The oxylipins profile and their associations with embryo quality of women with polycystic ovary syndrome: a prospective cohort study

This study was aim to investigate the oxylipins profile in the follicular fluid (FF) of women with PCOS and examine their associations with embryo quality. We conducted a targeted lipidomic study involving sixty-two cases of PCOS and age-matched controls (Cohort 1) via UHPLC–MS. Cohort 2 included sixty cases of PCOS and age-and-BMI-matched controls who were recruited for validation via targeted lipidomics. The associations between these oxylipins and baseline hormones as well as embryo quality in PCOS patients were analyzed. A total of 59 oxylipins were identified in the FF of PCOS patients. In the FF of PCOS patients in Cohort 1, the level of 16(17)-EpDPE, a product derived from docosahexaenoic acid (DHA), was greater than that in the control group, even after adjustment for age, BMI and multiple comparisons (p p = 0.032). An increased concentration of 16(17)-EpDPE in women with PCOS was further validated in Cohort 2 (p p = 0.044). In addition, compared with the control group, the PCOS group in Cohort 2 presented significantly lower levels of eicosapentaenoic acid (EPA)-derived oxylipins (18-HEPE), DHA-derived oxylipins (4-HDoHE, 16-HDoHE), linoleic acid(LA)-derived oxylipins (12,13-EpOME, 13-HODE and 9-oxoODE), and dihomo-gamma-linolenic acid(DGLA)-derived oxylipins (15-HETrE). Correlation analyses between oxylipin metabolites and clinical features revealed that 16(17)-EpDPE was negatively associated with the number of D3 good-quality embryos and positively associated the blood lymphocyte count. Three LA-derived oxylipins were associated with the serum AMH and leptin levels in the FF. Our study revealed distinct metabolic signatures in women with PCOS and identified 16(17)-EpDPE as a novel biomarker for PCOS and their D3 good-quality embryos count.

本研究旨在探究多囊卵巢综合征（Polycystic Ovary Syndrome, PCOS）患者卵泡液（follicular fluid, FF）中的氧脂素（oxylipins）谱，并分析其与胚胎质量的关联。我们通过超高效液相色谱-质谱联用（Ultra High Performance Liquid Chromatography-Mass Spectrometry, UHPLC-MS）技术开展了一项靶向脂质组学研究，纳入队列1的62例多囊卵巢综合征患者及年龄匹配的对照个体。队列2纳入60例多囊卵巢综合征患者，以及年龄和体质量指数（Body Mass Index, BMI）匹配的对照个体，用于通过靶向脂质组学进行验证。本研究分析了多囊卵巢综合征患者体内这些氧脂素与基础激素水平及胚胎质量之间的关联。在多囊卵巢综合征患者的卵泡液中，共鉴定出59种氧脂素。在队列1的多囊卵巢综合征患者卵泡液中，二十二碳六烯酸（docosahexaenoic acid, DHA）衍生产物16(17)-EpDPE的水平高于对照组，即便在校正年龄、体质量指数及多重比较后（p=0.032）。队列2进一步验证了多囊卵巢综合征患者体内16(17)-EpDPE浓度升高这一现象（p=0.044）。此外，与对照组相比，队列2中的多囊卵巢综合征组二十碳五烯酸（eicosapentaenoic acid, EPA）衍生氧脂素18-HEPE、二十二碳六烯酸衍生氧脂素4-HDoHE、16-HDoHE、亚油酸（linoleic acid, LA）衍生氧脂素12,13-EpOME、13-HODE及9-oxoODE，以及二高-γ-亚麻酸（dihomo-gamma-linolenic acid, DGLA）衍生氧脂素15-HETrE的水平均显著降低。氧脂素代谢物与临床特征的相关性分析显示，16(17)-EpDPE与D3级优质胚胎数量呈负相关，与血液淋巴细胞计数呈正相关。三种亚油酸衍生氧脂素与血清抗缪勒管激素（anti-Müllerian hormone, AMH）及卵泡液中瘦素（leptin）水平相关。本研究揭示了多囊卵巢综合征患者独特的代谢特征，并确定16(17)-EpDPE可作为多囊卵巢综合征及其D3级优质胚胎数量的新型生物标志物。