title: Intergenerational programming of impaired nephrogenesis and hypertension in rats following maternal protein restriction during pregnancy.
abstract: Associations between birth weight and CVD in adult life are supported by experiments showing that undernutrition in fetal life programmes blood pressure. In rats, the feeding of a maternal low-protein (MLP) diet during gestation programmes hypertension. The present study aimed to assess the potential for a nutritional insult to impact across several generations. Pregnant female Wistar (F0) rats were fed a control (CON; n 10) or MLP (n 10) diet throughout gestation. At delivery all animals were fed a standard laboratory chow diet. At 10 weeks of age, F1 generation offspring were mated to produce a second generation (F2) without any further dietary change. The same procedure produced an F3 generation. Blood pressure in all generations was determined at 4, 6 and 8 weeks of age and nephron number was determined at 10 weeks of age. F1 generation MLP-exposed offspring exhibited raised (P < 0.001) systolic blood pressure (male 143 (sem 4) mmHg; female 141 (sem 4) mmHg) compared with CON animals (male 132 (sem 3) mmHg; female 134 (sem 4) mmHg). Raised blood pressure and reduced nephron number was also noted in the F2 generation (P < 0.001) and this intergenerational transmission occurred via both the maternal and paternal lines, as all three possible offspring crosses (MLP x CON, CON x MLP and MLP x MLP) were hypertensive (132 (sem 3) mmHg) compared with CON animals (CON x CON; 123 (sem 2) mmHg). No effect was noted in the F3 generation. It is concluded that fetal protein restriction may play a critical role in determining blood pressure and overall disease risk in a subsequent generation.
authors.affiliation: University of Nottingham, School of Biosciences, Sutton Bonington, Loughborough LE12 5RD, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Harrison
authors.forename: Simon C
authors.initials: SC
authors.lastname: Langley-Evans
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001823:Body Composition; D001947:Breeding; D002452:Cell Count; D002784:Cholesterol / Q000097:blood; D018753:Diet, Protein-Restricted; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D006973:Hypertension / Q000196:embryology* / Q000473:pathology; D007668:Kidney / Q000196:embryology* / Q000473:pathology; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D023421:Models, Animal; D009399:Nephrons / Q000473:pathology; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood
chemical_list: D004041:Dietary Fats; D014280:Triglycerides; D002784:Cholesterol
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