Placental infection with human papillomavirus is associated with spontaneous preterm delivery

Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, 2000 Courtyard Building, 3400 Spruce Street, Philadelphia, PA 19104, USA.
Human Reproduction (Impact Factor: 4.57). 03/2008; 23(3):709-15. DOI: 10.1093/humrep/dem404
Source: PubMed


We sought to determine if human papillomavirus (HPV) infection of extravillous trophoblast cells reduces cell invasion and if placental infection is associated with adverse reproductive outcomes attributed to placental dysfunction.
We conducted apoptosis and invasion assays using extravillous trophoblast (HTR-8/SVneo) cells that were transfected with a plasmid (pAT-HPV-16) containing the entire HPV-16 genome. In order to associate HPV infection with reproductive outcomes, we conducted a case-control study to detect HPV DNA in the extravillous trophoblast region of placentas from cases of spontaneous preterm delivery, severe pre-eclampsia requiring delivery at <37 weeks and controls who delivered at term.
Rates of apoptosis were 3- to 6-fold greater in transfected cells than in non-transfected cells or cells transfected with an empty plasmid. Invasion of transfected cells through extracellular matrices was 25-58% lower than that of the controls. HPV was detected more frequently in placentas from spontaneous preterm deliveries than in placentas from controls (P = 0.03). Identification of HPV in placentas from cases of pre-eclampsia was not significantly different to controls.
HPV infection of extravillous trophoblast induces cell death and may reduce placental invasion into the uterine wall. Thus, HPV infection may cause placental dysfunction and is associated with adverse pregnancy outcomes, including spontaneous preterm delivery.

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Available from: Deborah B Nelson, Feb 13, 2014
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    • "HPV infection rates in spontaneous abortions of the first and second trimesters have been reported to be in the 50– 70% range [2] [3]. The presence of HPV has been detected in the placentas derived from spontaneous abortions and preterm deliveries cases [2]. The origin of the HPV found in the placental cells was postulated to be circulating cellfree HPV DNA in the blood. "
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    • "Migration and invasion of extravillous trophoblast into the spiral arteries are critical events during placentation (Brosens et al., 1967; Pijnenborg et al., 1983). It has been suggested that inflammation within the gestational compartment may lead to impaired trophoblast cellular function, contributing to the placental dysfunction seen in pregnancyrelated disorders (Anton et al., 2012) such as IUGR, preeclampsia and preterm birth (Germain et al., 1999; Gomez et al., 2008; Kim et al., 2002; Ness and Sibai, 2006; Riewe et al., 2010). IL-6 has been shown to increase migration and invasion in HTR-8/SVneo cells (Jovanovic et al., 2010; Jovanovic and Vicovac, 2009) and in JEG-3 choriocarcinoma cells (Dubinsky et al., 2010). "
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