Abstract
Whether HPV is causative of pregnancy complications is uncertain. E6 and E7 affect functions underling preeclampsia (PET) in cultured trophoblasts, but whether E6 and E7 is produced in the placenta is uncertain. Here, we investigated whether E6/E7 was expressed in the placentae from pregnancies with PET, other pregnancy complications (fetal growth restriction (FGR) and diabetes mellitus), and uncomplicated pregnancies. Placental tissues collected from two geographical locations were subjected to RNAscope analyses of high- and low- risk E6/E7, and individual HPV types identified using an HPV array. High-risk E6/E7 expression was increased in both PET cohorts, (81% and 86% of patients positive for high-risk HPV DNA compared to 13% of control patients). Various HPV types were identified. Although HPV 18 was the most frequent in all cohorts, the majority of individuals had multiple HPV types (55% of the PET compared to 25% of the control cohort). Further evidence that E6 and E7 is present early when placental pathology underlying preeclampsia is established, is provided with the finding of high-risk E6/E7 in the first-trimester placenta anchoring trophoblast. In conclusion, E6/E7 expression and multiple HPV types were frequent in placentae from preeclampsia-complicated pregnancies.
Highlights
The two cohorts from Japan were included to investigate the presence of E6/E7 in placentae from a different geographical location and included a cohort of placentae complicated with hypertensive disorders in pregnancy (HDP) and a control cohort without complications
E6/E7 was frequently expressed in Human papillomavirus (HPV) DNA-positive placentae from two cohorts of PET-complicated pregnancies, but it was rare in the placentae from uncomplicated pregnancies, including those with high-risk HPV DNA
The results from the current study suggest that E6/E7 is not always expressed in HPV-positive cases and may be more likely in PET compared to other pregnancy complications with HPV-positive placentae, which adds further complexities to deciphering how placental HPV E6/E7 expression is governed
Summary
HPV infection rates are higher [1,2] and are associated with early and late-pregnancy complications, including PET, fetal growth restriction (FGR), and miscarriages [3,4,5,6,7,8,9,10,11,12,13,14,15,16]. High-risk E6 and E7 proteins have well-characterized roles in cell transformation in a cancer context, but they may affect placental function. HPV E6 and E7 proteins when introduced into trophoblasts reduced cell invasion, migration, and survival and poorly adhered to endothelial cells suggesting high-risk HPV affects functions underpinning an increased risk of PET [8,19,20]
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