Reproduction Abstracts

Introduction: Preeclampsia is a pregnancy-specific disease characterized by concurrent development of hypertension, proteinuria, and oxidative stress in the placenta. Preeclampsia-like genetic models were also developed by modification of preeclampsia-related genes, such as catechol-O-methyltranferase (COMT).

Materials and methods: In this study, we induced COMT inhibition in mice during pregnancy to reproduce physiological conditions associated with preeclampsia. The expression of gene known as hypoxia biomarker, HIF1α, was highly induced in placenta of this model. The over-expression of HIF1α demonstrates that our experimental conditions closely were similar with preeclampsia. We measured the expression of several calcium transporters (TRPV5, TRPV6, PMCA1, and CaBP-9k) in the placenta, duodenum, and kidney after COMT inhibition on gestation day 17.5 (GD17.5). In addition, we evaluated the calcium transporters in the kidney, duodenum of non-pregnant female mice.

Results and discussion: Placental TRPV5, TRPV6, and PMCA1 expressions were down-regulated by COMT inhibitor (ro41-0960). In addition, the reduced PMCA1 expression in the placenta was reversed by calcium supplementation. Duodenal expressions of TRPV5, TRPV6, and PMCA1 were decreased in the COMT-inhibited mice, and slightly recovered after calcium supplementation. Renal expression of TRPV5, TRPV6, and PMCA1 was also decreased by COMT inhibition, while it was reversed by calcium supplementation to the level of control. Duodenal- and renal calcium transporting genes, TRPV5, TPRV6, PMCA1, and CaBP-9k, were down-regulated by COMT treatment in female mice. Taken together, these results indicate that physiological changes observed in COMT inhibition were showed similar symptom to preeclampsia, which may be related with disturbance of calcium metabolism during pregnancy.