Maternal vitamin D administration attenuates metabolic disturbances induced by prenatal exposure to dexamethasone in a sex-dependent manner

Autor: Alex Rafacho, Gustavo J. Santos, Fernanda B. Lima, Rafaela C.K. Stolte, Fernanda Niebisch, Flaviano Lorenzon, Tamires Gregorio
Rok vydání: 2021
Předmět:
Zdroj: The Journal of Steroid Biochemistry and Molecular Biology. 212:105941
ISSN: 0960-0760
DOI: 10.1016/j.jsbmb.2021.105941
Popis: Purpose The overexposure to synthetic glucocorticoids (GC) during pregnancy can predispose to metabolic diseases during adulthood. Vitamin D is not only crucial for fetal development, but also exerts direct effects on the GC sensitivity and down-regulates GC receptors. Given the vitamin D effects on glucocorticoid-related parameters, we aimed to investigate a possible protective role of maternal vitamin D administration on the glucose homeostasis of rats exposed to dexamethasone in utero. Methods Pregnant rats received dexamethasone (0.1 mg/kg, Dex) daily between the 14th and 19th days of pregnancy. A subgroup of dexamethasone-treated dams received oral administration of vitamin D (500UI, DexVD) during the whole gestation. The corresponding control groups of dams were included (CTL and VD groups, respectively). Male and female offspring were evaluated at 3, 6 and 12 months of age. Results Prenatal exposure to dexamethasone caused metabolic disruption in an age and sex-dependent manner being the older male offspring more susceptible to insulin resistance, fatty liver and beta-cell mass expansion than females. Furthermore, we demonstrated that prenatal GC led to glucose intolerance in male and female offspring in an age-dependent manner. Maternal vitamin D administration did not influence glucose intolerance but attenuated the insulin resistance, liver lipid accumulation and prevented the beta-cell mass expansion caused by prenatal dexamethasone in the male offspring. Conclusion Maternal vitamin D administration mitigates metabolic disturbances that occur later in life in male rats exposed to GC in utero. Moreover, our data suggest vitamin D as an important nutritional supplement for pregnant overexposed to GC during gestation.
Databáze: OpenAIRE