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Am J Physiol Regul Integr Comp Physiol 294: R539-R548, 2008. First published December 12, 2007; doi:10.1152/ajpregu.00628.2007
0363-6119/08 $8.00
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DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Effects of uteroplacental insufficiency and reducing litter size on maternal mammary function and postnatal offspring growth

Rachael O'Dowd,1,* Jacqueline C. Kent,2 Jane M. Moseley,3 and Mary E. Wlodek1,*

1Department of Physiology, The University of Melbourne, Melbourne, Victoria; 2Biochemistry and Molecular Biology, The University of Western Australia, Crawley, Western Australia; and 3Department of Medicine, The University of Melbourne, Fitzroy, Victoria, Australia

Submitted 30 August 2007 ; accepted in final form 10 December 2007

Human intrauterine growth restriction is often associated with uteroplacental insufficiency and a decline in nutrient and oxygen supply to the fetus. This study investigated the effects of uteroplacental insufficiency and intrauterine growth restriction (Restricted) or reducing litter size for normally grown pups (Reduced Litter) on maternal mammary development and function, milk composition, offspring milk intake, and their resultant effects on postnatal growth. Uteroplacental insufficiency was surgically induced by bilateral uterine vessel ligation on day 18 of gestation in the Wistar Kyoto rat. At birth, a group of sham control rats had their litter size reduced to five (Reduced Litter) to match that of the Restricted group. Cohorts of rats were terminally anesthetized on day 20 of gestation or day 6 of lactation, and a third group was studied throughout lactation. Restricted pups had a lower birth weight (by 16%) and litter size (by 36%) compared with controls, as well as reduced mammary parathyroid hormone-related protein content and milk ionic calcium concentrations associated with reduced total pup calcium. Restricted dams with lower circulating progesterone experienced premature lactogenesis, producing less milk per pup with altered composition compared with controls, further slowing growth during lactation. Reducing litter size of pups born of normal birth weight (Reduced Litter) was associated with decreased pup growth, highlighting the importance of appropriate controls. The present study demonstrates that uteroplacental insufficiency impairs mammary function, compromises milk quality and quantity, and reduces calcium transport into milk, further restraining postnatal growth.

growth restriction; mammary gland; programming; parathyroid hormone-related protein


Address for reprint requests and other correspondence: M. E. Wlodek, Dept. of Physiology, Univ. of Melbourne, Melbourne, Victoria 3010, Australia (e-mail: m.wlodek{at}unimelb.edu.au)






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