Early maternal undernutrition induces sex-related metabolic changes in adult offspring

Nutritional status during the developmental periods leads to predisposition to several diseases and comorbidities, highlighting metabolic and reproductive changes throughout adult life, and in the next generations. One of the experimental models used to induce undernutrition is litter size expansion, which decreases the availability of breast milk to pups and delays development. This work evaluated the effects of maternal undernutrition induced by litter size expansion, a maternal undernutrition preconception model, on the metabolic and reproductive alterations of the offspring. For this, metabolic and reproductive parameters were evaluated in male and female offspring of female rats reared in normal (NL - 10 pups: 5 males and 5 females) and large (LL - 16 pups: 8 males and 8 females) litters. Male and female offspring of LL mothers presented higher food intake than the offspring of NL mothers. Male offspring from undernourished females showed reduced body weight from lactation to adulthood, nasoanal distance in childhood, increased nasoanal distance, and decreased Lee index in adult life, while female offspring showed decreased nasoanal distance in childhood. The male offspring from LL mothers showed increased insulin plasma levels and glucose tolerance, and reduced triglycerides plasma levels, without changes in the female offspring. These results indicate that neonatal undernutrition in females predisposes their male and female offspring to develop metabolic alterations, without reproductive repercussions, and male offspring seems to be more susceptible to present these metabolic changes than females. Thus, there are sexual differences in the metabolic responses of the offspring elicited by maternal preconceptional undernutrition.