LAUSR

Granulosa cells play a crucial role in the development of follicles, and their cell apoptosis in the porcine ovary is a major contributor to follicular atresia. Here, we provide a new mechanism for follicular atresia by describing a crucial mechanism by which peroxynitrite anion (OONO-) may cause granulosa cell death. We discovered that Nitric Oxide, oxidative stress level, and OONO- were positively correlated with porcine follicular atresia, which was accompanied by high expression of MMP2 and MMP9. We created a model of OONO--induced apoptosis in granulosa cells and discovered that OONO- could boost the expression of MMP2 and MMP9, and increase the expression of pro-apoptotic proteins and DNA damage. Furthermore, by inhibiting the activities of MMP2 and MMP9, we found SB-3CT alleviated the decrease in cell survival rates and DNA damage caused by OONO-, which may have been impacted by reducing the cleavage of PARP1 by MMP2 and MMP9. Therefore, our findings imply that OONO- can cause DNA damage to granulosa cells, participating in mediating the expression of pro-apoptotic proteins, and inhibiting DNA repair by preventing the activity of PARP1 through MMP2 and MMP9. These results help explain how OONO-/MMP2/MMP9 affects porcine follicular atresia and granulosa cell apoptosis.