Fetal Kidney Programming by Maternal Smoking Exposure: Effects on Kidney Structure, Blood Pressure and Urinary Sodium Excretion in Adult Offspring

Abstract

Introduction: Fetal programming by different insults results in low birth weight and reduction in nephron number increasing the risk for adult development of cardiovascular and renal diseases. Maternal smoking is an important modifiable adverse fetal exposure worldwide and leads to a decrease in the offspring's birth weight. Thus far, the specific adverse fetal smoking exposures and mechanisms underlying these associations on renal development and functional disorder are unclear. Methods: The present study investigates, in adult male rats, the effect of smoking exposure (Sk) in uteri on blood pressure (BP) by an indirect tail-cuff method using an electrosphygmomanometer, and its association with nephron structure by stereological estimation, immunohistochemical and histological techniques, in parallel with kidney function creatinine and lithium clearance. Results: The current study showed in a 16-week old Sk offspring enhanced arterial blood pressure associated with, reduced urinary sodium excretion and higher TGF-β1 glomerular expression. Sk glomeruli also presented an upregulated collagen and fibronectin deposition intrinsically related to fibrotic process as compared to age-matched control group. Conclusion: Here, we demonstrate that fetal-programmed Sk offspring present pronounced glomerular TGF-β1 and fibrotic marker expression that may, subsequently, promote a glomerular epithelial-mesenchymal transition activated process in an Sk offspring. Although the precise mechanism responsible for the subsequently renal morphological and functional response in Sk offspring is incompletely known, the current data suggest that changes in renal function are conducive to excess sodium tubule reabsorption that is associated with enhanced TGF-β1, fibronectin and collagen deposition, intrinsically related to fibrotic process, might potentiate the programming of adult hypertension.

Maternal obesity increases the risk of metabolic disease and impacts renal health in offspring

“…Mothers who smoke tobacco during pregnancy can permanently damage their offspring’s kidney health as a result of prematurity and low birth weight [ 64 , 65 ]. This is due to the disruption in delivery of nutrients to the growing fetus that leads to intrauterine growth restriction, which has permanent deleterious effects on renal health in postnatal life [ 66 ]. Though often associated with fetal overgrowth, maternal obesity can also conversely be associated with increased risk of premature birth and low birth weight, with implications for renal development and CKD risk [ 67 ].…”

The Impact of Kidney Development on the Life Course: A Consensus Document for Action

“…These findings were associated with evidence of increased oxidative stress and changes in mitochondrial structure and function in offspring kidneys [350]. Similarly, in rats exposed to maternal smoking, birth weights and nephron numbers were reduced, proinflammatory proteins were upregulated in offspring kidneys, and albuminuria and blood pressure increased over time [111,351]. A prospective cohort study found that exposure to maternal smoking during pregnancy was associated with a dose-dependent reduction in fetal and infant kidney volumes after adjustment for multiple variables, suggesting an independent impact of smoking on fetal kidney development [114,352].…”

Prenatal lead exposure modifies the effect of shorter gestation on increased blood pressure in children

“…Indeed, the Barker hypothesis sprung from the observation that lower birthweight infants were more likely to develop later life hypertension (Barker et al, 1989). While several mechanisms of developmentally programmed hypertension and renal disease have been proposed (Baum, 2010; Block et al, 2015; Schreuder and Nauta, 2007), a consensus document by the Low Birth Weight and Nephron Number working group highlighted “the need to act early to prevent CKD and other related noncommunicable diseases later in life by reducing low birth weight, small for gestational age, prematurity, and low nephron numbers at birth through coordinated interventions” (Low Birth and Nephron Number Working, 2017).…”