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Intergenerational programming of impaired nephrogenesis and hypertension in rats following maternal protein
Matthew Harrison1, Simon C Langley-Evans
1University of Nottingham, School of Biosciences, Sutton Bonington, Loughborough LE12 5RD, UK.
Insights
Maternal low-protein (MLP) diet in pregnant rats programmed hypertension in offspring. This effect persisted into the second generation, highlighting how fetal nutrition impacts cardiovascular health across generations.
Area of Science:
- Developmental Biology
- Cardiovascular Physiology
- Nutritional Science
Background:
- Fetal undernutrition is linked to adult cardiovascular disease (CVD).
- Maternal low-protein (MLP) diet in rats programs hypertension in offspring.
Purpose of the Study:
- To investigate the intergenerational effects of a maternal low-protein (MLP) diet on blood pressure and nephron number.
- To assess if nutritional insults during gestation can impact multiple generations.
Main Methods:
- Pregnant Wistar rats (F0) received either a control (CON) or MLP diet during gestation.
- Offspring (F1) were mated to produce F2, and F2 to produce F3, without dietary changes.
- Blood pressure and nephron number were measured across generations.
Main Results:
- F1 offspring exposed to MLP diet showed significantly higher systolic blood pressure compared to CON.
- Hypertension and reduced nephron number were observed in the F2 generation, transmitted through both maternal and paternal lines.
- No significant effects were observed in the F3 generation.
Conclusions:
- Fetal protein restriction can program hypertension and impact disease risk in the subsequent generation.
- The study demonstrates transgenerational effects of nutritional insults on cardiovascular health.
- These findings underscore the critical role of maternal nutrition in long-term offspring health outcomes.
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.
