Adverse prenatal environment and kidney development: implications for programing of adult disease

Abstract

The 'developmental origins of health and disease' hypothesis suggests that many adult-onset diseases can be attributed to altered growth and development during early life. Perturbations during gestation can be detrimental and lead to an increased risk of developing renal, cardiovascular, metabolic, and neurocognitive dysfunction in adulthood. The kidney has emerged as being especially vulnerable to insult at almost any stage of development resulting in a reduction in nephron endowment. In both humans and animal models, a reduction in nephron endowment is strongly associated with an increased risk of hypertension. The focus of this review is twofold: i) to determine the importance of specific periods during development on long-term programing and ii) to examine the effects of maternal perturbations on the developing kidney and how this may program adult-onset disease. Recent evidence has suggested that insults occurring around the time of conception also have the capacity to influence long-term health. Although epigenetic mechanisms are implicated in mediating these outcomes, it is unclear as to how these may impact on kidney development. This presents exciting new challenges and areas for research.Reproduction (2014) 147 R189-R198

Improving our resolution of kidney morphogenesis across time and space

“…Evidence for long term effects on renal structure and hence function as a result of gestational insult (fetal programming) is well established in the mouse [47 ], with hypoxia [48 ], elevated glucocorticoids [47 ] and diabetes [49 ] all shown to reduce nephron number and alter renal function and blood pressure. Translation of these observations into the human setting is difficult to predict given the substantially different approach to kidney organogenesis seen between mouse and man.…”

Counting glomeruli and podocytes

“…At about the same time, David Barker and his colleagues proposed the fetal origins hypothesis of adult disease, now known as the developmental origins of health and disease (DOHaD) hypothesis, which originally postulated that suboptimal events during prenatal development increase the risk of cardiovascular disease in adulthood. The range of adult chronic diseases linked to fetal and early postnatal origins has now expanded to include cardiovascular disease [3, 4], renal disease [5, 6], obesity [7, 8] and diabetes [9, 10]. …”

Salt-Sensitive Hypertension

“…Relatively mild maternal protein deficiency leads to abnormal nephron structure and dysregulation of the renin-angiotensin II-aldosterone system (RAAS) 2, 3 . The report in this issue, “ Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in Dahl Salt-Sensitive Rats ” by Geurts et al 4 builds upon the finding that a protein-sufficient casein-based diet significantly increases the degree of salt-induced hypertension and renal damage in inbred Dahl Salt-Sensitive rat strains SS/Mcw compared to SS/Crl fed a grain-based diet with similar proportions of protein, fat and carbohydrates 5 .…”