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This Article Full Text Full Text (PDF) All Versions of this Article: 294/2/R539    most recent 00628.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by O'Dowd, R. Articles by Wlodek, M. E. Search for Related Content PubMed PubMed Citation Articles by O'Dowd, R. Articles by Wlodek, M. E.

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

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

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

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