Dibutyl phthalate disrupts[Ca^(2+)]_(i),reactive oxygen species,[pH]_(i),protein kinases and mitochondrial activity,impairing sperm function  

作　　者：Seung Hyun Park Myung Chan Gye 

机构地区：[1]Department of Life Science and Institute for Natural Sciences,Hanyang University,Seoul 04763,Republic of Korea

出　　处：《Journal of Environmental Sciences》2025年第5期68-78,共11页环境科学学报(英文版)

基　　金：supported by the National Research Foundation of Republic of Korea(NRF)grant funded by the Republic of Korea government(MSIT)(No.2022R1A2C1007831).

摘　　要：To explore the mechanism of sperm dysfunction caused by dibutyl phthalate(DBP),the effects of DBP on intracellular[Ca^(2+)]and[pH],reactive oxygen species(ROS),lipid peroxidation(LPO),mitochondrial permeability transition pore(mPTP)opening,mitochondrial membrane potential(MMP),adenosine triphosphate(ATP)levels,phosphorylation of protein kinase A(PKA)substrate proteins and phosphotyrosine(p-Tyr)proteins,sperm motility,spontaneous acrosome reaction,and tail bending were examined in mouse spermatozoa.At 100μg/mL,DBP significantly increased tail bending and[Ca^(2+)]i.Interestingly,DBP showed biphasic effects on[pH]i.DBP at 10–100μg/mL significantly decreased sperm motility.Similarly,Ca^(2+)ionophore A23187 decreased[pH]_(i)sperm motility,suggesting that DBP-induced excessive[Ca^(2+)]_(i)decreased sperm motility.DBP significantly increased ROS and LPO.DBP at 100μg/mL significantly decreased mPTP closing,MMP,and ATP levels in spermatozoa,as did H2O2,indicative of ROS-mediatedmitochondrial dysfunction caused by DBP.DBP as well as H2O2 increased p-Tyr sperm proteins and phosphorylated PKA substrate sperm proteins.DBP at 1–10μg/mL significantly increased the spontaneous acrosome reaction,suggesting that DBP can activate sperm capacitation.Altogether,DBP showed a biphasic effect on intracellular signaling in spermatozoa.At concentrations relevant to seminal ortho-phthalate levels,DBP activates[pH]i,protein tyrosine kinases and PKA via physiological levels of ROS generation,potentiating sperm capacitation.DBP at high doses excessively raises[Ca^(2+)]_(i)and ROS and disrupts[pH]i,impairing the mitochondrial function,tail structural integrity,and sperm motility.

关 键 词：Dibutyl phthalate Reactive oxygen species(ROS) [Ca^(2+)]_(i) [pH]_(i) MITOCHONDRIA Protein kinases SPERM 

分 类 号：R69[医药卫生—泌尿科学]