Aberrant Corin and PCSK6 in Placentas of the Maternal Hyperinsulinemia IUGR Rat Model

Objectives: Corin is a protease that converts pro-atrial natriuretic peptide (pro-ANP) to ANP. While the involvement of ANP in the cardiovascular regulation is well established, there is increasing evidence that the pregnant uterus produces ANP, which promotes spiral artery remodeling. The present study examines the alterations in corin and PCSK6, a key enzyme in the conversion of pro-corin to corin, in the placenta of hyperinsulinemic dams (HD) featuring pregnancy-induced hypertension (PIH).

Materials and methods: The study was conducted on female Wistar rats. Rats were rendered hyperinsulinemic by subcutaneous insulin pellet, mated and followed to the twenty-first day of pregnancy. Normal pregnant dams (NPD) served as controls. Both groups were sacrificed on day 21 of gestation and their placentas were dissected along with the mesometrial triangle (MT). The tissue was then sectioned from the maternal surface to the base of the MT, and processed for histological and molecular biology analysis of Corin, PCSK6 and ANP expression/immunoreactivity.

Results: Hyperinsulinemic dams developed PIH, along lower placental and fetal weights. Corin expression and immunoreactivity were significantly decreased in the placenta by ~40-50%, but not in the MT. Similarly, placental but not MT PCSK6 immunoreactivity was lower in HD. Concomitantly with the downregulation of corin/PCSK6, proANP levels increased in the placenta of HD.

Conclusions: Corin and PCSK6 are expressed in the placenta and MT. The decline in these two enzymes in the placenta of HD suggests a role of corin/PCSK6 machinery in the development of PIH and intrauterine growth restriction characterizing hyperinsulinemia.