Skip to main content

Advertisement

SpringerLink
Log in

HPV-16 exposed mouse embryos: a potential model for pregnancy wastage

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Placentas from spontaneous abortions and preterm deliveries have a higher prevalence of Human papillomavirus (HPV) compared to placentas from elective abortions and term births. The objective was to determine the effects of HPV-16 on the adhesion and implantation properties of early embryo trophoblasts.

Methods

Two-cell mouse embryos were cultured (medium G2, 5 % CO2, 37 °C) for 72–96 h and exposed to either HPV-16 rich SiHa cell lysates which were refrigerated after mechanical lysis, thawed lysates which had been frozen for freeze/thaw lysis method, or control medium, incubated (4–5 days) and evaluated by microscopy (N = 96 embryos, 3 repeated experiments). Trophoblasts were stained and images were digitized. Adhesion and dimension data were analyzed by Chi-square and t test, respectively.

Results

HPV-16 exposed embryos exhibited less adhesion through reduced implantation compared with the control (combined lysates 53.8 vs. 85.7 %, P < 0.05). Refrigerated and thawed lysate groups had similar reduced implantations (58.3 vs. 50.0 %). Of the embryos with implantation, 100 % in the refrigerated lysates were noted to have loose or abnormal adhesion. This was measured when embryos were noted to be lost after washes with HTF. There was no difference in trophoblast viability among the groups. Total trophoblast area was greater in the HPV-16 exposed frozen lysate group (1,881.8 ± 605.3 vs. control 848.8 ± 298.0 square units, mean ± SEM).

Conclusions

HPV-16 inhibited trophoblasts adhesion needed for normal implantation, but not embryo development. Total trophoblast spread was increased after HPV-16 exposure suggesting that HPV-16 altered trophoblast migration. These results suggest that HPV-16 may induce abnormal placental growth resulting in pregnancy wastage.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Munoz N, Castellsagué X, de Gonzalez AB, Gissmann L (2006) HPV in the etiology of human cancer. Vaccine 24:1–10

    Article  Google Scholar 

  2. Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Altekruse SF, Kosary CL, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds) SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations), National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2009_pops09/, based on November 2011 SEER data submission, posted to the SEER web site, 2012

  3. Boulenouar S, Weyn C, Van Noppen M, Moussa Ali M, Favre M, Delvenne PO, Bex F, Noël A, Englert Y, Fontaine V (2010) Effects of HPV-16 E5, E6 and E7 proteins on survival, adhesion, migration and invasion of trophoblastic cells. Carcinogenesis 31(3):473–480 [Epub 2009 Nov 16]

    Article  PubMed  CAS  Google Scholar 

  4. Gomez LM, Ma Y, Ho C, McGrath CM, Nelson DB, Parry S (2008) Placental infection with human papillomavirus is associated with spontaneous preterm delivery. Hum Reprod 23:709–715

    Article  PubMed  CAS  Google Scholar 

  5. Sarkola ME, Grénman SE, Rintala MA, Syrjnen KJ, Syrjnen SM (2008) Human papillomavirus in the placenta and umbilical cord blood. Acta Obstet Gynecol Scand 87:1181–1188

    Article  PubMed  Google Scholar 

  6. You H, Liu Y, Agrawal N, Prasad CK, Edwards JL, Osborne AF, Korourian S, Lowery CL, Hermonat PL (2008) Multiple human papillomavirus types replicate in 3A trophoblasts. Placenta 29:30–38

    Article  PubMed  CAS  Google Scholar 

  7. Weyn C, Thomas D, Jani J, Guizani M, Donner C, Van Rysselberge M, Hans C, Bossens M, Englert Y, Fontaine V (2011) Evidence of human papillomavirus in the placenta. J Infect Dis 203(3):341–343

    Article  PubMed  Google Scholar 

  8. Manavi M, Czerwenka KF, Schurz B, Knogler W, Kubista E, Reinold E (1992) Latent cervical virus infection as a possible cause of early abortion. Gynakol Geburtshilfliche Rundsch 32:84–87

    Article  PubMed  CAS  Google Scholar 

  9. Hermonat PL, Han L, Wendel PJ, Quirk JG, Stern S, Lowery CL, Rechtin TM (1997) Human papillomavirus is more prevalent in first trimester spontaneously aborted products of conception compared to elective specimens. Virus Genes 14:13–17

    Article  PubMed  CAS  Google Scholar 

  10. Uribarren-Berrueta O, Sánchez-Corona J, Montoya-Fuentes H, Trujillo-Hernández B, Vásquez C (2012) Presence of HPV DNA in placenta and cervix of pregnant Mexican women. Arch Gynecol Obstet 285(1):55–60

    Article  PubMed  CAS  Google Scholar 

  11. Brackmann KH, Green M, Wold WS, Rankin A, Loewenstein PM, Cartas MA, Sanders PR, Olson K, Orth G, Jablonska S, Kremsdorf D, Favre M (1983) Introduction of cloned human papillomavirus genomes into mouse cells and expression at the RNA level. Virology 129:12–24

    Article  PubMed  CAS  Google Scholar 

  12. Ferretti C, Bruni L, Dangles-Marie V, Pecking AP, Bellet D (2007) Molecular circuits shared by placental and cancer cells, and their implications in the proliferative, invasive and migratory capacities of trophoblasts. Hum Reprod Update 13:121–141

