Submitted to: Journal of Reproductive Immunology
Publication Type: Abstract Only
Publication Acceptance Date: March 1, 2004
Publication Date: June 3, 2004
Citation: Tuo, W. 2004. Prion transport across the placenta.. Journal of Reproductive Immunology 51, p. 408.
Scrapie is a prion disease causing a fatal neurodegenerative disorder in sheep and goats. Our studies determined the distribution and properties of PrP-C and PrP-Sc in ovine reproductive, placental, and fetal tissues/fluids. Glycosylated, N-terminally truncated, PK-sensitive PrP-C with apparent molecular masses of 23-37 kDa was present. Cotyledonary chorioallantois, allantoic fluid, and caruncular endometrium contained higher levels of PrP-C than did intercaruncular endometrium, myometrium, oviduct, ovary, fetal bladder, or kidney in pregnant sheep. Caruncular endometrial PrP-C was up-regulated during pregnancy. Despite the wide distribution of PrP-C, PrP-Sc was detected only in caruncular endometrium and cotyledonary chorioallantois of pregnant infected ewes. In utero transmission of scrapie is unlikely because embryo/fetus is separated by PrP- amnion from PrP+ chorioallantois. Furthermore, scrapie occurs in sheep homozygous for glutamine (171QQ), but rarely in sheep heterozygous for glutamine and arginine (171QR) or homozygous for arginine (171RR) at codon 171 of the PrP gene. Accumulation of PrP-Sc in placentome was determined by fetal PrP genotype and pregnancy. PrP-Sc was detected in 171QQ placentomes of infected ewes, but not in placentomes with 171QR conceptuses or in non-pregnant uterus of infected ewes. The distribution of placentomal PrP-Sc was temporally associated with gestational stage. There was a tendency toward increased size and number of PrP-Sc plaques from the maternal to fetal side. The results indicate that PrP-Sc accumulation is eliminated or reduced to undetectable levels in reproductive tissues if infected ewes were not pregnant or conceive conceptuses with a resistant PrP genotype.