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胎盘依赖RTN3L的内质网自噬在环境应激时导致胎儿睾丸发育异常。

Placental RTN3L-dependent ER-Phagy Contributes to Fetal Testicular Dysplasia Upon Environmental Stress.

作者信息

Luo Ye-Xin, Zhu Hua-Long, Huang Bin-Bin, Sun Cheng-Fang, Zhang Xin-Xin, Wang Xin-Run, Hu Yi-Fan, Zhang Xu-Dong, Xu Shen-Dong, Zhou Huan, Pan Rui, Chang Wei, Yuan Zhi, Xiong Yong-Wei, Xu Xiao-Feng, Zhao Ling-Li, Xu De-Xiang, Wang Hua

机构信息

Department of Toxicology, Center for Big Data and Population Health of IHM, School of Public, Health, Anhui Medical University, Hefei, 230022, China.

Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei, 230022, China.

出版信息

Adv Sci (Weinh). 2025 Jul;12(25):e2500924. doi: 10.1002/advs.202500924. Epub 2025 Apr 26.

DOI:10.1002/advs.202500924
PMID:40285582
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12224940/
Abstract

Prenatal environmental stress damages fetal testicular development, leading to male infertility. However, the precise mechanisms underlying the impact of gestational environmental stress on fetal testicular development require further investigation. This study demonstrates that gestational environmental stressor cadmium exposure caused placental estradiol synthesis inhibition and fetal testicular dysplasia. Gestational estradiol supplementation restores fetal testicular dysplasia caused by environmental stress-induced placental estradiol synthesis inhibition. Analysis of human placentae and cadmium-stimulated human primary placental trophoblasts confirmed that ER-phagy is associated with the inhibition of estradiol synthesis in placentae. Subsequently, the data reveals that environmental stress significantly activates RTN3L-mediated ER-phagy. RTN3L-deficient cells and placental Rtn3l-specific knockout mice confirm that environmental stress-activated RTN3L-mediated ER-phagy inhibited placental estradiol synthesis. Total N6-methyladenosine level increasing in gestational environmental stress-exposed placentae. METTL3-mediated N6-methyladenosine modification suppression obviously restrains environmental stress-activated RTN3L-dependent ER-phagy. In conclusion, gestational environmental stress activates ER-phagy by increasing placental Rtn3l mRNA N6-methyladenosine modification, inhibiting placental estradiol synthesis, and contributing to fetal testicular dysplasia. The study demonstrates the early prevention and treatment of adult male infertility from the perspective of fetal-derived diseases.

摘要

产前环境应激会损害胎儿睾丸发育，导致男性不育。然而，妊娠期环境应激对胎儿睾丸发育影响的具体机制仍需进一步研究。本研究表明，妊娠期环境应激源镉暴露会导致胎盘雌二醇合成受到抑制以及胎儿睾丸发育异常。妊娠期补充雌二醇可恢复因环境应激诱导的胎盘雌二醇合成抑制所导致的胎儿睾丸发育异常。对人胎盘和镉刺激的人原代胎盘滋养层细胞的分析证实，内质网自噬与胎盘雌二醇合成的抑制有关。随后，数据显示环境应激会显著激活RTN3L介导的内质网自噬。RTN3L缺陷细胞和胎盘Rtn3l特异性敲除小鼠证实，环境应激激活的RTN3L介导的内质网自噬抑制了胎盘雌二醇合成。妊娠期暴露于环境应激的胎盘组织中，总N6-甲基腺苷水平升高。METTL3介导的N6-甲基腺苷修饰抑制明显抑制了环境应激激活的RTN3L依赖性内质网自噬。总之，妊娠期环境应激通过增加胎盘Rtn3l mRNA的N6-甲基腺苷修饰来激活内质网自噬，抑制胎盘雌二醇合成，并导致胎儿睾丸发育异常。该研究从胎儿源性疾病的角度为成年男性不育症的早期防治提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/12224940/978f80c3084c/ADVS-12-2500924-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/12224940/fa0c9e3c9626/ADVS-12-2500924-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/12224940/978f80c3084c/ADVS-12-2500924-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/12224940/fa0c9e3c9626/ADVS-12-2500924-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/12224940/c423d3e66e65/ADVS-12-2500924-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/12224940/994f3119f25e/ADVS-12-2500924-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/12224940/37480b12b0b6/ADVS-12-2500924-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/12224940/b42deb202a64/ADVS-12-2500924-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/12224940/82c68ce361da/ADVS-12-2500924-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/12224940/f4c9548322eb/ADVS-12-2500924-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/12224940/978f80c3084c/ADVS-12-2500924-g001.jpg

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本文引用的文献

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Theranostics. 2024 Aug 6;14(12):4683-4700. doi: 10.7150/thno.99019. eCollection 2024.
2
DDRGK1-mediated ER-phagy attenuates acute kidney injury through ER-stress and apoptosis.DDRGK1 介导线粒体自噬通过内质网应激和细胞凋亡减轻急性肾损伤。
Cell Death Dis. 2024 Jan 17;15(1):63. doi: 10.1038/s41419-024-06449-4.
3
Steroidogenesis and androgen/estrogen signaling pathways are altered in in vitro matured testicular tissues of prepubertal mice.
类固醇生成和雄激素/雌激素信号通路在未成年小鼠体外成熟睾丸组织中发生改变。
Elife. 2023 Dec 14;12:RP85562. doi: 10.7554/eLife.85562.
4
Male infertility.男性不育症。
Nat Rev Dis Primers. 2023 Sep 14;9(1):49. doi: 10.1038/s41572-023-00459-w.
5
Effects of Gestational Arsenic Exposures on Placental and Fetal Development in Mice: The Role of .妊娠期砷暴露对小鼠胎盘和胎儿发育的影响： 的作用。
Environ Health Perspect. 2023 Sep;131(9):97004. doi: 10.1289/EHP12207. Epub 2023 Sep 8.
6
RNA methylation reading protein YTHDF2 relieves myocardial ischemia-reperfusion injury by downregulating BNIP3 via mA modification.RNA甲基化阅读蛋白YTHDF2通过mA修饰下调BNIP3减轻心肌缺血再灌注损伤。
Hum Cell. 2023 Nov;36(6):1948-1964. doi: 10.1007/s13577-023-00956-w. Epub 2023 Jul 28.
7
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