Mechanisms and reversibility of nicotine-induced spermatogenesis impairment and DNA methylation changes
Abstract Smoking among men of childbearing age poses a significant threat to their reproductive health. Nicotine, the primary bioactive compound in tobacco, adversely affects sperm characteristics, but mechanisms underlying its effects and if these effects are reversible upon cessation are unclear....
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08493-y |
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| author | Jiajun Cui Chenglu Wang Yuxuan Zheng Yu Zhang Sisi Luo Zhuoran Ren Xueyun Qin Mo Zhang Fang Gao Hefeng Huang Jing Shu Guolian Ding |
| author_facet | Jiajun Cui Chenglu Wang Yuxuan Zheng Yu Zhang Sisi Luo Zhuoran Ren Xueyun Qin Mo Zhang Fang Gao Hefeng Huang Jing Shu Guolian Ding |
| author_sort | Jiajun Cui |
| collection | DOAJ |
| description | Abstract Smoking among men of childbearing age poses a significant threat to their reproductive health. Nicotine, the primary bioactive compound in tobacco, adversely affects sperm characteristics, but mechanisms underlying its effects and if these effects are reversible upon cessation are unclear. We assessed the impact of nicotine exposure and its cessation on spermatogenesis and DNA methylation. Our findings revealed that nicotine exposure reduces sperm quality and leads to testicular damage. However, these effects can be reversed to some degree following nicotine cessation. In spermatogenesis, nicotine exposure reduced the proportion of somatic cells and terminal elongating spermatids, inhibited meiosis, and impeded histone to protamine transition. Additionally, it disrupted energy metabolism by interfering with the tricarboxylic acid cycle and promoting anaerobic respiration, leading to decreased ATP levels in the testes. These metabolic changes were associated with hypoxia and oxidative stress, which can be reversed post-cessation. We further found that nicotine exposure significantly altered global sperm DNA methylation patterns, and smoking cessation effectively reversed abnormal DNA methylation. Our results from both humans and mice emphasize the potential for recovery of sperm quality and epigenetic integrity after short-term smoking cessation, which is beneficial for male reproductive function as well as potentially the health of offspring. |
| format | Article |
| id | doaj-art-c9afdd5afbdf4f82b1497eb3d5709487 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-c9afdd5afbdf4f82b1497eb3d57094872025-08-20T03:43:01ZengNature PortfolioCommunications Biology2399-36422025-07-018111410.1038/s42003-025-08493-yMechanisms and reversibility of nicotine-induced spermatogenesis impairment and DNA methylation changesJiajun Cui0Chenglu Wang1Yuxuan Zheng2Yu Zhang3Sisi Luo4Zhuoran Ren5Xueyun Qin6Mo Zhang7Fang Gao8Hefeng Huang9Jing Shu10Guolian Ding11Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan UniversityCenter for Reproductive Medicine, Department of Reproductive Endocrinology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical CollegeHuman Phenome Institute, Fudan UniversityObstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan UniversityShanghai First Maternity and Infant HospitalShanghai First Maternity and Infant HospitalObstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan UniversityObstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan UniversityCenter for Reproductive Medicine, Department of Reproductive Endocrinology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical CollegeObstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan UniversityCenter for Reproductive Medicine, Department of Reproductive Endocrinology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical CollegeObstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan UniversityAbstract Smoking among men of childbearing age poses a significant threat to their reproductive health. Nicotine, the primary bioactive compound in tobacco, adversely affects sperm characteristics, but mechanisms underlying its effects and if these effects are reversible upon cessation are unclear. We assessed the impact of nicotine exposure and its cessation on spermatogenesis and DNA methylation. Our findings revealed that nicotine exposure reduces sperm quality and leads to testicular damage. However, these effects can be reversed to some degree following nicotine cessation. In spermatogenesis, nicotine exposure reduced the proportion of somatic cells and terminal elongating spermatids, inhibited meiosis, and impeded histone to protamine transition. Additionally, it disrupted energy metabolism by interfering with the tricarboxylic acid cycle and promoting anaerobic respiration, leading to decreased ATP levels in the testes. These metabolic changes were associated with hypoxia and oxidative stress, which can be reversed post-cessation. We further found that nicotine exposure significantly altered global sperm DNA methylation patterns, and smoking cessation effectively reversed abnormal DNA methylation. Our results from both humans and mice emphasize the potential for recovery of sperm quality and epigenetic integrity after short-term smoking cessation, which is beneficial for male reproductive function as well as potentially the health of offspring.https://doi.org/10.1038/s42003-025-08493-y |
| spellingShingle | Jiajun Cui Chenglu Wang Yuxuan Zheng Yu Zhang Sisi Luo Zhuoran Ren Xueyun Qin Mo Zhang Fang Gao Hefeng Huang Jing Shu Guolian Ding Mechanisms and reversibility of nicotine-induced spermatogenesis impairment and DNA methylation changes Communications Biology |
| title | Mechanisms and reversibility of nicotine-induced spermatogenesis impairment and DNA methylation changes |
| title_full | Mechanisms and reversibility of nicotine-induced spermatogenesis impairment and DNA methylation changes |
| title_fullStr | Mechanisms and reversibility of nicotine-induced spermatogenesis impairment and DNA methylation changes |
| title_full_unstemmed | Mechanisms and reversibility of nicotine-induced spermatogenesis impairment and DNA methylation changes |
| title_short | Mechanisms and reversibility of nicotine-induced spermatogenesis impairment and DNA methylation changes |
| title_sort | mechanisms and reversibility of nicotine induced spermatogenesis impairment and dna methylation changes |
| url | https://doi.org/10.1038/s42003-025-08493-y |
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