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单二乙甲酸 (MEHP) 在青春期大鼠中可逆地破坏血屏障 (BTB)

Richa Tiwary¹, John H Richburg¹

¹Center for Molecular and Cellular Toxicology, Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas.

Toxicological sciences : an official journal of the Society of Toxicology

|November 9, 2023

概括

暴露于单二甲基甲酸盐 (MEHP) 破坏了青春期前大鼠的血液-丸屏障 (BTB),但不是成年大鼠. 这种干扰是可逆的,并且与紧密结合蛋白的变化有关.

科学领域:

生殖毒理学生殖毒理学
内分泌学在内分泌学.
细胞生物学细胞生物学

背景情况:

血液丸屏障 (BTB) 对于男性生育至关重要,它保护发育中的精子细胞.
环境中有毒的物质,如二甲二乙甲酸盐 (DEHP),可能会损害BTB的完整性.
已知DEHP的活性代谢物MEHP会影响塞尔托利细胞的功能.

研究的目的:

调查MEHP对青春期前和成年大鼠BTB完整性的影响.
为了确定MEHP诱导的BTB中断中涉及的特定信号传导通路.

主要方法:

鼠 (青春期和成年) 用MEHP进行治疗.
评估了BTB完整性的功能性和通过检查紧结蛋白 (ZO-1,ocludin).
监测了MAPK通路的激活.

主要成果:

在青春期前的老鼠中,MEHP破坏了BTB的完整性,导致ZO-1和奥克卢丁错位和精子细胞脱落.
成年大鼠在暴露于MEHP后没有出现BTB干扰.
在青春期前的老鼠中,MEHP诱导了p44/42 MAPK通路的短暂激增.
在MEHP暴露后5周内恢复了BTB完整性.

结论:

急性MEHP暴露破坏了青春期前大鼠BTB的功能完整性,但不是成年大鼠.
这种干扰涉及紧结蛋白的改变,与MAPK通路激活有关.
在青春期前的老鼠中,MEHP对BTB的影响是可逆的.

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