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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.

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