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Effects of nicotine on porcine pre-pupertal sertoli cells: An in vitro study.
Toxicology in Vitro ( IF 3.2 ) Pub Date : 2020-05-11 , DOI: 10.1016/j.tiv.2020.104882
Lorella Marinucci 1 , Stefania Balloni 1 , Catia Bellucci 1 , Cinzia Lilli 1 , Anna Maria Stabile 2 , Mario Calvitti 1 , Maria Chiara Aglietti 3 , Angela Gambelunghe 4 , Giacomo Muzi 4 , Mario Rende 2 , Giovanni Luca 5 , Francesca Mancuso 1 , Iva Arato 1
Affiliation  

Smoke components, such as nicotine and its major metabolites, cross the blood-testis barrier and are detectable in the seminal plasma of both active smokers and individuals exposed to cigarette smoke. In vivo studies in a rat model have further demonstrated that nicotine exposure reduces the weight of the testis, as well as the number of spermatocytes and spermatids, and affects the ultrastructure of Sertoli cells (SC) - which serve as sentinels of spermatogenesis - causing intense germ cell sloughing in the tubular lumen that compromises offspring fertility. This study sought to determine the effects of nicotine on the viability and function of purified pig pre-pubertal SC. Nicotine exposure reduced the mRNA expression and protein levels of anti-Mullerian hormone (AMH) and inhibin B and impaired FSH-r sensitivity via the downregulation of FSH-r and aromatase gene expression compared to untreated SC. Overall, our study suggests that nicotine can significantly alter extracellular matrix and tight junction protein gene expression (e.g., laminin, integrin, and occludin), thus compromising cross-talk between the interstitial and tubular compartments and enhancing blood-testis barrier (BTB) permeability via downregulation of the mitogen-activated protein kinase (MAPK) pathway. These findings further elucidate a potential mechanism of action underlying nicotine exposure's detrimental effects on SC function in vivo.

中文翻译:

尼古丁对猪产前睾丸支持细胞的体外研究。

诸如尼古丁及其主要代谢产物之类的烟雾成分穿过血液-睾丸屏障,并且在活跃吸烟者和接触香烟烟雾的人的精浆中都可以检测到。在大鼠模型中进行的体内研究进一步表明,尼古丁暴露会减少睾丸的重量以及精细胞和精子细胞的数量,并影响作为精子发生前哨的Sertoli细胞(SC)的超微结构,引起强烈的管状内腔中的生殖细胞脱落会损害子代的生育能力。这项研究试图确定尼古丁对纯化的猪青春期前SC的生存力和功能的影响。与未处理的SC相比,尼古丁暴露通过下调FSH-r和芳香酶基因的表达而降低了抗穆勒激素(AMH)和抑制素B的mRNA表达和蛋白水平,并削弱了FSH-r的敏感性。总体而言,我们的研究表明,尼古丁可以显着改变细胞外基质和紧密连接蛋白基因的表达(例如层粘连蛋白,整联蛋白和闭合蛋白),从而损害间质和肾小管区室之间的串扰并增强血液-睾丸屏障(BTB)的通透性通过下调有丝分裂原激活的蛋白激酶(MAPK)途径。这些发现进一步阐明了烟碱暴露对体内SC功能的有害作用的潜在作用机理。我们的研究表明,尼古丁可以显着改变细胞外基质和紧密连接蛋白基因的表达(例如层粘连蛋白,整联蛋白和闭合蛋白),从而损害间质和肾小管区室之间的串扰并通过下调增强血液-睾丸屏障(BTB)的通透性丝裂原激活的蛋白激酶(MAPK)途径 这些发现进一步阐明了烟碱暴露对体内SC功能的有害作用的潜在作用机理。我们的研究表明,尼古丁可以显着改变细胞外基质和紧密连接蛋白基因的表达(例如层粘连蛋白,整联蛋白和闭合蛋白),从而损害间质和肾小管区室之间的串扰并通过下调增强血液-睾丸屏障(BTB)的通透性丝裂原活化蛋白激酶(MAPK)途径的研究。这些发现进一步阐明了烟碱暴露对体内SC功能的有害作用的潜在作用机理。
更新日期:2020-05-11
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