Valckx Sara D M, Van Hoeck Veerle, Arias-Alvarez Maria, Maillo Veronica, Lopez-Cardona Angela P, Gutierrez-Adan Alfonso, Berth Mario, Cortvrindt Rita, Bols Peter E J, Leroy Jo L M R
Gamete Research Center, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Wilrijk, Belgium.
Gamete Research Center, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Wilrijk, Belgium.
Fertil Steril. 2014 Dec;102(6):1769-76.e1. doi: 10.1016/j.fertnstert.2014.08.018. Epub 2014 Sep 23.
To study how long-term elevated non-esterified fatty acid (NEFA) concentrations, typical in metabolic disorders such as obesity or type 2 diabetes, affect murine follicular development, follicle quality, and subsequent oocyte developmental competence in vitro.
Experimental study.
In vitro culture setting.
ANIMAL(S): Female and male 13-day old, B6CBAF1 mice of proven fertility were sacrificed for harvesting ovaries and epididymal sperm, respectively.
INTERVENTION(S): Early secondary murine follicles were cultured in vitro in the presence of NEFAs until the antral stage (12 days). Treatments consisted of one or a mixture of NEFAs (stearic acid [SA], palmitic acid [PA], oleic acid [OA]) in physiological (basal) or pathological (high SA, high OA, high NEFA) concentrations.
MAIN OUTCOME MEASURE(S): Follicular development; follicle and oocyte diameters; secretion of progesterone, estradiol, and inhibin B; and luteinized granulosa cell gene expression patterns were investigated. Oocytes from NEFA-exposed follicles were fertilized in vitro, and presumptive zygotes were cultured until the blastocyst stage.
RESULT(S): Exposure to high SA reduced follicle diameters and day-12 antrum formation. Elevated NEFA concentrations changed luteinized granulosa cell messenger-ribonucleic acid abundance of genes related to energy/fatty acid/steroid metabolism, apoptosis, and oxidative stress. High NEFA and high SA treatments increased progesterone synthesis, compared with high OA follicles. Oocyte developmental competence was substantially reduced in oocytes retrieved from high OA-, high SA-, and high NEFA-exposed follicles compared with basal-treated follicles.
CONCLUSION(S): This study showed, for the first time, that lipolysis-linked, elevated NEFA concentrations can potentially impair fertility, by altering follicular physiology and reducing oocyte developmental competence.
研究在肥胖或2型糖尿病等代谢紊乱中常见的长期升高的非酯化脂肪酸（NEFA）浓度如何影响小鼠卵泡发育、卵泡质量以及随后的卵母细胞体外发育能力。
实验研究。
体外培养环境。
处死13日龄、已证实具有生育能力的雌性和雄性B6CBAF1小鼠，分别获取卵巢和附睾精子。
将早期次级小鼠卵泡在存在NEFA的情况下体外培养至窦状卵泡阶段（12天）。处理包括生理（基础）或病理（高SA、高OA、高NEFA）浓度的一种NEFA或NEFA混合物（硬脂酸[SA]、棕榈酸[PA]、油酸[OA]）。
研究卵泡发育；卵泡和卵母细胞直径；孕酮、雌二醇和抑制素B的分泌；以及黄体化颗粒细胞基因表达模式。将来自暴露于NEFA的卵泡的卵母细胞进行体外受精，并将假定的合子培养至囊胚阶段。
暴露于高SA会降低卵泡直径和第12天窦腔形成。升高的NEFA浓度改变了与能量/脂肪酸/类固醇代谢、细胞凋亡和氧化应激相关基因的黄体化颗粒细胞信使核糖核酸丰度。与高OA卵泡相比,高NEFA和高SA处理增加了孕酮合成。与基础处理的卵泡相比，从暴露于高OA、高SA和高NEFA的卵泡中获取的卵母细胞的发育能力显著降低。
本研究首次表明，与脂肪分解相关的升高的NEFA浓度可能通过改变卵泡生理和降低卵母细胞发育能力而损害生育能力。
