Immunity and reproduction protective effects of Chitosan Oligosaccharides in Cyclophosphamide/Busulfan-induced premature ovarian failure model mice

Frontiers in Immunology

Immunology

Xiaoyan Li¹  Tie Su²  Haifeng Ye³  Xinxin Fu⁴  Yaoqi Huang⁵  Yuehui Zheng⁶  Xuelian Du⁶  Zhisheng Zhong⁶  Chuan Hu⁷ 

[1] Biobank center, The Second Affiliated Hospital of Nanchang University, Nanchang, China;Reproductive Health Department, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China;Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan;Department of Pathology, Yingtan People’s Hospital, Yingtan, China;Institute of Regenerative Biology and Medicine (IRBM), Helmholtz Zentrum München, Munich, Germany;National Demonstration Center for Clinical Teaching & Training, Xiang’an Hospital of Xiamen University, Xiamen, China;Reproductive Center of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang, China;Reproductive Health Department, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China;School of Basic Medicine, Nanchang University, Nanchang, China;

关键词: chitosan oligosaccharides;    premature ovarian failure;    ovarian function;    immunological function;    prophylaxis;    therapy;   

DOI  :  10.3389/fimmu.2023.1185921

 received in 2023-03-14, accepted in 2023-04-26,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionPremature ovarian failure (POF) is a major cause of infertility among women of reproductive age. Unfortunately, there is no effective treatment available currently. Researchers have shown that immune disorders play a significant role in the development of POF. Moreover, growing evidence suggest that Chitosan Oligosaccharides (COS), which act as critical immunomodulators, may have a key role in preventing and treating a range of immune related reproductive diseases.MethodsKM mice (6-8 weeks) received a single intraperitoneal injection of cyclophosphamide (CY, 120mg/kg) and busulfan (BUS, 30mg/kg) to establish POF model. After completing the COS pre-treatment or post-treatment procedures, peritoneal resident macrophages (PRMs) were collected for neutral erythrophagocytosis assay to detect phagocytic activity. The thymus, spleen and ovary tissues were collected and weighed to calculate the organ indexes. Hematoxylin-eosin (HE) staining was performed to observe the histopathologic structure of those organs. The serum levels of estrogen (E2) and progesterone (P) were measured via the enzyme-linked immunosorbent assay (ELISA). The expression levels of immune factors including interleukin 2 (IL-2), interleukin 4 (IL-4), and tumor necrosis factor α (TNF-α), as well as germ cell markers Mouse Vasa Homologue (MVH) and Fragilis in ovarian tissue, were analyzed by Western blotting and qRT-PCR. In addition, ovarian cell senescence via p53/p21/p16 signaling was also detected.ResultsThe phagocytic function of PRMs and the structural integrity of thymus and spleen were preserved by COS treatment. The levels of certain immune factors in the ovaries of CY/BUS- induced POF mice were found to be altered, manifested as IL-2 and TNF-α experiencing a significant decline, and IL-4 presenting a notable increase. Both pre-treatment and post-treatment with COS were shown to be protective effects against the damage to ovarian structure caused by CY/BUS. Senescence-associated β-galactosidase (SA-β-Gal) staining results showed that COS prevents CY/BUS-induced ovarian cell senescence. Additionally, COS regulated estrogen and progesterone levels, enhanced follicular development, and blocked ovarian cellular p53/p21/p16 signaling which participating in cell senescence.ConclusionCOS is a potent preventative and therapeutic medicine for premature ovarian failure by enhancing both the ovarian local and systemic immune response as well as inhibiting germ cell senescence.

【 授权许可】

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Copyright © 2023 Li, Ye, Su, Hu, Huang, Fu, Zhong, Du and Zheng