Protection of cumulus cells following dehydroepiandrosterone supplementation

Abstract

Background: Growing studies have demonstrated that dehydroepiandrosterone (DHEA) may improve fertility outcomes in poor ovarian responders (PORs). The aim of this study was to compare clinical outcomes and cumulus cell (CC) expression before and after DHEA treatment in PORs undergoing in vitro fertilization (IVF) cycles.

Methods: Six patients with poor ovarian response were enrolled in the study according to Bologna criteria. DHEA was supplied at least 2 months before patients entered into the next IVF cycle. Expression of apoptosis-related genes in CCs was determined by quantitative real-time PCR. Mitochondrial dehydrogenase activity of CCs was assessed by cell counting kit-8 assay.

Results: Metaphase II oocytes, maturation rate, embryos at Day 3, and fertilization rate significantly increased following DHEA treatment. Expression of cytochrome c, caspase 9, and caspase 3 genes in CCs were significantly reduced after DHEA therapy. Additionally, increased mitochondrial activity of CCs was observed following DHEA supplementation.

Conclusions: DHEA supplementation may protect CCs via improved mitochondrial activity and decreased apoptosis, leading to better clinical outcomes in PORs.

Chinese abstract

研究背景: 越来越多的研究表明, 脱氢表雄酮 (DHEA) 可改善卵巢低反应患者的生育能力。本研究主要目的为比较应用DHEA治疗方案前后, 处于体外受精 (IVF) 周期内的卵巢低反应患者的预后和卵丘细胞 (CC) 表达情况。

方法: 6位符合博洛尼亚低反应标准的卵巢低反应患者参与本研究。在下次体外受精周期前至少2月行DHEA治疗。应用实时定量PCR技术和CCK-8分别检测卵丘细胞内凋亡相关基因的表达和线粒体脱氢酶活性。

结果: 经DHEA治疗后, M II期卵母细胞数目、成熟率、第3日胚胎数目和受精率均有显著增长；而卵丘细胞内细胞色素c, caspase9和caspase3基因的表达均明显降低。此外, 卵丘细胞的线粒体活性也在补充DHEA后增加。

结论: 补充DHEA后, 通过改善线粒体活性和减少细胞凋亡的发生可保护卵丘细胞, 进而让卵巢低反应患者有更好的预后。

Keywords:

• Apoptosis
• cumulus cells
• dehydroepiandrosterone
• mitochondria
• poor ovarian responder

Declaration of interest

The authors declare no conflict of interest.

This work was generously supported by grant VGHKS105-G06-01 from from Kaohsiung Veterans General Hospital.

Paper presentation information

All the authors declare that we have not submitted this work for publication elsewhere.

Authors’ roles

L.-T.L. is responsible for data extraction and drafting the article. P.-H.W. and S.-N.C. are responsible for analysis and interpretation of data. C.-J.L. and Z.-H.W. are responsible for design of the study and acquisition of data. J.-T.C. and K.-H.T. are responsible for revising the manuscript and final approval of the version to be submitted.

Supplementary material available online