Poor ovarian responders (POR) are women undergoing in-vitro fertilization who respond poorly to ovarian stimulation, resulting in the retrieval of lower number of oocytes, and subsequently lower pregnancy rates. The follicular fluid (FF) provides a crucial microenvironment for the proper development of follicles and oocytes. Conversely, dysregulated FF metabolome and cytokinome could have detrimental effects on oocytes in POR. Androgens such as dehydroepiandrosterone (DHEA) have been proposed to alter the POR follicular microenvironment but its effects on the FF metabolome and cytokine profiles is unknown. In this study, untargeted LC-MS/MS metabolomics was performed on FF of POR patients with DHEA supplementation (DHEA+) and without (DHEA-) in a randomized clinical trial (N=52). Untargeted metabolomics identified 118 FF metabolites of diverse chemistries, which included lipids, steroids, amino acids, hormones, among others. FF metabolomes were different between DHEA+ and DHEA- groups. Specifically, glycerophosphocholine, linoleic acid, progesterone, and valine were significantly lower in DHEA+ relative to DHEA-. Among cytokines, MCP1, IFNγ, LIF and VEGF-D were significantly lower in DHEA+ relative to DHEA. Collectively, our data suggest a role of DHEA on these metabolic and cytokines pathways, and these FF metabolites could be used to guide future studies in DHEA supplementation regimen.

中文翻译：

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卵巢反应不良者的卵泡液代谢组和细胞分裂素谱以及补充脱氢表雄酮的影响

卵巢反应不良（POR）是接受体外受精的妇女，她们对卵巢刺激的反应较弱，从而导致卵母细胞数量减少，从而降低了妊娠率。卵泡液（FF）为卵泡和卵母细胞的正常发育提供了至关重要的微环境。相反，失调的FF代谢组和细胞因子可能会对POR中的卵母细胞产生有害影响。已提出雄激素如脱氢表雄酮（DHEA）改变POR卵泡微环境，但其对FF代谢组和细胞因子谱的影响尚不清楚。在这项研究中，在一项随机临床试验（N = 52）中，对补充DHEA（DHEA +）和不补充（DHEA-）的POR患者的FF进行了非靶向LC-MS / MS代谢组学。非靶向代谢组学鉴定了118种不同化学性质的FF代谢产物，包括脂质，类固醇，氨基酸，激素等。DHEA +和DHEA-组之间的FF代谢组不同。具体而言，相对于DHEA-，DHEA +中的甘油磷酸胆碱，亚油酸，孕酮和缬氨酸明显较低。在细胞因子中，相对于DHEA，DHEA +中的MCP1，IFNγ，LIF和VEGF-D显着降低。总体而言，我们的数据表明DHEA在这些代谢和细胞因子途径中的作用，并且这些FF代谢物可用于指导DHEA补充方案的未来研究。与DHEA-相比，DHEA +中的缬氨酸和缬氨酸明显降低。在细胞因子中，DHEA +中的MCP1，IFNγ，LIF和VEGF-D显着低于DHEA。总体而言，我们的数据表明DHEA在这些代谢和细胞因子途径中的作用，并且这些FF代谢物可用于指导DHEA补充方案的未来研究。与DHEA-相比，DHEA +中的缬氨酸和缬氨酸明显降低。在细胞因子中，相对于DHEA，DHEA +中的MCP1，IFNγ，LIF和VEGF-D显着降低。总体而言，我们的数据表明DHEA在这些代谢和细胞因子途径中的作用，并且这些FF代谢物可用于指导DHEA补充方案的未来研究。