Division of Reproductive Endocrinology, Mayo Clinic, Rochester, MN 55905, USA.
Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN 55905, USA.
F S Sci. 2020 Aug;1(1):16-26. doi: 10.1016/j.xfss.2020.06.003. Epub 2020 Jun 29.
To determine how body mass index (BMI) affects the follicular fluid cytokine milieu and investigate how this inflammatory environment impacts cumulus signaling.
Experimental study.
Tertiary hospital based research laboratory.
Women with normal (18.5 to 24.9 kg/m) and obese (35 to 42 kg/m) BMI undergoing controlled ovarian stimulation for intracytoplasmic sperm injection (ICSI).
Cumulus cell treatment with obese follicular fluid, interleukin (IL) 10, and IL-1β.
Follicular fluid cytokine concentrations between normal and obese women were compared using multiplex bead assay. Differential cumulus cell gene expression of , , , and were measured using quantitative reverse polymerase chain reaction (RT-qPCR) while protein levels were determined by flow cytometry and confocal microscopy.
Compared to women with normal BMI, women with BMI ≥35 kg/m undergoing ICSI had higher follicular concentrations of IL-10 (9.46 pg/mL [0.59-19.16] vs 53.39 pg/mL [14.97-236.37], p=0.004) and IL-1β (1.92 pg/mL [1.92-5.18] vs 5.18 pg/mL [1.92-16.33], p=0.017), as well as decreased relative cumulus cell expression of (1.01 [0.66-1.40] vs 0.51 [0.38-0.74], p=0.03), a surrogate marker of positive ICSI outcomes. Furthermore, elevated IL-10 and IL-1β appear to be responsible for decreasing expression in women with BMI ≥35 kg/m.
Our findings suggest that follicular inflammation associated with obesity impacts cumulus cell signaling. At a molecular level, derangements to the immune system resulting in decreased expression may be a partial explanation for the suboptimal ICSI outcomes observed with obesity.
确定体重指数（BMI）如何影响卵泡液细胞因子环境，并研究这种炎症环境如何影响卵丘信号。
实验研究。
三级医院基础研究实验室。
接受体外受精（ICSI）的正常（18.5 至 24.9 kg/m）和肥胖（35 至 42 kg/m）BMI 妇女。
用肥胖卵泡液、白细胞介素（IL）10 和 IL-1β处理卵丘细胞。
采用多重珠粒检测法比较正常和肥胖妇女卵泡液细胞因子浓度。采用定量逆转录聚合酶链反应（RT-qPCR）测量卵丘细胞差异基因表达 、 、 ，并通过流式细胞术和共聚焦显微镜确定蛋白水平。
与 BMI 正常的妇女相比，BMI≥35 kg/m 接受 ICSI 的妇女卵泡中 IL-10（9.46 pg/mL[0.59-19.16] 与 53.39 pg/mL[14.97-236.37]，p=0.004）和 IL-1β（1.92 pg/mL[1.92-5.18] 与 5.18 pg/mL[1.92-16.33]，p=0.017）浓度更高，同时相对卵丘细胞表达的 （1.01[0.66-1.40] 与 0.51[0.38-0.74]，p=0.03）降低，这是 ICSI 结果阳性的替代标志物。此外，升高的 IL-10 和 IL-1β 似乎负责降低 BMI≥35 kg/m 妇女的 表达。
我们的研究结果表明，与肥胖相关的卵泡炎症会影响卵丘细胞信号。在分子水平上，免疫系统的紊乱导致 表达减少可能部分解释了肥胖与 ICSI 结果不佳的关系。
