2. Academic Validation
  3. Puerarin improves busulfan-induced disruption of spermatogenesis by inhibiting MAPK pathways

Puerarin improves busulfan-induced disruption of spermatogenesis by inhibiting MAPK pathways

  • Biomed Pharmacother. 2023 Jul 27;165:115231. doi: 10.1016/j.biopha.2023.115231.
Hai-Tao Li 1,  Kun Zhong 1,  Yun-Fei Xia 2,  Jian Song 3,  Xiao-Qing Chen 4,  Wei Zhao 5,  Xu-Hui Zeng 6,  Tian-Xing Chen 7
Affiliations

Affiliations

  • 1 Medical School, Institute of Reproductive Medicine, Nantong University, Nantong 226001, Jiangsu, China.
  • 2 Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong University, Nantong 226001, China.
  • 3 Reproductive Medicine Center, Affiliated Hospital of Nantong University, Nantong University, Nantong 226001, China.
  • 4 Human Resources Division and Clinical Research Center, Affiliated Hospital of Nantong University, Nantong University, Nantong 226001, China.
  • 5 School of Laboratory Medicine, Chengdu Medical College, Chengdu, China. Electronic address: zw198626520@126.com.
  • 6 Medical School, Institute of Reproductive Medicine, Nantong University, Nantong 226001, Jiangsu, China. Electronic address: zengxuhui@ntu.edu.cn.
  • 7 Medical School, Institute of Reproductive Medicine, Nantong University, Nantong 226001, Jiangsu, China. Electronic address: chentxidea@163.com.
PMID: 37516022 DOI: 10.1016/j.biopha.2023.115231
Abstract

Male infertility is a global concern, with a noticeable increase in the decline of spermatogenesis and sperm quality. However, there are limited clinically effective treatments available. This study aimed to investigate the potential effectiveness of puerarin in treating male infertility, which leads to gonadal changes. The results obtained from various analyses such as CASA, immunofluorescence, DIFF-Quick, hematoxylin and eosin (H&E), and periodic acid-Schiff (PAS) staining demonstrated that puerarin supplementation significantly alleviated the busulfan-induced reduction in spermatogenesis and sperm quality in both young and adult mice. Furthermore, puerarin exhibited a marked improvement in the damage caused by busulfan to the architecture of seminiferous tubules, causal epididymis, blood-testicular barrier (BTB), as well as spermatogonia and Sertoli cells. Similarly, puerarin significantly reduced the levels of total antioxidant capacity (T-AOC), malondialdehyde (MDA), and Caspase-3 in the testes of busulfan-induced mice, as determined by microplate reader analysis. Additionally, RNA-seq data, RT-qPCR, and western blotting revealed that puerarin restored the abnormal gene expressions induced by busulfan to nearly healthy levels. Notably, puerarin significantly reversed the impact of busulfan on the expression of marker genes involved in spermatogenesis and oxidative stress. Moreover, puerarin suppressed the phosphorylation of p38, ERK1/2, and JNK in the testes, as observed through testicular analysis. Consequently, this study concludes that puerarin may serve as a potential alternative for treating busulfan-induced damage to male fertility by inactivating the testicular MAPK pathways. These findings may pave the way for the use of puerarin in addressing chemotherapy- or Other factors-induced male infertility in humans.

Keywords

MAPK pathways; Puerarin; Sertoli cells; Spermatogenesis; Spermatogonia.

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