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. 2024 Sep;50(9):1655-1666.
doi: 10.1111/jog.16004. Epub 2024 Jun 27.

Role of DNA damage response in cyclophosphamide-induced premature ovarian failure in mice

Yi Song  1   2   3 , Zhong Guo  2   3 , Lei Song  2 , Jian-Xiu Ma  2   3 , Yan-Qing Ma  2 , Li-Na Shang  2 , Ya-Ping Meng  2 , Zi-Qi Fan  2 , Ming-Hui Hao  2 , Jin Zhao  1   2   3
Affiliations

Role of DNA damage response in cyclophosphamide-induced premature ovarian failure in mice

Yi Song et al. J Obstet Gynaecol Res. 2024 Sep.

Abstract

Aim: To investigate the DNA damage response (DDR) in a cyclophosphamide (CTX)-induced mouse model of premature ovarian failure (POF).

Methods: The POF model was established by injecting mice with CTX. The body, ovarian weights, the estrus cycle, and pathological changes of the ovaries were recorded. The serum levels of 17 β-estradiol (E2) and follicle-stimulating hormone (FSH) were measured. The expression of Ki67, β-galactosidase (β-gal), p21, p53, γH2AX, and pATM in ovarian tissues was detected by immunohistochemistry. The expression of β-gal, γH2AX, and pATM was analyzed by immunofluorescence staining of primary cultured granulosa cells (GCs).

Results: The body and ovarian weights decreased, the estrus cycles were erratic, and the FSH level increased, whereas the E2 level decreased in POF mice compared to controls. The pathological consequences of POF revealed an increase in atretic follicles, corpus luteum, and primordial follicles and a decrease in the number of primary, secondary, and tertiary follicles. Ki67 expression was reduced, β-gal, p21, p53, γH2AX, and pATM expression were elevated in the ovaries of POF mice. The expression of β-gal, γH2AX, and pATM increased in GCs with the concentration in a time-dependent manner.

Conclusion: In total, CTX induced POF in mice, which was mediated by the DDR pathway of ATM-P53-P21.

Keywords: ATM–P53–P21 signaling pathway; DNA damage response; cyclophosphamide; premature ovarian failure; γH2AX.

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References

REFERENCES

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–249.
    1. Dommett RM, Pring H, Cargill J, Beynon P, Cameron A, Cox R, et al. Achieving a timely diagnosis for teenagers and young adults with cancer: the ACE “too young to get cancer?” study. BMC Cancer. 2019;19:616.
    1. Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70:145–164.
    1. Zheng Q, Fu XY, Jiang JZ, Zhang N, Zou LB, Wang WQ, et al. Umbilical cord mesenchymal stem cell transplantation prevents chemotherapy‐induced ovarian failure via the NGF/TrkA pathway in rats. Biomed Res Int. 2019;2019:1–9.
    1. Feng RM, Zong YN, Cao SM, Xu RH. Current cancer situation in China: good or bad news from the 2018 global cancer statistics? Cancer Commun. 2019;39:12.