Received August 7, 2007
Accepted on January 10, 2008

BASIC RESEARCH

Maternal Diabetes Modulates Renal Morphogenesis in Offspring

Stella Tran ^*, Yun-Wen Chen ^*, Isabelle Chenier ^*, John S.D. Chan ^*, Susan Quaggin , Marie-Josée Hébert ^*, Julie R. Ingelfinger , and Shao-Ling Zhang ^*1

*University of Montreal, Centre Hospitalier de l’Université de Montréal–Hôtel-Dieu, Research Centre, Montreal, Quebec, Canada; Samuel Lunenfeld Research Institute, University of Toronto, Toronto, Ontario, Canada; and Pediatric Nephrology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

¹ To whom correspondence should be addressed. E-mail: shao.ling.zhang{at}umontreal.ca.

	Abstract

Maternal diabetes leads to an adverse in utero environment, but whether maternal diabetes impairs nephrogenesis is unknown. Diabetes was induced with streptozotocin in pregnant Hoxb7–green fluorescence protein mice at embryonic day 13, and the offspring were examined at several time points after birth. Compared with offspring of nondiabetic controls, offspring of diabetic mice had lower body weight, body size, kidney weight, and nephron number. The observed renal dysmorphogenesis may be the result of increased apoptosis, because immunohistochemical analysis revealed significantly more apoptotic podocytes as well as increased active caspase-3 immunostaining in the renal tubules compared with control mice. Regarding potential mediators of these differences, offspring of diabetic mice had increased expression of intrarenal angiotensinogen and renin mRNA, upregulation of NF-B isoforms p50 and p65, and activation of the NF-B pathway. In conclusion, maternal diabetes impairs nephrogenesis, possibly via enhanced intrarenal activation of the renin-angiotensin system and NF-B signaling.