Porcine reproductive and respiratory syndrome virus (PRRSV) infection in pig herds is the primary cause of reproductive disorders in sows, posing a significant threat to the global swine industry. The infection directly impairs reproductive efficiency in sows. However, the effects of PRRSV on the reproductive system of female piglets have not been thoroughly investigated. In this study, female piglets were infected with PRRSV, and the extent of damage to the reproductive system was systematically evaluated. Following PRRSV infection, damage was observed in oocytes, luminal epithelium (LE), glandular epithelium (GE), and stromal (S) cells of the uterus, accompanied by arrested development of glands and vasculature in the uterine horns. Immunohistochemical analysis (IHC) demonstrated the localization of viral antigens within the endometrial epithelial cells of the uterine horns. PRRSV infection suppressed the expression of estrogen receptor α (ESR-α) in the uterine horns. Interestingly, the proliferation capacity of endometrial cells in the uterine horns was simultaneously reduced, and multiple genes and pathways regulating cell proliferation were also downregulated. Disruption of tight junctions (TJ) at the uterine horns further indicated compromised epithelial barrier integrity. This barrier disruption was accompanied by the initiation of a cytokine storm and enrichment of inflammation-related pathways (NF-κB, chemokine, Toll-like receptor, TNF, and JAK-STAT signaling), indicating substantial inflammatory injury consistent with viral pathology. These results demonstrate that PRRSV inflicts severe damage on the ovaries and uterus of female piglets, thereby threatening the healthy development of the sow reproductive system.
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