Maternal nutrient restriction alters renal development and blood pressure regulation of the offspring
Kathryn A Brennan1, David M Olson, Michael E Symonds
1Perinatal Research Centre, Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Canada. mgxkb@nottingham.ac.uk
Insights
Maternal nutrient restriction during pregnancy can impact fetal kidney development and programming of adult blood pressure. This study investigated how nutrient restriction affects growth factors and prostaglandins, crucial for kidney function.
Area of Science:
- Developmental biology
- Nutritional science
- Cardiovascular physiology
Background:
- The in utero environment influences adult hypertension risk.
- Hypertension is linked to impaired kidney function and organogenesis.
- Prostaglandins (PG) and growth factors are vital for kidney development and function.
Purpose of the Study:
- To investigate the long-term effects of maternal nutrient restriction (NR) on kidney development and adult blood pressure.
- To explore the relationship between maternal NR and compromised renal development.
- To examine the impact of NR on renal prostaglandin and growth factor status.
Main Methods:
- Utilized sheep models for fetal renal development under 50% NR during gestation.
- Employed rat models for postnatal kidney development and adult function with 50% NR throughout pregnancy.
- Conducted molecular analysis of fetal sheep and adult rat kidneys.
Main Results:
- Maternal NR affected the growth hormone-insulin-like growth factor (GH-IGF) axis in fetal sheep kidneys, with timing and singleton/twin status being critical factors.
- Nutritional differences in PG receptors and synthesis/degradation enzymes were observed in rat kidneys, persisting into adulthood.
- NR impacts GH-IGF and PG axes, potentially programming renal function and adult blood pressure.
Conclusions:
- Maternal nutrient restriction significantly alters fetal kidney development and the expression of key molecular pathways.
- These alterations in the GH-IGF and PG axes are implicated in the nutritional programming of renal function and hypertension risk.
- The study highlights the critical role of maternal nutrition in long-term offspring health outcomes, particularly cardiovascular and renal health.
Abstract:
Studies have shown that the risk of hypertension in adulthood can be affected by the in utero environment. It is established that hypertension is linked to compromised kidney function and that factors affecting organogenesis can increase the risk of later disease. Prostaglandins (PG) and growth factors are known to play an important role in regulating kidney function and renal organogenesis. The extent, however, to which global energy restriction (where all nutrients are reduced) of the mother can programme later blood pressure control or renal PG and growth factor status is unknown. A study is described that aimed to examine the long-term effects of maternal nutrient restriction (NR) and elucidate their relationship with compromised kidney development. First, it was necessary to establish animal models. A sheep model of 50% NR during specific stages of gestation was used to investigate fetal renal development, whilst a rat model of 50% NR throughout pregnancy was used to investigate postnatal kidney development and adult functioning. Molecular analysis has shown that expression of the growth hormone-insulin-like growth factor (GH-IGF) axis is affected by NR in the fetal sheep kidneys, and that changes are dependent on the timing of NR and whether the fetus is a singleton or a twin. Analysis of the kidneys from the rat model has shown nutritional differences in the expression of PG receptors and the enzymes responsible for PG synthesis and degradation that persist into adulthood. In conclusion, NR does affect the GH-IGF and PG axes, and these changes may be important in the nutritional programming of renal functioning and adult blood pressure control.
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