Yan Shi, Wang Fengjuan, Shi Qingyun
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, P.R. China.
Department of Obstetrics and Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, P.R. China.
Exp Ther Med. 2020 Dec;20(6):135. doi: 10.3892/etm.2020.9264. Epub 2020 Oct 2.
A maternal high-fat diet (HFD) has been shown to exert deleterious effects on fetal programming by impairing embryo growth, and exerts a long-term effect on the health of offspring. The present study aimed to evaluate the effect of a maternal HFD on the ovaries of offspring from the perspective of oxidative stress. Female C57BL/6J mice were randomly assigned to four groups fed various HFDs during the preconception (4 weeks) and gestation-lactation periods. Offspring were fed a normal diet after weaning, and serum and ovaries were collected at 10 weeks of age. The developmental status of follicles was observed using hematoxylin and eosin staining. The serum oxidative stress levels and insulin resistance were detected using ELISA test kits. The expression of phosphorylated form of H2AX histone variant (γH2AX), forkhead box protein O3a (FOXO3a), Bcl-2-like protein 11 (Bim)and insulin-like growth factor (IGF)-1 in ovarian tissue was analyzed using reverse transcription-quantitative PCR and western blot analyses to further explore the pathogenic mechanism. Prenatal exposure to a maternal HFD resulted in a reduced number of primordial and preantral follicles in the ovaries of offspring. Exposure to an HFD in the preconception period exerted a greater effect on the offspring compared with exposure to an HFD in the gestation-lactation period. A reduction in fat intake during the preconception, gestation and lactation periods significantly reduced the associated adverse outcomes. The expression of genes (, , and ) involved in oxidative stress showed a decreasing trend (high-fat/high-fat>high-fat/control>control/high-fat >control/control) in the ovaries of offspring. Overall, HFD exposure during the preconception period exerted a greater effect on offspring compared with HFD exposure during the gestation-lactation period. The long-term effect on follicular growth and development may be associated with increased oxidative stress and the activation of the insulin/PI3K/Akt pathway.
母体高脂饮食（HFD）已被证明会通过损害胚胎生长对胎儿编程产生有害影响，并对后代健康产生长期影响。本研究旨在从氧化应激的角度评估母体高脂饮食对后代卵巢的影响。将雌性C57BL/6J小鼠随机分为四组，在孕前（4周）以及妊娠-哺乳期给予不同的高脂饮食。后代断奶后给予正常饮食，并在10周龄时收集血清和卵巢。使用苏木精和伊红染色观察卵泡的发育状态。使用ELISA试剂盒检测血清氧化应激水平和胰岛素抵抗。采用逆转录定量PCR和蛋白质免疫印迹分析卵巢组织中组蛋白变体H2AX的磷酸化形式（γH2AX）、叉头框蛋白O3a（FOXO3a）、Bcl-2样蛋白11（Bim）和胰岛素样生长因子（IGF）-1的表达，以进一步探究其致病机制。产前暴露于母体高脂饮食会导致后代卵巢中原始卵泡和窦前卵泡数量减少。与在妊娠-哺乳期暴露于高脂饮食相比，孕前暴露于高脂饮食对后代的影响更大。在孕前、妊娠和哺乳期减少脂肪摄入可显著降低相关不良后果。后代卵巢中参与氧化应激的基因（ 、 、 和 ）表达呈下降趋势（高脂/高脂>高脂/对照>对照/高脂>对照/对照）。总体而言，与妊娠-哺乳期暴露于高脂饮食相比，孕前暴露于高脂饮食对后代的影响更大。对卵泡生长发育的长期影响可能与氧化应激增加和胰岛素/PI3K/Akt信号通路激活有关。
