1 Division of Reproductive Endocrinology and Infertility and the Cecil H and Ida Green Center for Reproductive Biological Sciences, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Reprod Sci. 2019 Mar;26(3):404-411. doi: 10.1177/1933719118776787. Epub 2018 May 20.
Obesity is an epidemic affecting more than one-third of adults in the United States. Obese women experience decreased fertility, explained in part by oocyte quality. Since follicular fluid (FF) provides an important microenvironment for oocyte growth, we sought to evaluate the effect of increased body weight on FF levels of 11 metabolic hormones and fatty acid metabolism.
The FF was collected from 25 women (10 normal weight, 10 overweight, and 5 obese) with diminished ovarian reserve undergoing in vitro fertilization (IVF) following a minimal stimulation protocol. Hormone levels were determined by multiplex immunoassay using the MAGPIX (Luminex, Austin, Texas) instrument. Fatty acid metabolites were determined using gas and ultra-high pressure liquid chromatography coupled with mass spectrometry.
Levels of hormones related to glucose and energy homeostasis and regulation of fat stores (insulin, glucagon, glucagon-like peptide-1, C-peptide, and leptin) were increased significantly in FF from obese women compared to FF from nonobese(normal weight and overweight) women. Interestingly, FF levels of branched-chain amino acids (BCAA) isoleucine, leucine, and valine as well as uric acid, isocaproic acid, butanoic acid, tyrosine, threonine, glycine, and methionine correlated positively with body mass index.
This pilot study demonstrates significant alterations in the FF milieu of obese women undergoing IVF, which may contribute to the decreased fecundity of obese women. Although the impact of this environment on oocyte and embryo development is not fully realized, these changes may also lead to imprinting at the genomic level and long-term sequelae on offspring.
肥胖是一种在美国影响超过三分之一成年人的流行疾病。肥胖女性的生育能力下降，部分原因是卵母细胞质量下降。由于卵泡液 (FF) 为卵母细胞生长提供了重要的微环境，我们试图评估体重增加对 FF 中 11 种代谢激素和脂肪酸代谢水平的影响。
从 25 名卵巢储备功能降低的接受体外受精 (IVF) 的女性（10 名正常体重、10 名超重和 5 名肥胖）的 FF 中收集样本，这些女性采用最小刺激方案。使用 MAGPIX（Luminex，德克萨斯州奥斯汀）仪器通过多重免疫测定法测定激素水平。使用气相和超高效液相色谱-质谱联用技术测定脂肪酸代谢物。
与非肥胖（正常体重和超重）女性的 FF 相比，肥胖女性 FF 中与葡萄糖和能量稳态以及脂肪储存调节相关的激素（胰岛素、胰高血糖素、胰高血糖素样肽 1、C 肽和瘦素）水平显著升高。有趣的是，FF 中支链氨基酸 (BCAA) 异亮氨酸、亮氨酸和缬氨酸以及尿酸、异己酸、丁酸、酪氨酸、苏氨酸、甘氨酸和蛋氨酸的水平与体重指数呈正相关。
这项初步研究表明，接受 IVF 的肥胖女性的 FF 环境发生了显著变化，这可能导致肥胖女性生育能力下降。尽管这种环境对卵母细胞和胚胎发育的影响尚未完全实现，但这些变化也可能导致基因组水平的印迹和后代的长期后遗症。
