Short- and long-term effects of maternal perinatal undernutrition are lowered by cross-fostering during lactation in the male rat

Abstract

Undernutrition exposure during the perinatal period reduces the growth kinetic of the offspring and sensitizes it to the development of chronic adult metabolic diseases both in animals and in humans. Previous studies have demonstrated that a 50% maternal food restriction performed during the last week of gestation and during lactation has both short- and long-term consequences in the male rat offspring. Pups from undernourished mothers present a decreased intrauterine (IUGR) and extrauterine growth restriction. This is associated with a drastic reduction in their leptin plasma levels during lactation, and exhibit programming of their stress neuroendocrine systems (corticotroph axis and sympatho-adrenal system) in adulthood. In this study, we report that perinatally undernourished 6-month-old adult animals demonstrated increased leptinemia (at PND200), blood pressure (at PND180), food intake (from PND28 to PND168), locomotor activity (PND187) and altered regulation of glycemia (PND193). Cross-fostering experiments indicate that these alterations were prevented in IUGR offspring nursed by control mothers during lactation. Interestingly, the nutritional status of mothers during lactation (ad libitum feeding v. undernutrition) dictates the leptin plasma levels in pups, consistent with decreased leptin concentration in the milk of mothers subjected to perinatal undernutrition. As it has been reported that postnatal leptin levels in rodent neonates may have long-term metabolic consequences, restoration of plasma leptin levels in pups during lactation may contribute to the beneficial effects of cross-fostering IUGR offspring to control mothers. Collectively, our data suggest that modification of milk components may offer new therapeutic perspectives to prevent the programming of adult diseases in offspring from perinatally undernourished mothers.

Maternal perinatal undernutrition modifies lactose and serotranferrin in milk: relevance to the programming of metabolic diseases?

“…Taken together, these results provide new information in milk composition from young undernourished rat mothers (60 days old). Although milk production was not directly measured in the present study, several arguments suggest that maternal perinatal undernutrition also decreases milk quantity: 1) milk from undernourished mothers is more concentrated and thus less hydrated, reflecting a reduction of milk volume; 2) cross-fostering of control pups by undernourished mothers also led to reduced kinetic of growth, whereas FR50 pups nursed by control mothers exhibited a weight gain similar to control pups, suggesting that maternal nutrition does not modify feeding behavior in rat neonates (53); and 3) lactose, the main sugar in most mammalian species, is reduced in the milk of undernourished mothers. It is known to be the primary osmotic agent that attracts water in the milky secretion, and is thus considered as the major determinant of milk volume (36).…”

“…Breast milk is known to contain many bioactive factors (2) involved in the development and growth as well as in the maturation of the immune system and gut microbiota (13,27). We have recently shown that cross-fostering by control mothers of IUGR pups prevents the development of hyperphagia, hypertension, and intolerance to glucose observed in perinatally food-restricted adult male rats (53). Interestingly, maternal nutritional status during lactation influences leptin concentration both in milk and in the plasma of pups (53).…”

“…We have recently shown that cross-fostering by control mothers of IUGR pups prevents the development of hyperphagia, hypertension, and intolerance to glucose observed in perinatally food-restricted adult male rats (53). Interestingly, maternal nutritional status during lactation influences leptin concentration both in milk and in the plasma of pups (53). Because neonatal leptin levels have been demonstrated to play an important neurodevelopmental role (7,16), our data strongly suggest that the milk composition may participate to the programming of metabolic diseases in adulthood.…”

Maternal Caloric Restriction prior to Pregnancy Increases the Body Weight of the Second-Generation Male Offspring and Shortens Their Longevity in Rats

“…Some studies have suggested the compensatory effects of prenatal undernutrition with adequate postnatal nutrition or hormonal therapy (Reynolds et al 2013;Wattez et al 2014), whereas other authors remain quite pessimistic. Animal research shows that a spare diet from a young age might be helpful in preventing age induced damage on pancreatic β cells (He et al 2012).…”

Primary Pediatric Hypertension: Current Understanding and Emerging Concepts

“…Maternal protein restriction leads to sympathetic overactivity and oxidative dysfunction at the medulla oblongata of Wistar rat dams [54]. There is an increase in circulating leptin in the adult offspring [55]; leptin can stimulate the sympathetic nervous system in rodents [56•]. Chronic administration of leptinin humans does not increase BP [56•].…”