Male infertility is a complex reproductive disorder that impedes a huge number of couples from having children naturally in the world(Agarwal et al.,2021).As an important pathogenic factor of male infertility,spermato...Male infertility is a complex reproductive disorder that impedes a huge number of couples from having children naturally in the world(Agarwal et al.,2021).As an important pathogenic factor of male infertility,spermatogenic impairments are mainly characterized by impaired male gamete production,reduced sperm quality,or function(Tournaye et al.,2017).Spermatogenesis is a delicate and complex biological process that requires the collaboration of a large number of proteins performing different biological functions(Liu et al.,2021).展开更多
Lambda-cyhalothrin(LCT),one of the type II pyrethroids,has been widely used throughout the world.The estrogenic effect of LCT to increase cell proliferation has been well established.However,whether the estrogenic eff...Lambda-cyhalothrin(LCT),one of the type II pyrethroids,has been widely used throughout the world.The estrogenic effect of LCT to increase cell proliferation has been well established.However,whether the estrogenic effect of LCT will influence neurodevelopment has not been investigated.In addition,17β-Estradiol(E2)plays a crucial role in neurodevelopment and induces an increase in synaptic proteins.The post-synaptic density 95(PSD95)protein,which is involved in the development of the structure and function of new spines and localized with estrogen receptor α(ERα)at the post-synaptic density(PSD),was detected in our study by using hippocampal neuron cell line HT22.We found that LCT up-regulated PSD95 and ERα expression,estrogen receptor(ER)antagonist ICI182,780 and phosphatidylinositol-4;5-bisphosphate 3-kinase(PI3K)inhibitor LY294,002 blocked this effect.In addition,LCT disrupted the promotion effect of E2 on PSD95.To investigate whether the observed changes are caused by ERα-dependent signaling activation,we next detected the effects of LCT on the ERα-mediated PI3K-Protein kinase B(PKB/Akt)-eukaryotic initiation factor(e IF)4E-binding protein 1(4E-BP1)pathway.There existed an activation of Akt and the downstream factor 4E-BP1 after LCT treatment.In addition,LCT could disrupt the activation effect of E2 on the Akt pathway.However,no changes in c AMP response element-binding protein(CREB)activation and PSD95 messenger ribonucleic acid(m RNA)were observed.Our findings demonstrated that LCT could increase the PSD95 protein level via the ERα-dependent Akt pathway,and LCT might disrupt the up-regulation effect of E2 on PSD95 protein expression via this signaling pathway.展开更多
基金supported by the National Key Research and Development Program of China(2021YFC2701400 and 2021YFC2700901)the National Natural Science Foundation of China(32100480,82171607,and 81971441)+4 种基金the Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)the Scientific Research(TP202002)from Anhui Medical Universitythe China Postdoctoral Science Foundation(2020TQ0072)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019PT310002)supported by Shanghai Municipal Commission for Science and Technology Grants(19411951800)。
文摘Male infertility is a complex reproductive disorder that impedes a huge number of couples from having children naturally in the world(Agarwal et al.,2021).As an important pathogenic factor of male infertility,spermatogenic impairments are mainly characterized by impaired male gamete production,reduced sperm quality,or function(Tournaye et al.,2017).Spermatogenesis is a delicate and complex biological process that requires the collaboration of a large number of proteins performing different biological functions(Liu et al.,2021).
基金supported by the National Natural Science Foundation of China(No.H2607-30571585)
文摘Lambda-cyhalothrin(LCT),one of the type II pyrethroids,has been widely used throughout the world.The estrogenic effect of LCT to increase cell proliferation has been well established.However,whether the estrogenic effect of LCT will influence neurodevelopment has not been investigated.In addition,17β-Estradiol(E2)plays a crucial role in neurodevelopment and induces an increase in synaptic proteins.The post-synaptic density 95(PSD95)protein,which is involved in the development of the structure and function of new spines and localized with estrogen receptor α(ERα)at the post-synaptic density(PSD),was detected in our study by using hippocampal neuron cell line HT22.We found that LCT up-regulated PSD95 and ERα expression,estrogen receptor(ER)antagonist ICI182,780 and phosphatidylinositol-4;5-bisphosphate 3-kinase(PI3K)inhibitor LY294,002 blocked this effect.In addition,LCT disrupted the promotion effect of E2 on PSD95.To investigate whether the observed changes are caused by ERα-dependent signaling activation,we next detected the effects of LCT on the ERα-mediated PI3K-Protein kinase B(PKB/Akt)-eukaryotic initiation factor(e IF)4E-binding protein 1(4E-BP1)pathway.There existed an activation of Akt and the downstream factor 4E-BP1 after LCT treatment.In addition,LCT could disrupt the activation effect of E2 on the Akt pathway.However,no changes in c AMP response element-binding protein(CREB)activation and PSD95 messenger ribonucleic acid(m RNA)were observed.Our findings demonstrated that LCT could increase the PSD95 protein level via the ERα-dependent Akt pathway,and LCT might disrupt the up-regulation effect of E2 on PSD95 protein expression via this signaling pathway.
