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Gestational dietary protein is associated with sex specific decrease in blood flow, fetal heart growth and post-natal blood pressure of progeny

Hernandez Medrano, Juan; Copping, Katrina J.; Hoare, Andrew; Wapanaar, Wendela; Grivell, Rosalie; Kuchel, Tim; Miguel-Pacheco, Giuliana; McMillen, I. Caroline; Rodgers, Raymond J.; Perry, Viv E.A.


Juan Hernandez Medrano

Katrina J. Copping

Andrew Hoare

Wendela Wapanaar

Rosalie Grivell

Tim Kuchel

Giuliana Miguel-Pacheco

I. Caroline McMillen

Raymond J. Rodgers

Viv E.A. Perry


The incidence of adverse pregnancy outcomes is higher in pregnancies where the fetus is male. Sex specific differences in feto-placental perfusion indices identified by Doppler assessment have recently been associated with placental insufficiency and fetal growth restriction. This study aims to investigate sex specific differences in placental perfusion and to correlate these changes with fetal growth. It represents the largest comprehensive study under field conditions of uterine hemodynamics in a monotocous species, with a similar long gestation period to the human. Primiparous 14mo heifers in Australia (n=360) and UK (n=180) were either individually or group fed, respectively, diets with differing protein content (18, 14, 10 or 7% crude protein (CP)) from 60d prior to 98 days post conception (dpc). Fetuses and placentae were excised at 98dpc (n = 48). Fetal development an median uterine artery blood flow were assessed monthly from 36dpc until term using B-mode and Doppler ultrasonography. MUA blood flow to the male feto-placental unit increased in early pregnancy associated with increased fetal growth. Protein restriction before and shortly after conception (-60d up to 23dpc) increased MUA diameter and indices of velocity during late pregnancy, reduced fetal heart weight in the female fetus and increased heart rate at birth, but decreased systolic blood pressure at six months of age.

Conclusion and Significance
Sex specific differences both in feto-placental Doppler perfusion indices and response of these indices to dietary perturbations were observed. Further, maternal diet affected development of fetal cardiovascular system associated with altered fetal haemodynamics in utero, with such effects having a sex bias. The results from this study provide further insight into the gender specific circulatory differences present in the fetal period and developing cardiovascular system


Hernandez Medrano, J., Copping, K. J., Hoare, A., Wapanaar, W., Grivell, R., Kuchel, T., …Perry, V. E. (2015). Gestational dietary protein is associated with sex specific decrease in blood flow, fetal heart growth and post-natal blood pressure of progeny. PLoS ONE, 10(4), Article e0197942.

Journal Article Type Article
Acceptance Date Mar 19, 2015
Online Publication Date Apr 27, 2015
Publication Date Apr 29, 2015
Deposit Date Apr 16, 2018
Publicly Available Date Aug 15, 2019
Journal PLoS ONE
Electronic ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 10
Issue 4
Article Number e0197942
Public URL
Publisher URL
PMID 25915506


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