Roberti Sabrina Lorena, Gatti Cintia Romina, Fornes Daiana, Higa Romina, Jawerbaum Alicia
Universidad de Buenos Aires, Facultad de Medicina, Buenos Aires, Argentina; CONICET-Universidad de Buenos Aires, Laboratory of Reproduction and Metabolism, CEFYBO, Buenos Aires, Argentina.
Universidad de Buenos Aires, Facultad de Medicina, Buenos Aires, Argentina; CONICET-Universidad de Buenos Aires, Laboratory of Reproduction and Metabolism, CEFYBO, Buenos Aires, Argentina.
J Nutr Biochem. 2021 Sep;95:108765. doi: 10.1016/j.jnutbio.2021.108765. Epub 2021 May 6.
Maternal diabetes increases the risk of embryo resorptions and impairs embryo development. Decidualization is crucial for embryo development and regulated by mTOR signaling. However, little is known about how maternal diabetes affects the decidua at early postimplantation stages and whether dietary treatments enriched in polyunsaturated fatty acids (PUFAs) can prevent decidual alterations. Here, we determined resorption rates, decidual mTOR pathways and markers of decidual function and remodeling in diabetic rats fed or not with diets enriched in PUFAs exclusively during the early postimplantation period. Pregestational streptozotocin-induced diabetic Albino Wistar rats and controls were fed or not with diets enriched in 6% sunflower oil or 6% chia oil (enriched in n-6 or n-3 PUFAs, respectively) on days 7, 8 and 9 of pregnancy and evaluated on day 9 of pregnancy. Maternal diabetes induced an 11-fold increase in embryo resorptions, which was prevented by both PUFAs-enriched diets despite no changes in maternal glycemia. The activity of mTOR pathway was decreased in the decidua from diabetic rats, an alteration prevented by the PUFAs-enriched diets. PUFAs-enriched diets prevented increased expression of Foxo1 (a negative regulator of mTOR) and reduced expression of miR-21 (a negative regulator of Foxo1). These diets also prevented reduced markers of decidual function (leukemia inhibitory factor and IGFBP1 expression and MMPs activity) in diabetic rat decidua. We identified the early post implantation as a crucial stage for pregnancy success, in which dietary PUFAs can protect diabetic pregnancies from embryo resorptions, decidual mTOR signaling impairments, and altered markers of decidual function and remodeling.
母体糖尿病会增加胚胎吸收的风险并损害胚胎发育。蜕膜化对胚胎发育至关重要,并受mTOR信号通路调控。然而,关于母体糖尿病如何影响着床后早期的蜕膜,以及富含多不饱和脂肪酸(PUFA)的饮食治疗是否能预防蜕膜改变,我们知之甚少。在此,我们测定了仅在着床后早期用富含PUFA的饮食或不用该饮食喂养的糖尿病大鼠的吸收速率、蜕膜mTOR通路以及蜕膜功能和重塑的标志物。对妊娠前用链脲佐菌素诱导的糖尿病白化Wistar大鼠和对照组在妊娠第7、8和9天分别给予富含6%葵花籽油或6%奇亚籽油(分别富含n-6或n-3 PUFA)的饮食或不给予,在妊娠第9天进行评估。母体糖尿病使胚胎吸收增加了11倍,尽管母体血糖没有变化,但两种富含PUFA的饮食都能预防这种情况。糖尿病大鼠蜕膜中mTOR通路的活性降低,而富含PUFA的饮食可预防这种改变。富含PUFA的饮食可预防Foxo1(mTOR的负调节因子)表达增加和miR-21(Foxo1的负调节因子)表达降低。这些饮食还可预防糖尿病大鼠蜕膜中蜕膜功能标志物(白血病抑制因子和IGFBP1表达以及MMPs活性)的降低。我们确定着床后早期是妊娠成功的关键阶段,在此阶段,饮食中的PUFA可保护糖尿病妊娠免受胚胎吸收、蜕膜mTOR信号受损以及蜕膜功能和重塑标志物改变的影响。