INTRODUCTION: Diabetes mellitus is a metabolic pathology that leads to placental, fetal and offspring’s alterations. Little is known regarding putative alterations in the uteri of the offspring of diabetic mothers. Peroxisome proliferator activated receptors (PPARs) are nuclear receptors involved in metabolic, anti-inflammatory and developmental pathways. PPARs regulate the expression of prolactin, insulin like growth factor binding protein 1 (IGFBP1) and fatty acid binding protein 4 (FABP4), endocrine mediators of decidualization.
AIM: To address decidualization by evaluating the expression of genes codifying for PPARalpha, PPARgamma, prolactin and IGFBP1 and the protein levels of prolactin and FABP4 in the decidualized uteri of prepubertal offspring of diabetic and control rats.
METHODS: A mild pregestational diabetic rat model was induced in F0 females by neonatal administration of streptozotocin (90 mg/kg sc). Control and diabetic females were mated with healthy males. The uteri of the female offspring (F1) were evaluated on postnatal day 30, after induction of decidualization with PMSG (50 UI) and hCG (50 UI). In the decidualized uteri, Ppara, Pparg, Prl1 and Igfbp1 mRNA levels were evaluated by RT-qPCR and prolactin and FABP4 levels were evaluated by Western blot.
RESULTS: The offspring of diabetic rats showed an increase in Ppara mRNA levels compared to controls (0.84 fold-change, p<0.05) and an increase in Pparg mRNA levels (1.33 fold-change, p<0.05 vs Control Group) in the decidualized uteri. The Igfbp1 mRNA levels were increased in the decidualized uteri of the offspring from diabetic rats (2.5 fold-change, p<0.05 vs Control Group). Differently, the Prl1 mRNA levels were reduced in the decidualized uteri of the offspring from diabetic rats (0.38 fold-change, p<0.05 vs. Control Group). Prolactin protein levels were also reduced in the decidualized uteri of the offspring from diabetic rats (47%, p<0.05 vs Control Group). Differently, FABP4 levels were increased in the decidualized uteri of the offspring from diabetic rats (142%, p<0.01 vs Control Group).
CONCLUSIONS: The expression of Ppara and Pparg, as well as different proteins and genes involved in decidualization and regulated by these nuclear receptors, were altered in the decidualized uteri of diabetic rat offspring at a prepubertal stage. These alterations, evident at a prepubertal stage, may lead to reproductive impairments in the offspring of diabetic mothers.