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Structural and functional changes in the kidney caused by adverse fetal and neonatal environments

Journal

MOLECULAR BIOLOGY REPORTS
Volume 49, Issue 3, Pages 2335-2344

Publisher

SPRINGER
DOI: 10.1007/s11033-021-06967-w

Keywords

Low birth weight; Intrauterine growth restriction; Nephron number; Capillary rarefaction; Prematurity; Epigenetics

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The early developmental environment affects health and disease risk in adulthood, particularly in relation to the structure and function of the kidneys. Low birth weight and preterm birth can result in structural changes in the kidneys, with low nephron number being a main alteration.
Health and disease risk in the adulthood are known to be affected by the early developmental environment. Kidney diseases are one of these diseases, and kidneys are altered both structurally and functionally by adverse pre- and perinatal events. The most known structural change is low nephron number seen in subjects born low birth weight and/or preterm. In various animal models of intrauterine growth restriction (IUGR), one of the causes of low birth weight, the mechanism of low nephron number was investigated. While apoptosis of metanephric mesenchyme has been suggested to be the cause, I showed that suppression of ureteric branching, global DNA methylation, and caspase-3 activity also contributes to the mechanism. Other structural changes caused by adverse fetal and neonatal environments include peritubular and glomerular capillary rarefaction and low podocyte endowment. These are aggravated by postnatal development of focal glomerulosclerosis and tubulointerstitial fibrosis that result from low nephron number. Functional changes can be seen in tubules, endothelium, renin-angiotensin system, sympathetic nervous system, oxidative stress, and others. As an example, I reported that aggravated nitrosative stress in a rat IUGR model resulted in more severe tubular necrosis and tubulointerstitial fibrosis after unilateral ureteral obstruction. The mechanism of various functional changes needs to be clarified but may be explained by epigenetic modifications.

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