Pyrroloquinoline quinone activates lactate production and inhibits NLRP3 to improve the apoptosis of granulosa cells in POI rats

Author:

Liu Ke1,Huo Peng2,Li BaoXiang1,Li Tianlong1,Ma Yue1,Zhong Ou1,Li Wanhan1,Zhang Shun3,Chen Xi1,Lei Xiaocan1

Affiliation:

1. University of South China and Yueyang Women & Children’s Medical Center Yueyang

2. Guilin Medical University

3. The Affiliated Hospital of Guilin Medical University

Abstract

Abstract

Chemotherapy-induced premature ovarian insufficiency (POI) is an extreme form of reproductive aging in women, while the inflammatory factors manifest a vital cause of ovarian aging and serve as a research hotspot. However, there is still no effective method to restore the ovarian reserve. In the present study, we investigated the potential association between pyrroloquinoline quinone (PQQ) and chemotherapy-induced POI. To investigate this, a POI rat model was established by cyclophosphamide (CTX) successfully, we demonstrated that PQQ intervention reduced the ovarian injury and improved ovarian function, as well as increased the lactate levels and up-regulated the expression of key rate-limiting enzymes of glycolysis, while inhibited the expression of inflammatory factors such as NLRP3 and so on in the ovarian aging rats. To further explore the mechanisms, KGN cells were treated with Lipopolysaccharide (LPS) to mimic the inflammatory environment. PQQ alleviated the inflammation level and enhanced the glycolysis rate of KGN cells treated by LPS, meanwhile an identical effect was detected by inhibiting NLRP3. Furthermore, PQQ acted as a molecule which could activated the process of glycolysis. Collectively, our findings show that PQQ as an antioxidant may effectively restore the ovarian reserve function, which suggesting that great clinical significance to apply PQQ for prevention and treatment of chemotherapy-induced premature ovarian insufficiency in the future.

Publisher

Springer Science and Business Media LLC

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