|Knowles, Donald - Don|
Submitted to: Proceedings of the National Academy of Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/25/2002
Publication Date: 4/30/2002
Citation: Tuo, W., O'Rourke, K.I., Zhuang, D., Cheevers, W., Spraker, T., Knowles, Jr., D.P. 2002. Pregnancy status and fetal prion genetics determine PrPSc accumulation in placentomes of scrapie infected sheep. Proceedings of the National Academy of Sciences. 99(9):6310-6315. Interpretive Summary: Scrapie is a fatal neurodegenerative disease in sheep and goats. This study determined the effects of fetal genetics and reproductive status on PrPSc accumulation in the placentome of scrapie-infected sheep. We showed that placentomal PrPSc accumulation was detected only in 171 QQ ewes pregnant with 171QQ fetuses, but not with 171QR fetuses. PrPSc accumulation was not detected in the non-pregnant uterus of scrapie-infected sheep. The results suggest that scrapie infected ewes will not shed scrapie agent through reproductive and/or placental tissues if they are not pregnant or pregnant with a genetically resistant fetus.
Technical Abstract: Ovine scrapie is a fatal neurodegenerative disorder, which may be transmitted through exposure to infected uterine and placental tissues. Susceptibility to scrapie in sheep is primarily controlled by polymorphisms in the PrP gene. Scrapie in U. S. Suffolk sheep 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. This study demonstrated that accumulation of PrPSc in uterine-placental epithelial cells in the placentome was determined by foetal genotype and reproductive status of scrapie-infected ewes. PrPSc 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 PrPSc plaques in placentomes was temporally associated with stage of gestation. There was a tendency toward increased size and number of placentomal PrPSc plaques from the endometrial stalk (maternal side) to chorionic plate (foetal side). These results indicate that accumulation of PrPSc is eliminated or reduced to undetectable levels in reproductive tissues if infected ewes are not pregnant or conceive conceptuses with a resistant genotype.