Congenital cytomegalovirus infection undermines early development and functions of the human placenta
- PMID: 28477968
- DOI: 10.1016/j.placenta.2017.04.020
Congenital cytomegalovirus infection undermines early development and functions of the human placenta
Abstract
Congenital human cytomegalovirus (HCMV) infection is a major viral cause of birth defects, including microcephaly, neurological deficits, loss of hearing and vision, and intrauterine growth restriction. Despite its public health significance, there is no approved treatment for congenital infection during pregnancy; existing antivirals have unacceptable toxicities. The mechanisms of HCMV-induced placental injury, reduced capacity for compensatory development and transmission to the fetus are poorly understood, limiting the development of alternative strategies for clinical management of the disease. Recently, self-renewing, multipotent trophoblast progenitor cells (TBPCs) were reported to reside in the chorion of the human placenta and differentiate into the mature trophoblast subtypes - transport syncytiotrophoblasts and invasive cytotrophoblasts - forming chorionic villi, the functional units of the placenta. HCMV infects TBPCs, reducing the population of progenitor cells and their functional capacity to self-renew, migrate and differentiate. Human TBPCs and chorionic villus explants from first trimester represent relevant models for evaluating efficacies of new antiviral agents in protecting and restoring growth of the developing placenta in response to adverse conditions. Correlating pathology from complications of congenital HCMV infection with impaired development in the tissue environment of anchoring villus explants and defects in TBPC differentiation may enable identification of molecular pathways that could serve as targets for intervention. Here we summarize studies that could open up novel avenues of research on potential therapeutics to sustain placental development, promote differentiation and improve function and pregnancy outcomes.
Keywords: Congenital infection; Cytotrophoblasts; Syncytiotrophoblasts; Trophoblast progenitor cells.
Copyright © 2017. Published by Elsevier Ltd.
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