OONO/MMP2/MMP9 pathway-mediated apoptosis of porcine granulosa cells is associated with DNA damage

in Reproduction
Authors:
Kun LeiCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China

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Quanwei WeiCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China

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Ying ChengCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China

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Zhe WangCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China

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Haoze WuCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China

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Fang ZhaoInstitute of Animal Science, Jiangsu Academy of Agricultural Sciences, Nanjing, China

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Wei DingAnimal Husbandry and Veterinary College, Jiangsu Vocational College Agriculture and Forestry, Jurong, China

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Fangxiong ShiCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China

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https://orcid.org/0000-0001-6271-6184
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Correspondence should be addressed to F Shi; Email: fxshi@njau.edu.cn

*(K Lei and Q Wei contributed equally to this work)

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In brief

The apoptosis of granulosa cells (GCs) is the main reason for porcine follicular atresia. This study provides a novel mechanism for peroxynitrite anion-mediated GC apoptosis and follicular atresia in porcine ovary.

Abstract

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 GC 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 matrix metalloproteinase 2 (MMP2) and MMP9. We created a model of OONO-induced apoptosis in GCs 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 that SB-3CT (a specific inhibitor for MMP2 and MMP9) 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 GCs, 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 GC apoptosis.

 

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