The investigation of calpain in human placenta with fetal growth restriction.

PROBLEM: The mechanism of fetal growth restriction (FGR) is not fully understood. In this study, we explored the contribution of the calpain-calpastatin system and the activated states of calpains in human FGR placenta.

METHOD OF STUDY: The placentas were collected from patients of FGR (n = 17) and controls (n = 23) at elective cesarean sections in Nagoya City University Hospital and used for experiments upon informed consent. The existence and the expression of calpains and calpastatin in human placenta were compared between FGR and controls using immunohistochemistry, SDS-PAGE, and Western blotting.

RESULTS

Staining of calpains (pre-, post-μ-calpain, pre-, post-m-calpain, and calpain-6) and calpastatin was observed in cytoplasm of trophoblast cells, both in FGR and control placenta. Pre-μ-calpain was located in the cytoplasm, and post-μ-calpain was located mainly in proximity to the cytoplasmic membrane. The expression of pre-μ-calpain was significantly higher (P < .001) and calpain-6 was significantly lower (P = .01) in FGR placentas. The inactive μ-calpain (80 kDa) was significantly elevated (P < .01), and active μ-calpain (76 kDa) was significantly decreased (P = .01) in FGR placentas.

CONCLUSION

The results demonstrate that activation of μ-calpain is suppressed in FGR placentas and that calpain-6 in human placenta is involved in the pathology of FGR.