基于卵泡液代谢组学的卵巢低反应生物标志物研究*

Research of biomarkers of poor ovarian response response based on follicular fluid metabolomics*

摘要:

目的 通过卵泡液代谢组学探寻与卵巢低反应相关的生物标志物。方法 采用超高液相色谱-高分辨质谱联用仪对行体外受精-胚胎移植/单精子卵泡浆内显微注射-胚胎移植（IVF-ET/ICSI-ET）的卵巢低反应组30例，以及同时仅因男方因素行IVF-ET/ICSI-ET的对照组49例进行卵泡液代谢组学分析。对比两组的差异代谢物。结果 与卵巢低反应相关的潜在生物标志物有30种，其上调的代谢物有9种，包括L-苯丙氨酸、脯氨酸、色氨酸、1-羟基-2-氧代丙基四氢蝶呤、水杨酸镁、尿苷二磷酸、LysoPC（18∶1）、LysoPC（18∶2）及LysoPC（18∶3）；下调的代谢物有21种，包括6-氧代己酸酯、亚油酸酯、油酸、十六烷、花生四烯酸、二十二碳六烯酸、13，14-二氢视黄醇、石胆酸、7-脱氢甾醇、硬脂酰肉碱、25-羟基维生素D3、 27-羟基胆固醇、3α，7α，12α-三羟基-5β-胆甾烷、13-羟基-α-生育酚、强啡肽A、LysoPC（16∶1）、LysoPC（16∶0）、LysoPC（18∶0）、LysoPC（20∶5）、LysoPC（20∶4）、LysoPC（20∶3）。结论 卵巢低反应患者在卵巢储备、卵巢反应、卵子数目、质量方面比正常女性低；卵巢低反应患者卵泡液代谢物与正常女性比较，差异有统计学意义（P?<0.05）。这些差异代谢物可以作为卵巢低反应的生物标志物。

Abstract:

Objective To explore biomarkers related to poor ovarian response based on follicular fluid metabolomics. Methods In vitro fertilization-embro transfer/intracy to plasmic sperm injection-embro transfer (IVF-ET/ICSI-ET) was performed by ultra-high liquid chromatography-high resolution mass spectrometry. 30 patients in the ovarian low-response group and 49 patients in the control group who received IVF-ET/ICSI-ET only due to male factors were analyzed for follicular fluid metabolomics, and the differential metabolites of the two groups were compared. Results This study found 30 potential biomarkers associated with low ovarian response. Upregulated metabolites included L-phenylalanine, proline, tryptophan, 1-hydroxy-2-oxypropyl tetrahydropterin, magnesium salicylate, uridine 5'-diphosphate, LysoPC (18 : 3), LysoPC (18 : 2) and LysoPC (18 : 1). Downregulated metabolites included 6-oxohexanoate, linoleate, oleic acid, hexadecanal, arachidonate, DHA, 13, 14-dihydroretinol, lithocholate, 7-dehydrodesmosterol, stearoylcarnitine, 25-hydroxyvitamin-D3, 27-hydroxycholestero and 3 alpha, 7 alpha and 12 alpha-Trihydroxy-5beta-cholestan-26-al, 13'-hydroxy-alpha-tocopherol, dynorphinA, LysoPC (16 : 1), LysoPC (16 : 0), LysoPC (18 : 0), LysoPC (20 : 5), LysoPC (20 : 4) and LysoPC (20 : 3). Conclusions Ovarian reserve, ovarian response, egg number and quality of patients with low ovarian response decrease compared with normal females; the follicular fluid metabolites of patients with low ovarian response were different from those of normal women, and the difference was statistically significant (P?