UTEROPLACENTAL INSUFFICIENCY IMPAIRS MAMMARY FUNCTION AND PERINATAL GROWTH: A CROSS FOSTERING STUDY

Urszula Lorenc¹, Rachael O'Dowd¹, Irene Koukoulas³, Karen Moritz³, Angela Gibson³, Patricia W.M. Ho², Jane M. Moseley², Mary E. Wlodek¹, 1 Department of Physiology, University of Melbourne, Parkville, Vic, 3010, 2 Department of Medicine and St Vincent's Institute of Medical Research, Fitzroy, Vic, 3065, 3 Howard Florey Institute of Experimental Physiology and Medicine, Parkville, Vic, 3010.

In many human and experimental models of intrauterine growth restriction, prenatal and postnatal growth are impaired and some are associated with catch up growth. Parathyroid Hormone-related Protein (PTHrP) is thought to play a role in altering prenatal and postnatal growth by its actions on placental and mammary function. During lactation PTHrP has been suggested to have important functions including: the stimulation of mammary epithelial growth and differentiation; increasing calcium transport from blood to milk; and regulation of mammary blood flow and myoepithelial cell tone. Bilateral uterine artery and vein vessel ligation (BUVL) reduces uteroplacental blood flow causing growth restriction and therefore mimics features of human growth restriction. The aim of this study was to determine the relative roles of the prenatal and postnatal environments on postnatal growth and mammary function. BUVL or sham surgery was preformed on day 18 of gestation in Wistar Kyoto rats. Pups were cross fostered at birth and tissues, plasma, milk and weights were collected 6 days postnatally. Data were analysed by ANOVA (n=4-8 per group). BUVL-on-BUVL pup weight and mammary weight were significantly lower than Sham-on-Sham (p<0.01). The cross fostered groups (BUVL-on-Sham and Sham-on-BUVL) had intermediate pup and mammary weights compared to BUVL-on-BUVL and Sham-on-Sham (p<0.01) indicating that both the pup and mammary function contributed to postnatal growth. Mammary PTHrP content was significantly greater for Sham pups compared to BUVL pups, irrespective of their mother (p<0.007). This suggests that growth restricted BUVL pups are unable to stimulate normal mammary PTHrP production. There were no significant differences in maternal plasma PTHrP and calcium concentrations. Placental insufficiency therefore impairs perinatal growth as well as mammary function. This study suggests that both the pup and maternal mammary function contribute to postnatal growth and indicates that mammary function may be an important mediator of catch up growth in growth restricted infants.