title: Pregnancy status and fetal prion genetics determine PrPSc accumulation in placentomes of scrapie-infected sheep.
abstract: Ovine scrapie is a fatal neurodegenerative disorder that may be transmitted through exposure to infected uterine and placental tissues. Susceptibility to scrapie is primarily controlled by polymorphisms in the prion protein (PrP) gene. Scrapie in the U.S. Suffolk breed and in many breeds in Europe 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. This study demonstrated that accumulation of PrP(Sc) in uterine-placental epithelial cells in the placentome was determined by fetal PrP genotype and the pregnancy status of scrapie-infected ewes. PrP(Sc) was detected in 171QQ placentomes of infected ewes, but not in placentomes of infected ewes pregnant with 171QR conceptuses or in the non-pregnant uterus of infected ewes. The distribution of PrP(Sc) plaques in placentomes was temporally associated with stage of gestation. There was a tendency toward increased size and number of placentomal PrP(Sc) plaques from the endometrial stalk (maternal side) to chorionic plate (fetal side). These results indicate that accumulation of PrP(Sc) is eliminated or reduced to undetectable levels in reproductive and placental tissues if infected ewes are not pregnant or conceive conceptuses with a resistant PrP genotype.
authors.affiliation: Animal Disease Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Pullman, WA 99164, USA. wtuo@vetmed.wsu.edu
authors.forename: Wenbin
authors.initials: W
authors.lastname: Tuo
authors.forename: Katherine I
authors.initials: KI
authors.lastname: O'Rourke
authors.forename: Dongyue
authors.initials: D
authors.lastname: Zhuang
authors.forename: William P
authors.initials: WP
authors.lastname: Cheevers
authors.forename: Terry R
authors.initials: TR
authors.lastname: Spraker
authors.forename: Donald P
authors.initials: DP
authors.lastname: Knowles
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004717:Endometrium / Q000378:metabolism; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D007150:Immunohistochemistry; D010920:Placenta / Q000378:metabolism*; D018620:PrPSc Proteins / Q000096:biosynthesis* / Q000235:genetics*; D011247:Pregnancy; D011270:Pregnancy, Animal; D012608:Scrapie / Q000378:metabolism*; D012756:Sheep; D013997:Time Factors
chemical_list: D018620:PrPSc Proteins