Abnormal angiogenesis of placenta in progranulin-deficient mice

Progranulin (PGRN) is a secreted growth factor involved in pleiotropic functions, particularly angiogenesis. A distinctly different placental expression of PGRN has been reported between normal pregnancies and pregnancies with complications, such as pre-eclampsia or fetal growth restriction. However, the role of PGRN in placental vascular development remains to be elucidated. In the present study, PGRN-knockout mice (PGRN(−/−)) were used to investigate the role of PGRN in the development of placental blood vessels and placental formation. Placental weights and pup body weights were significantly lower in the PGRN(−/−) mice compared with the wild-type mice. Reduced labyrinthine layer areas and aberrant vascularization were also observed via hematoxylin and eosin staining of PGRN(−/−) mice at embryonic day 14.5 (E14.5) and E17.5. In addition, the morphological data obtained via immunohistochemistry, immunofluorescence staining and western blotting demonstrated decreased expression levels of the blood vessel markers α-smooth muscle actin and CD31 in PGRN(−/−) placentas. Furthermore, vasodilator endothelial nitric oxide synthase was reduced in the PGRN(−/−) placenta. These results indicated that PGRN serves an essential role in the normal angiogenesis of the placental labyrinth in mice.