Maternal exposure to di-(2-ethylhexyl)phthalate alters kidney development through the renin-angiotensin system in offspring

Abstract

Di-(2-ethylhexyl)phthalate (DEHP) is a widely used industrial plasticizer to which humans are widely exposed. We investigated the consequences of maternal exposure to DEHP on nephron formation, examined the programming of renal function and blood pressure and explored the mechanism in offspring. Maternal rats were treated with vehicle, 0.25 and 6.25mg/kg body weight/day DEHP respectively from gestation day 0 to postnatal day 21. Maternal DEHP exposure resulted in lower number of nephrons, higher glomerular volume and smaller Bowman's capsule in the DEHP-treated offspring at weaning, as well as glomerulosclerosis, interstitial fibrosis and effacement of podocyte foot processes in adulthood. In the DEHP-treated offspring, the renal function was lower and the blood pressure was higher. The renal protein expression of renin and angiotensin II was reduced at birth day and increased at weaning. Maternal DEHP exposure also led to reduced mRNA expression of some renal development involved genes at birth day, including Foxd1, Gdnf, Pax2 and Wnt11. While, the mRNA expression of some genes was raised, including Bmp4, Cdh11, Calm1 and Ywhab. These data show that maternal DEHP exposure impairs the offspring renal development, resulting in a nephron deficit, and subsequently elevated blood pressure later in life. Our findings suggest that DEHP exposure in developmental periods may affect the development of nephrons and adult renal disease through inhibition of the renin-angiotensin system.