University of Saskatchewan, Saskatoon, SK, Canada.
Purdue University, West Lafayette, IN.
Vet Pathol. 2022 Nov;59(6):940-949. doi: 10.1177/03009858221105053. Epub 2022 Jun 20.
Angiogenesis and cell proliferation in reproductive tissues are essential events for the maintenance of pregnancy, and alterations can lead to compromised fetal development and survival. Porcine reproductive and respiratory syndrome virus 2 (PRRSV-2) induces reproductive disease with negative financial and production impact on the swine industry. PRRSV-2 infection alters placental physiology through inflammatory and apoptotic pathways, yet fetal susceptibility varies. This study aimed to evaluate angiogenesis and cell proliferation in the porcine maternal-fetal interface (MFI) and determine if these physiological processes were altered by PRRSV-2 infection. Thirty-one pregnant gilts were inoculated with PRRSV-2 at gestation day 86 ± 0.4 (mean ± SD). Seven control gilts were sham-inoculated. All gilts were euthanized at 12 days postinoculation. Angiogenesis and cell proliferation were determined through the detection of vascular endothelial growth factor (VEGF) and Ki-67, respectively, using immunofluorescence of the MFI from 4 fetal resilience groups: uninfected (UNIF), high viral load-viable (HVL-VIA), and HVL-meconium-stained (MEC) from PRRSV-infected gilts, as well from sham-inoculated (CON) gilts. VEGF immunolabeling in the uterine submucosa was significantly lower in MEC compared with UNIF and HVL-VIA groups. Significantly greater Ki67 immunolabeling was detected in the trophoblasts of CON fetuses versus all other groups, and in uterine epithelium of CON and UNIF fetuses versus HVL-VIA and MEC. These results suggest that fetal resilience may be related to greater cell proliferation in uterine epithelium, and fetal compromise with reduced uterine submucosal angiogenesis, except fetuses with intrauterine growth restriction, in which inherently lower submucosal angiogenesis may be protective against PRRSV infection.
生殖组织中的血管生成和细胞增殖对于维持妊娠至关重要，而这些过程的改变可能导致胎儿发育和生存受损。猪繁殖与呼吸综合征病毒 2（PRRSV-2）通过炎症和细胞凋亡途径引起生殖疾病，对养猪业造成负面的经济和生产影响。PRRSV-2 感染通过炎症和细胞凋亡途径改变胎盘生理学，但胎儿的易感性不同。本研究旨在评估猪母体-胎儿界面（MFI）中的血管生成和细胞增殖，并确定这些生理过程是否因 PRRSV-2 感染而改变。31 头妊娠母猪在妊娠 86±0.4 天（均值±标准差）接种 PRRSV-2。7 头对照母猪假接种。所有母猪在接种后 12 天安乐死。通过免疫荧光法检测血管内皮生长因子（VEGF）和 Ki-67 分别评估血管生成和细胞增殖，MFI 来自于 4 个胎儿耐受组：未感染（UNIF）、高病毒载量-存活（HVL-VIA）和 PRRSV 感染母猪的胎粪污染（MEC），以及假接种（CON）母猪。与 UNIF 和 HVL-VIA 组相比，MEC 组子宫黏膜下的 VEGF 免疫标记明显降低。与所有其他组相比，CON 胎儿的滋养层中 Ki67 免疫标记明显增加，而 CON 和 UNIF 胎儿的子宫上皮中 Ki67 免疫标记明显增加与 HVL-VIA 和 MEC 相比。这些结果表明，胎儿耐受可能与子宫上皮中更高的细胞增殖有关，而胎儿受损与子宫黏膜下血管生成减少有关，但对于宫内生长受限的胎儿除外，其内在较低的黏膜下血管生成可能对 PRRSV 感染具有保护作用。
