PrP-C and PrP-Sc at the fetal-maternal interface

Scrapie is a naturally occurring prion (PrP) disease causing a fatal neurod egenerative disorder in sheep and goats. Previous studies suggest that scra pie is transmitted naturally through exposure to the scrapie agent in waste d placentas of infected ewes, This study determined the distribution and bi ochemical properties of PrP cellular (PrP-C) and the distribution of PrP sc rapie (PrP-Sc) in reproductive, placental, and selected fetal tissues and f etal fluids in sheep. Glycosylated, N-terminally truncated, proteinase K-se nsitive PrP-C with apparent molecular masses of 23-37 kDa was present in re productive, placental, and fetal tissues and fetal fluids. PrP-C was low or undetectable in intercotyledonary chorioallantois, amnion, urachus, amniot ic fluid, and fetal urine. In pregnant ewes, cotyledonary chorioallantois, allantoic fluid, and caruncular endometrium contained higher levels of PrP- C than did intercaruncular endometrium, myometrium, oviduct, ovary, fetal b ladder, or fetal kidney, Caruncular endometrial PrP-C was up-regulated duri ng pregnancy, Despite the wide distribution of PrP-C in reproductive, place ntal, and selected fetal tissues and fetal fluid, PrP-Sc was detected only in caruncular endometrium and cotyledonary chorioallantois of pregnant scra pie-infected ewes, The embryo/fetus may not be exposed to scrapie in utero because it is separated physically from PrP-positive allantois and chorioal lantois by PrP-negative amnion.