Viral Infection of Cumulus Cells Impairs the Developmental Competence of Ovulated Mouse Oocytes

Viral infections in the female reproductive tract pose significant risks to fertility; however, their specific impacts on ovulated oocytes and the role of the surrounding cumulus cells remain unclear. In this study, we examined viral infection experiments and gene expression analyses to investigate the cell type-specific antiviral responses of mouse cumulus-oocyte complexes (COCs) using vesicular stomatitis virus (VSV) as a model RNA virus. Although ovulated oocytes expressed the cytosolic viral receptor retinoic acid-inducible gene-I, they lacked melanoma differentiation-associated gene 5 and laboratory of genetics and physiology 2 gene, which are present in cumulus cells. Exposure of COCs to VSV significantly impaired preimplantation development, reducing cleavage and blastocyst formation rates. Interestingly, no direct viral infection was detected in oocytes or early embryos, possibly due to the physical barrier of the zona pellucida. Direct exposure of denuded oocytes to VSV failed to induce antiviral gene expression or developmental defects. In contrast, co-culturing uninfected oocytes with VSV-infected cumulus cells resulted in developmental impairment. Infected cumulus cells exhibited robust antiviral responses and significantly upregulated retinoic acid-inducible gene-i, interferon-b, interleukin (Il)-6, and tumor necrosis factor-a levels. Correspondingly, oocytes and zygotes expressed the IL-6 receptor subunits Il6ra and Gp130. Overall, viral infection of cumulus cells impaired oocyte developmental competence via indirect paracrine signaling and identified IL-6 as a candidate mediator. These findings provide insights into the mechanisms by which the maternal inflammatory microenvironment influences early embryonic success and highlight the protective yet vulnerable nature of COCs during viral challenge.