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The maternal endocrine environment in the low-protein model of intra-uterine growth restriction

Published online by Cambridge University Press:  09 March 2007

D. S. Fernandez-Twinn ,
S. E. Ozanne ,
S. Ekizoglou ,
C. Doherty ,
L. James ,
B. Gusterson  and
C. N. Hales
D. S. Fernandez-Twinn*
Affiliation:
Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QR, UK
S. E. Ozanne
Affiliation:
Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QR, UK
S. Ekizoglou
Affiliation:
Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QR, UK
C. Doherty
Affiliation:
Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QR, UK
L. James
Affiliation:
Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QR, UK
B. Gusterson
Affiliation:
Department of Pathology, Western Infirmary, University of Glasgow, Glasgow G11 6NT, Scotland, UK
C. N. Hales
Affiliation:
Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QR, UK
*
*Corresponding author: Dr D. S. Fernandez-Twinn, fax +44 1223 330598, email [email protected]
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Abstract

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Many adult diseases, including type 2 diabetes, hypertension and cardiovascular disease, are related to low birth weight. The mechanistic basis of this relationship is not known. To investigate the role of fetal undernutrition, we used a rat model of maternal protein restriction in which dams were fed a diet containing 80 g protein/kg (v. 200 g/kg in the control group) throughout gestation and lactation. Offspring were born smaller than controls and in adulthood developed diabetes, hyperinsulinaemia and tissue insulin resistance. To determine possible mechanisms of fetal programming, circulating levels of several hormones were measured in maternal plasma at gestational days 14, 17 and 21 and fetal plasma at gestational day 21. Several differences were noted at day 14, when glucose concentrations in maternal and feto–placental blood were raised significantly (P=0·04 and P=0·0001 respectively); insulin levels in the low-protein (LP) dams were raised (P=0·04), prolactin levels were raised (P=0·047) and progesterone levels were reduced (P=0·02). Circulating 17β-oestradiol in the LP dams was raised by 35% over those of the controls from day 17 to day 21 (P=0·008). A significant decrease in maternal leptin levels (P=0·004) was observed at gestation on day 21. Neither oestradiol nor leptin levels were altered in the fetal circulation at day 21. Maternal and fetal corticosterone levels were comparable with control levels, suggesting that they do not initiate the programming effects in this model. Our present results suggest that maternal protein restriction imposes changes in maternal levels of glucose, insulin, prolactin, progesterone, oestradiol and leptin; these changes could influence the programming of eventual adult disease in the developing fetus.

Keywords

Fetal programmingIntra-uterine growth restriction
Type
Research Article
Information
British Journal of Nutrition , Volume 90 , Issue 4 , October 2003 , pp. 815 - 822
Copyright
Copyright © The Nutrition Society 2003

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