Novakovic Predrag, Harding John C S, Al-Dissi Ahmad N, Detmer Susan E
Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
PLoS One. 2017 Mar 2;12(3):e0173360. doi: 10.1371/journal.pone.0173360. eCollection 2017.
The pathogenesis of fetal death associated with porcine reproductive and respiratory syndrome (PRRS) is hypothesized to be a consequence of PRRS virus-induced apoptosis at the maternal-fetal interface (MFI). The objectives of this study were to evaluate distribution and degree of apoptosis in the uterine and fetal placental tissues during the experimental type 2 PRRS virus (PRRSV) infection and determine associations between apoptosis at the MFI, PRRSV RNA concentration and antigen staining intensity, PRRSV-induced microscopic lesions, and fetal preservation status. A total of 114 naïve, high-health pregnant gilts were inoculated with type 2 PRRSV on gestation day 85±1 with euthanasia 21 days later; 19 sham-inoculated gilts served as controls. Two hundred and fifty samples of uterine tissue with fetal placenta were selected based on negative, low PRRSV RNA, and high PRRSV RNA concentration (0, < or > 2.7 log10 copies/mg, respectively). TUNEL assay was used to detect apoptosis in the endometrium and at the MFI. PRRSV RNA concentration and numbers of PRRSV immunopositive cells in uterine and placental tissue were positively associated with the severity of apoptosis in the endometrium and the MFI (P<0.001, P<0.05 and P<0.001, respectively). The number of TUNEL positive cells at the MFI was also positively associated with the severity (P<0.001) of vasculitis, but not total numbers of inflammatory cells in the endometrium. Increased numbers of TUNEL positive cells at the MFI were associated with PRRSV load in the fetal thymus, and greater odds of meconium staining of the fetus at 21 days post infection (P<0.001 for both). These findings suggest an important role of apoptosis in the pathogenesis of uterine epithelial and trophoblastic cell death at the MFI. Moreover, apoptosis at the MFI is significantly associated with fetal demise during in utero type 2 PRRSV infection.
与猪繁殖与呼吸综合征（PRRS）相关的胎儿死亡发病机制被推测为是PRRS病毒诱导母胎界面（MFI）细胞凋亡的结果。本研究的目的是评估实验性2型PRRS病毒（PRRSV）感染期间子宫和胎儿胎盘组织中细胞凋亡的分布和程度，并确定MFI处的细胞凋亡、PRRSV RNA浓度和抗原染色强度、PRRSV诱导的微观病变以及胎儿存活状态之间的关联。总共114头未接触过病原体的高健康状态怀孕母猪在妊娠第85±1天接种2型PRRSV，21天后实施安乐死；19头假接种母猪作为对照。根据PRRSV RNA浓度阴性、低浓度和高浓度（分别为0、<或>2.7 log10拷贝/毫克），选取250份带有胎儿胎盘的子宫组织样本。采用TUNEL法检测子宫内膜和MFI处的细胞凋亡。子宫和胎盘组织中PRRSV RNA浓度及PRRSV免疫阳性细胞数量与子宫内膜和MFI处细胞凋亡的严重程度呈正相关（分别为P<0.001、P<0.05和P<0.001）。MFI处TUNEL阳性细胞数量也与血管炎的严重程度呈正相关（P<0.001），但与子宫内膜中炎症细胞总数无关。MFI处TUNEL阳性细胞数量增加与胎儿胸腺中的PRRSV载量相关，且与感染后21天胎儿胎粪染色的几率增加相关（两者均为P<0.001）。这些发现表明细胞凋亡在MFI处子宫上皮细胞和滋养层细胞死亡的发病机制中起重要作用。此外，在子宫内2型PRRSV感染期间，MFI处的细胞凋亡与胎儿死亡显著相关。
