Microbial Vertical Transmission during Human Pregnancy

Abstract

Congenital infections with pathogens such as Zika virus, Toxoplasma gondii, Listeria monocytogenes, Treponema pallidium, parvovirus, HIV, varicella zoster virus, Rubella, Cytomegalovirus, and Herpesviruses are a major cause of morbidity and mortality worldwide. Despite the devastating impact of microbial infections on the developing fetus, relatively little is known about how pathogens associated with congenital disease breach the placental barrier to transit vertically during human pregnancy. In this Review, we focus on transplacental transmission of pathogens during human gestation. We introduce the structure of the human placenta and describe the innate mechanisms by which the placenta restricts microbial access to the intrauterine compartment. Based on current knowledge, we also discuss the potential pathways employed by microorganisms to overcome the placental barrier and prospects for the future.

Keywords: Cytomegalovirus; Listeria monocytogenes; Toxoplasma gondii; Zika virus; placenta; trophoblast; vertical transmission.

Figure 1. Structure and cellular composition of the human placenta

(A) Schematic of the uterine cavity during pregnancy. The developing fetus is encased within the amniotic cavity, surrounded by the chorion and amnion, and anchored to the maternal decidua by the placenta (at the site of attachment, the decidua basalis). (B) Maternal blood fills the intervillous space (IVS) via spiral arteries that bathe the surfaces of the placenta in maternal blood (once the maternal microvasculature has been established). (C) The human hemochorial placenta is formed by villous trees composed of both floating villi and anchoring villi, which attach directly to the decidua basalis by the invasion of extravillous trophoblasts (EVTs). The human placenta villous trees are covered by syncytiotrophoblasts, with a layer of cytotrophoblasts (which become discontinuous throughout pregnancy) below this layer. Several pathogens, including Listeria monocytogenes (L. mono), Toxoplasma gondii (T. gondii), human CMV (HCMV), and Zika virus (ZIKV), are thought to access the villous core following replication in EVTs. (D) Left, differential interference contrast (DIC) image of a floating villous from an ~ 20-week gestation placenta highlighting the syncytiotrophoblast (SYN) layer and underlying fetal microvasculature (MV). Right, confocal micrograph of cytokeratin-19-positive SYNs and the underlying cytokeratin-19-negative core of the villous trees. Scale bar, 50 μm.