降低，囊胚形成的百分比更高。线粒体代谢评分（MMS），反映颗粒池的整体线粒体活性，在 BMI 较高和取回的成熟卵母细胞数量较多的患者中显着更高。随着总 FSH 剂量的增加，颗粒中的 MMS 减少。

结论

进入柠檬酸循环的底物的颗粒细胞利用随总 FSH 剂量和 BMI 变化。受精率、8 细胞胚胎质量和囊胚形成也与不同的能量底物使用有关。来自单个卵泡的颗粒细胞对线粒体底物的利用可以进一步发展成为一种有用的诊断工具。