    Article  PubMed  CAS  Google Scholar 

  13. Hirano T, Higuchi T, Katsuragawa H, Inoue T, Kataoka N, Park KR, Ueda M, Maeda M, Fujiwara H, Fujii S (1999) CD9 is involved in invasion of human trophoblast-like choriocarcinoma cell line, BeWo cells. Mol Hum Reprod 5(2):168–174

    Article  PubMed  CAS  Google Scholar 

  14. Meissner JD (1999) Nucleotide sequences and further characterization of human papillomavirus DNA present in the CaSki, SiHa and HeLa cervical carcinoma cell lines. J Gen Virol 80:1725–1733

    PubMed  CAS  Google Scholar 

  15. Tungteakkhun SS, Filippova M, Neidigh JW, Fodor N, Duerksen-Hughes PJ (2008) The interaction between human papillomavirus type 16 and FADD is mediated by a novel E6 binding domain. J Virol 82:9600–9614

    Article  PubMed  CAS  Google Scholar 

  16. Rowland SC, Jacobson JD, Patton WC, King A, Chan PJ (2003) Dual fluorescence analysis of DNA apoptosis in sperm. Am J Obstet Gynecol 188:1156–1157

    Article  PubMed  CAS  Google Scholar 

  17. Liu Y, You H, Chiriva-Internati M, Korourian S, Lowery CL, Carey MJ, Smith CV, Hermonat PL (2001) Display of complete life cycle of human papillomavirus type 16 in cultured placental trophoblasts. Virology 290:99–105

    Article  PubMed  CAS  Google Scholar 

  18. Wang J, Mayernik L, Armant DR (2007) Trophoblast adhesion of the peri-implantation mouse blastocyst is regulated by integrin signaling that targets phospholipase C. Dev Biol 302:143–153

    Article  PubMed  CAS  Google Scholar 

  19. You H, Liu Y, Carey MJ, Lowery CL, Hermonat PL (2002) Defective 3A trophoblast–endometrial cell adhesion and altered 3A growth and survival by human papillomavirus type 16 oncogenes. Mol Cancer Res 1:25–31

    PubMed  CAS  Google Scholar 

  20. You H, Liu Y, Agrawal N, Prasad CK, Chiriva-Internati M, Lowery CL, Kay HH, Hermonat PL (2003) Infection, replication, and cytopathology of human papillomavirus type 31 in trophoblasts. Virology 316:281–289

    Article  PubMed  CAS  Google Scholar 

  21. Whiteside MA, Siegel EM, Unger ER (2008) Human papillomavirus and molecular considerations for cancer risk. Cancer 113:2981–2994

    Article  PubMed  CAS  Google Scholar 

  22. Chakraborty C, Gleeson LM, McKinnon T, Lala PK (2002) Regulation of human trophoblast migration and invasiveness. Can J Physiol Pharmacol 80(2):116–124

    Article  PubMed  CAS  Google Scholar 

  23. Rock JA, Zacur HA (1983) The clinical management of repeated early pregnancy wastage. Fertil Steril 39(2):123–140

    PubMed  CAS  Google Scholar 

  24. Terra AP, Murta EF, Maluf PJ, Caballero OL, Brait M, Adad SJ (2007) Aberrant promoter methylation can be useful as a marker of recurrent disease in patients with cervical intraepithelial neoplasia grade III. Tumori 93:572–579

    PubMed  CAS  Google Scholar 

  25. Long BR, Erickson AE, Chapman JM, Barbour JD, Vu BA, Ho EL, Lanier LL, Sauer MM, Carvalho KI, Nixon DF, Kallas EG (2010) Increased number and function of natural killer cells in human immunodeficiency virus 1-positive subjects co-infected with herpes simplex virus 2. Immunology 129:186–196

    Article  PubMed  CAS  Google Scholar 

  26. Li AS, Siu MK, Zhang H, Wong ES, Chan KY, Ngan HY, Cheung A (2008) Hypermethylation of SOX2 gene in hydatidiform mole and choriocarcinoma. Reprod Sci 15:735–744

    Article  PubMed  CAS  Google Scholar 

  27. Caberg JH, Hubert PM, Begon DY, Herfs MF, Roncarati PJ, Boniver JJ, Delvenne PO (2008) Silencing of E7 oncogene restores functional E-cadherin expression in human papillomavirus 16-transformed keratinocytes. Carcinogenesis 29:1441–1447

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The SiHa cells were kindly offered by Dr. Duerksen-Hughes and her lab, the Department of Basic Sciences in the Division of Biochemistry at Loma Linda University, CA, USA [15].

Conflict of interest

None.

Author information

Authors and Affiliations

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

    Linda J. Hong, Bryan T. Oshiro & Philip J. Chan

Authors
  1. Linda J. Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bryan T. Oshiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Philip J. Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Linda J. Hong.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hong, L.J., Oshiro, B.T. & Chan, P.J. HPV-16 exposed mouse embryos: a potential model for pregnancy wastage. Arch Gynecol Obstet 287, 1093–1097 (2013). https://doi.org/10.1007/s00404-013-2711-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-013-2711-5

Keywords

Search

Navigation