A Low Dose of Ouabain Alters the Metabolic Profile of Adult Rats Experiencing Intrauterine Growth Restriction in a Sex-Specific Manner

Intrauterine growth restriction (IUGR) increases the risk of type 2 diabetes mellitus (T2DM) and metabolic diseases. The pancreas of fetuses with IUGR is usually characterized by pancreatic dysplasia and reduced levels of insulin secretion caused by the diminished replication of β-cells. Previous studies showed that a low dose of ouabain could reduce the apoptosis of embryonic nephric cells during IUGR and partially restore the number of nephrons at birth. The rescued kidneys functioned well and decreased the prevalence of hypertension. Thus, we hypothesized that ouabain could rescue pancreatic development during IUGR and reduce the morbidity of T2DM and metabolic diseases. Maternal malnutrition was used to induce the IUGR model, and then a low dose of ouabain was administered to rats with IUGR during pregnancy. Throughout the experiment, we monitored the pattern of weight increase and evaluated the metabolic parameters in the offspring in different stages. Male, but not female, offspring in the IUGR group presented catch-up growth. Ouabain could benefit the impaired glucose tolerance of male offspring; however, this desirable effect was eliminated by aging. The insulin sensitivity was significantly impaired in male offspring with IUGR, but it was improved by ouabain, even during old age. However, in the female offspring, low birth weight appeared to be a beneficial factor even in old age; administering ouabain exacerbated these favorable effects. Our data suggested that IUGR influenced glucose metabolism in a sex-specific manner and ouabain treatment during pregnancy exerted strongly contrasting effects in male and female rats.