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.