Analysis of fetal microchimeric levels in congenital Zika virus syndrome
fetal microchimerism; congenital zika virus syndrome; maternal immune response;
In 2015, Brazil faced a severe Zika virus (ZIKV) epidemic transmitted by Aedes aegypti mosquitoes, causing febrile illness. It prompted a study to detect ZIKV in the amniotic fluid of pregnant women with microcephalic babies, confirming its association with CNS malformations. During pregnancy, the maternal immune system adjusts to tolerate embryo cells carrying paternal genetic material, while maternal antibodies provide passive immunity. However, congenital Zika disrupts this immune balance, potentially leading to brain malformations. Our research investigates the origin of these malformations, exploring microchimerism, where cells from one individual enter another during pregnancy. We aim to shed light on the underlying mechanisms of Zika-related complications. Here, we performed an intrauterine surgery to expose the embryos and inoculate saline, inactivated ZIKV (inZIKV), and ZIKV into the amniotic fluid, analyzing after five days. We measured the levels of fetal cells in the maternal blood and three regions of the maternal brain: Olfactory bulb (OB), hippocampus (HC), and cerebellum (CRB). Furthermore, we evaluated microchimerism between siblings, comparing the embryo's brain and liver as the potential harboring sites for the microchimeric cells. Our results revealed no significant difference in the levels of exchanged fetal cells between the control groups (saline and inZIKV) and those inoculated with ZIKV, both in the maternal blood and brain regions. However, there was a notable difference in cell transfer between siblings, particularly in the brain, when comparing the Zika virus group with the saline and inZIKV groups. We conclude that the ZIKV increases the levels of microchimeric cells exchanged between siblings, indicating a disruption in the permeability of the placental and blood-brain barriers. This finding implies that a potential leakage of embryonic cells to the mother could enhance the likelihood of disrupting maternal tolerance mechanisms.