Defective 3A trophoblast-endometrial cell adhesion and altered 3A growth and survival by human papillomavirus type 16 oncogenes.

Human papillomaviruses (HPVs) are found in trophoblasts of spontaneous abortions and replicate in these cells in culture. We used recombinant adeno-associated viruses (rAAV) to introduce the HPV-16 E6 and E7 oncogenes into 3A trophoblasts. AAV/E7/Neo-infected 3A trophoblasts died rapidly, but AAV/E6/Neo- and AAV/E6-E7/Neo-infected cells grew more rapidly than AAV/Neo-infected 3A cells and parental 3A. After G418 selection, the resulting E6-E7/3A and E6/3A cell lines were found to be highly defective for binding RL95 and HEC endometrial cells compared to Neo/3A and parental 3A. Serum requirements and soft agar colony formation analysis showed that E6-E7/3A had the most malignant phenotype, followed by E6/3A, with parental 3A cells having the lowest. E6/3A and E6-E7/3A were also immortal. Thus, HPV-16 oncogene expression may lead to outright trophoblast death, defective endometrial cell recognition, or a malignant phenotype. Any of these changes might lead to disruption/dysfunction of the trophoblast layer/gestational loss.