Instituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS), University of Las Palmas de Gran Canaria (ULPGC), Spain.
Veterinary Histology and Pathology, Veterinary School, Institute of Animal Health, University of Las Palmas de Gran Canaria, Spain.
Reproduction. 2023 Aug 10;166(3):235-245. doi: 10.1530/REP-23-0024. Print 2023 Sep 1.
Fertility has decreased due to advanced maternal age and the rising prevalence of the metabolic syndrome. Using quantitative image analysis methods, we show that these factors are associated with delayed preimplantation embryo development in a mouse model.
Delayed maternal age, obesity and diabetes are associated with reduced fertility. We investigated how age and obesity/metabolic syndrome impact fertility and hypothesized that its decrease is due to defects in preimplantation embryo development. Three groups of female C57Bl6 mice (12 weeks, 9 months and 1 year old) were fed either a high-fat diet for 8 weeks, to induce obesity and the metabolic syndrome, or a control chow diet. Body weight and composition, glucose tolerance and insulin resistance were assessed. Fecundity was evaluated by mating and pregnancy rates, as well as by the number of embryos. Embryo quality was assessed morphologically, and cell fate composition was analysed in preimplantation embryos by state-of-the-art single-cell quantitative confocal image analysis. The high-fat diet was associated with increased adiposity, glucose intolerance and insulin resistance, especially in the older mice. Fecundity was affected by age more than by the diet. Both age and high-fat diet were associated with reduced cell fate allocation, indicating a delay in the preimplantation embryo development, and with increased expression of GATA3, an inhibitor of placentation. These results support that age and the metabolic syndrome reduce fertility through mechanisms which are present at conception or very early in pregnancy.
由于高龄产妇和代谢综合征的流行率上升，生育能力已经下降。通过使用定量图像分析方法，我们发现这些因素与小鼠模型中胚胎着床前发育延迟有关。
高龄、肥胖和糖尿病与生育能力下降有关。我们研究了年龄和肥胖/代谢综合征如何影响生育能力，并假设其下降是由于胚胎着床前发育缺陷所致。三组雌性 C57Bl6 小鼠（12 周、9 个月和 1 岁）分别用高脂肪饮食喂养 8 周，以诱导肥胖和代谢综合征，或用对照饲料喂养。评估体重和成分、葡萄糖耐量和胰岛素抵抗。通过交配和妊娠率以及胚胎数量评估生育能力。通过形态学评估胚胎质量，并通过最先进的单细胞定量共聚焦图像分析在胚胎着床前评估细胞命运组成。高脂肪饮食与肥胖、葡萄糖耐量和胰岛素抵抗增加有关，尤其是在老年小鼠中。年龄对生育能力的影响大于饮食。年龄和高脂肪饮食都与细胞命运分配减少有关，这表明胚胎着床前发育延迟，并与胎盘形成抑制剂 GATA3 的表达增加有关。这些结果表明，年龄和代谢综合征通过在受孕或妊娠早期就存在的机制降低生育能力。
