Koi H, Zhang J, Makrigiannakis A, Getsios S, MacCalman C D, Kopf G S, Strauss J F, Parry S
Center for Research on Reproduction and Women's Health, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Biol Reprod. 2001 Mar;64(3):1001-9. doi: 10.1095/biolreprod64.3.1001.
The molecular mechanisms and pathologic significance of placental viral infections are poorly understood. We investigated factors that regulate placental infection by adenovirus, which is the most common viral pathogen identified in fetal samples from abnormal pregnancies (i.e., fetal growth restriction, oligohydramnios, and nonimmune fetal hydrops). We also determined the pathologic significance of placental adenovirus infection. Northern hybridization, flow cytometry, and immunostaining revealed that placental expression of the coxsackievirus and adenovirus receptor (CAR) varied with gestational age and trophoblast phenotype. The CAR was continuously expressed in invasive or extravillous trophoblast cells but not in villous trophoblast cells. We postulate that the villous syncytiotrophoblast, which does not express CAR and is resistant to adenovirus infection, limits the transplacental transmission of viral pathogens, including adenovirus. Conversely, extravillous trophoblast cells underwent apoptosis when infected by adenovirus in the presence of decidual lymphocytes (which simulated the maternal immune response to viral infection). Thus, adenovirus infection and/or the maternal immune response to adenovirus infection induced the death of placental cell types that expressed CAR. Consequently, we speculate that adenovirus infection of extra-villous trophoblast cells may negatively impact the process of placental invasion and predispose the mother and fetus to adverse reproductive outcomes that result from placental dysfunction.
胎盘病毒感染的分子机制和病理意义目前尚不清楚。我们研究了调节腺病毒感染胎盘的因素，腺病毒是在异常妊娠（即胎儿生长受限、羊水过少和非免疫性胎儿水肿）的胎儿样本中鉴定出的最常见病毒病原体。我们还确定了胎盘腺病毒感染的病理意义。Northern杂交、流式细胞术和免疫染色显示，柯萨奇病毒和腺病毒受体（CAR）在胎盘中的表达随孕周和滋养层细胞表型而变化。CAR在侵袭性或绒毛外滋养层细胞中持续表达，但在绒毛滋养层细胞中不表达。我们推测，不表达CAR且对腺病毒感染具有抗性的绒毛合体滋养层细胞限制了包括腺病毒在内的病毒病原体的经胎盘传播。相反，在蜕膜淋巴细胞存在的情况下（模拟母体对病毒感染的免疫反应），当绒毛外滋养层细胞被腺病毒感染时会发生凋亡。因此，腺病毒感染和/或母体对腺病毒感染的免疫反应诱导了表达CAR的胎盘细胞类型的死亡。因此，我们推测绒毛外滋养层细胞的腺病毒感染可能对胎盘侵袭过程产生负面影响，并使母亲和胎儿易患因胎盘功能障碍导致的不良生殖结局。
