Gatti Cintia Romina, Schibert Florencia, Taylor Virginia Soledad, Capobianco Evangelina, Montero Verónica, Higa Romina, Jawerbaum Alicia
Universidad de Buenos Aires (UBA). Facultad de Medicina, Argentina; CONICET - UBA. Laboratory of Reproduction and Metabolism, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Buenos Aires, Argentina.
Hospital San Juan de Dios, Buenos Aires, Argentina.
Placenta. 2024 Nov 21. doi: 10.1016/j.placenta.2024.11.010.
Maternal diabetes increases the risk of adverse maternal, perinatal and offspring outcomes. This study aimed to address whether alterations in uterine decidualization are programmed in the prepubertal offspring from diabetic rats fed diets enriched or not in extra virgin olive oil (EVOO).
Control and mild pregestational diabetic female rats (F0) were mated with control males and fed diets enriched or not with 6 % EVOO during pregnancy. Offspring (F1) were evaluated on postnatal day 30, after induction of uterine decidualization (PMSG 50 IU- hCG 50 IU). Signaling pathways involved in decidualization, including prolactin, PPAR and mTOR pathways as well as microRNAs (miRs) regulating these pathways were evaluated by Western blot or qPCR in the decidualized uteri.
The offspring from diabetic rats evidenced reduced prolactin and prolactin receptor levels in the decidualized uteri. Additionally, these tissues showed increased PPARγ levels and reduced levels of its negative regulators miR-19b and miR-155. MiR-21, a microRNA that targets both PPARα and mTOR pathway regulators was reduced, whereas PPARα, PTEN and FOXO1 mRNA levels were increased in the decidualized uteri of the offspring from diabetic rats. The mTOR pathway activity was reduced in the decidualized uteri of the offspring from diabetic rats. Most of the observed alterations were prevented by the EVOO-enriched maternal diet.
Impaired pathways relevant to decidualization are programmed in the uteri of prepubertal offspring from diabetic dams, alterations capable of being prevented by maternal diets enriched in EVOO.
妊娠糖尿病会增加孕产妇、围产期及子代出现不良结局的风险。本研究旨在探讨在青春期前子代中，子宫蜕膜化的改变是否在孕期饲喂富含或不富含特级初榨橄榄油（EVOO）日粮的糖尿病大鼠中被编程。
将对照和轻度孕前糖尿病雌性大鼠（F0）与对照雄性大鼠交配，并在孕期饲喂富含或不富含6% EVOO的日粮。子代（F1）在出生后第30天，经诱导子宫蜕膜化（孕马血清促性腺激素50 IU - 人绒毛膜促性腺激素50 IU）后进行评估。通过蛋白质免疫印迹法或定量聚合酶链反应（qPCR）在蜕膜化子宫中评估参与蜕膜化的信号通路，包括催乳素、过氧化物酶体增殖物激活受体（PPAR）和雷帕霉素靶蛋白（mTOR）通路以及调节这些通路的微小RNA（miR）。
糖尿病大鼠的子代在蜕膜化子宫中催乳素和催乳素受体水平降低。此外，这些组织中PPARγ水平升高，其负调节因子miR - 19b和miR - 155水平降低。靶向PPARα和mTOR通路调节因子的miR - 21减少，而糖尿病大鼠子代的蜕膜化子宫中PPARα、磷酸酶和张力蛋白同源物（PTEN）及叉头框蛋白O1（FOXO1）的信使核糖核酸（mRNA）水平升高。糖尿病大鼠子代的蜕膜化子宫中mTOR通路活性降低。大多数观察到的改变可通过富含EVOO的母代日粮预防。
与蜕膜化相关的受损通路在糖尿病母代的青春期前子代子宫中被编程改变，这些改变可通过富含EVOO的母代日粮预防。
