Sperm miR‐142‐3p Reprogramming Mediates Paternal Pre‐Pregnancy Caffeine Exposure‐Induced Non‐Alcoholic Steatohepatitis in Male Offspring Rats
Abstract Numerous studies have suggested a strong association between paternal adverse environmental exposure and increased disease susceptibility in offspring. However, the impact of paternal pre‐pregnant caffeine exposure (PPCE) on offspring health remains unexplored. This study elucidates the spe...
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Wiley
2024-11-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202405592 |
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| author | Cong Zhang Yu Guo Yi Liu Kexin Liu Wen Hu Hui Wang |
| author_facet | Cong Zhang Yu Guo Yi Liu Kexin Liu Wen Hu Hui Wang |
| author_sort | Cong Zhang |
| collection | DOAJ |
| description | Abstract Numerous studies have suggested a strong association between paternal adverse environmental exposure and increased disease susceptibility in offspring. However, the impact of paternal pre‐pregnant caffeine exposure (PPCE) on offspring health remains unexplored. This study elucidates the sperm reprogramming mechanism and potential intervention targets for PPCE‐induced non‐alcoholic steatohepatitis (NASH) in offspring. Here, male rats are administrated caffeine (15–60 mg kg−1/d) by gavage for 8 weeks and then mated with females to produce offspring. This study finds that NASH with transgenerational inheritance occurred in PPCE adult offspring. Mechanistically, a reduction of miR‐142‐3p is implicated in the occurrence of NASH, characterized by hepatic lipid metabolism dysfunction and chronic inflammation through an increase in ACSL4. Conversely, overexpression of miR‐142‐3p mitigated these manifestations. The origin of reduced miR‐142‐3p levels is traced to hypermethylation in the miR‐142‐3p promoter region of parental sperm, induced by elevated corticosterone levels rather than by caffeine per se. Similar outcomes are confirmed in offspring conceived via in vitro fertilization using miR‐142‐3pKO sperm. Overall, this study provides the first evidence of transgenerational inheritance of NASH in PPCE offspring and identifies miR‐142‐3p as a potential therapeutic target for NASH induced by paternal environmental adversities. |
| format | Article |
| id | doaj-art-9625d40e82a846f3b51f18e10b7d3fb7 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-9625d40e82a846f3b51f18e10b7d3fb72025-08-20T03:52:43ZengWileyAdvanced Science2198-38442024-11-011142n/an/a10.1002/advs.202405592Sperm miR‐142‐3p Reprogramming Mediates Paternal Pre‐Pregnancy Caffeine Exposure‐Induced Non‐Alcoholic Steatohepatitis in Male Offspring RatsCong Zhang0Yu Guo1Yi Liu2Kexin Liu3Wen Hu4Hui Wang5Department of Pharmacology School of Basic Medical Sciences Wuhan University Wuhan 430071 ChinaDepartment of Pharmacology School of Basic Medical Sciences Wuhan University Wuhan 430071 ChinaDepartment of Pharmacology School of Basic Medical Sciences Wuhan University Wuhan 430071 ChinaDepartment of Pharmacology School of Basic Medical Sciences Wuhan University Wuhan 430071 ChinaHubei Provincial Key Laboratory of Developmentally Originated Disease Wuhan 430071 ChinaDepartment of Pharmacology School of Basic Medical Sciences Wuhan University Wuhan 430071 ChinaAbstract Numerous studies have suggested a strong association between paternal adverse environmental exposure and increased disease susceptibility in offspring. However, the impact of paternal pre‐pregnant caffeine exposure (PPCE) on offspring health remains unexplored. This study elucidates the sperm reprogramming mechanism and potential intervention targets for PPCE‐induced non‐alcoholic steatohepatitis (NASH) in offspring. Here, male rats are administrated caffeine (15–60 mg kg−1/d) by gavage for 8 weeks and then mated with females to produce offspring. This study finds that NASH with transgenerational inheritance occurred in PPCE adult offspring. Mechanistically, a reduction of miR‐142‐3p is implicated in the occurrence of NASH, characterized by hepatic lipid metabolism dysfunction and chronic inflammation through an increase in ACSL4. Conversely, overexpression of miR‐142‐3p mitigated these manifestations. The origin of reduced miR‐142‐3p levels is traced to hypermethylation in the miR‐142‐3p promoter region of parental sperm, induced by elevated corticosterone levels rather than by caffeine per se. Similar outcomes are confirmed in offspring conceived via in vitro fertilization using miR‐142‐3pKO sperm. Overall, this study provides the first evidence of transgenerational inheritance of NASH in PPCE offspring and identifies miR‐142‐3p as a potential therapeutic target for NASH induced by paternal environmental adversities.https://doi.org/10.1002/advs.202405592ACSL4miR‐142‐3pnon‐alcoholic steatohepatitispaternal pre‐pregnant caffeine exposuresperm reprogramming |
| spellingShingle | Cong Zhang Yu Guo Yi Liu Kexin Liu Wen Hu Hui Wang Sperm miR‐142‐3p Reprogramming Mediates Paternal Pre‐Pregnancy Caffeine Exposure‐Induced Non‐Alcoholic Steatohepatitis in Male Offspring Rats Advanced Science ACSL4 miR‐142‐3p non‐alcoholic steatohepatitis paternal pre‐pregnant caffeine exposure sperm reprogramming |
| title | Sperm miR‐142‐3p Reprogramming Mediates Paternal Pre‐Pregnancy Caffeine Exposure‐Induced Non‐Alcoholic Steatohepatitis in Male Offspring Rats |
| title_full | Sperm miR‐142‐3p Reprogramming Mediates Paternal Pre‐Pregnancy Caffeine Exposure‐Induced Non‐Alcoholic Steatohepatitis in Male Offspring Rats |
| title_fullStr | Sperm miR‐142‐3p Reprogramming Mediates Paternal Pre‐Pregnancy Caffeine Exposure‐Induced Non‐Alcoholic Steatohepatitis in Male Offspring Rats |
| title_full_unstemmed | Sperm miR‐142‐3p Reprogramming Mediates Paternal Pre‐Pregnancy Caffeine Exposure‐Induced Non‐Alcoholic Steatohepatitis in Male Offspring Rats |
| title_short | Sperm miR‐142‐3p Reprogramming Mediates Paternal Pre‐Pregnancy Caffeine Exposure‐Induced Non‐Alcoholic Steatohepatitis in Male Offspring Rats |
| title_sort | sperm mir 142 3p reprogramming mediates paternal pre pregnancy caffeine exposure induced non alcoholic steatohepatitis in male offspring rats |
| topic | ACSL4 miR‐142‐3p non‐alcoholic steatohepatitis paternal pre‐pregnant caffeine exposure sperm reprogramming |
| url | https://doi.org/10.1002/advs.202405592 |
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