Reducing Pup Litter Size Alters Early Postnatal Calcium Homeostasis and Programs Adverse Adult Cardiovascular and Bone Health in Male Rats.

Jessica F Briffa,Karen M Moritz,Tania Romano,Rachael O’Dowd,Mary E Wlodek,Beverly S Muhlhausler

doi:10.3390/nu11010118

Jessica F Briffa, Karen M Moritz + Show 4 more

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https://doi.org/10.3390/nu11010118

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Abstract

The in utero and early postnatal environments play essential roles in offspring growth and development. Standardizing or reducing pup litter size can independently compromise long-term health likely due to altered milk quality, thus limiting translational potential. This study investigated the effect reducing litter size has on milk quality and offspring outcomes. On gestation day 18, dams underwent sham or bilateral uterine vessel ligation surgery to generate dams with normal (Control) and altered (Restricted) milk quality/composition. At birth, pups were cross-fostered onto separate dams with either an unadjusted or reduced litter size. Plasma parathyroid hormone-related protein was increased in Reduced litter pups, whereas ionic calcium and total body calcium were decreased. These data suggest Reduced litter pups have dysregulated calcium homeostasis in early postnatal life, which may impair bone mineralization decreasing adult bone bending strength. Dams suckling Reduced litter pups had increased milk long-chain monounsaturated fatty acid and omega-3 docosahexaenoic acid. Reduced litter pups suckled by Normal milk quality/composition dams had increased milk omega-6 linoleic and arachidonic acids. Reduced litter male adult offspring had elevated blood pressure. This study highlights care must be taken when interpreting data from research that alters litter size as it may mask subtle cardiometabolic health effects.

Highlights

It is well known that the in utero and early postnatal environments play crucial roles in offspring growth, development and long-term health
We previously demonstrated that reducing the litter size of healthy Wistar Kyoto (WKY) rat dams at birth decreases offspring body weight during early life and increases adult male blood pressure likely due to mesenteric artery stiffness and compromises bone health [27,28,29,30,31]
Birth weight in the four experimental groups was not different and litter size was decreased in the groups that had their litter size Reduced at birth on postnatal day 1pups (PN1) and

Summary

Introduction

It is well known that the in utero and early postnatal environments play crucial roles in offspring growth, development and long-term health. Postnatal growth rate and development is directly proportional to the quality and quantity of milk produced and is influenced by fatty acid composition [11]. High intakes of omega-3 fatty acids in early postnatal life is associated with reduced fat deposition and improved cardiometabolic health [12,13]. More recent experimental studies have demonstrated that altered maternal nutrition during the lactation period can program adult offspring cardiometabolic disease. As milk is the sole source of nutrition during early postnatal life, these studies strongly support a role for altered milk quality and/or quantity as a mechanism through which maternal nutritional status during lactation influences offspring disease

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