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Pentoxifylline attenuates HPV-16 associated necrosis in placental trophoblasts

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Human papillomaviruses (HPV) have been associated with placental inflammation resulting in high-risk preterm birth. The premise for this study was that treatment with anti-inflammatory pentoxifylline would inhibit HPV-mediated placental cell death. The objectives were: (1) to study the effects of HPV-16 exposure on trophoblast cells and (2) to evaluate pentoxifylline in preventing the damaging effects of HPV-16.

Methods

Mouse embryos (1-cell) were cultured (G1plus medium, 72 h, 37 °C, 5 % CO2 in air), divided into four groups at blastocyst-stage and incubated to implantation stage. Implanted trophoblasts were exposed to either HPV-16 (group 1), concomitant HPV-16 and 3 mM pentoxifylline (group 2), 3 mM pentoxifylline only (group 3) or control medium (group 4) and further incubated for 24 h. HPV-16 were from SiHa cell lysates. Trophoblast structural integrity was assessed by morphometric analysis while apoptosis and necrosis were detected using dual-stain fluorescence assay.

Results

Trophoblast outgrowth was reduced by 90 % (P < 0.05) in HPV-16 presence (629 ± 265 µ2, mean + SEM) when compared with controls (6,456 ± 795 µ2). Pentoxifylline attenuated the effects of HPV-16 (4,308 ± 362 µ2). Nuclear size of HPV-16 infected trophoblasts was smallest among the groups (P < 0.005). HPV-16 decreased cell viability and increased necrosis but not apoptosis. Pentoxifylline prevented HPV-16 associated necrosis in trophoblasts.

Conclusions

HPV-16 decreased nuclear size and trophoblast outgrowth but these effects were attenuated by the phosphodiesterase inhibitor, pentoxifylline. The action of HPV-16 on trophoblasts was increased cell necrosis suggesting that HPV-16 pathogenesis involved either cAMP inhibition and/or activated TNF pathways.

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Acknowledgments

The SiHa cells were kindly donated by Drs. Duerksen-Hughes and her laboratory team, the Department of Basic Sciences in the Division of Biochemistry at Loma Linda University, CA, USA.

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Loma Linda University School of Medicine, 11370 Anderson St., Suite 3950, Loma Linda, CA, 92354, USA

    Sarah S. Chen, Barry S. Block & Philip J. Chan

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  1. Sarah S. Chen
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  2. Barry S. Block
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  3. Philip J. Chan
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Correspondence to Philip J. Chan.

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Chen, S.S., Block, B.S. & Chan, P.J. Pentoxifylline attenuates HPV-16 associated necrosis in placental trophoblasts. Arch Gynecol Obstet 291, 647–652 (2015). https://doi.org/10.1007/s00404-014-3471-6

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  • DOI: https://doi.org/10.1007/s00404-014-3471-6

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