2. Academic Validation
  3. Suppressed testicular macrophage M1 polarization by HDAC5 enforces insensitivity to LPS-elicited blood-testis barrier damage

Suppressed testicular macrophage M1 polarization by HDAC5 enforces insensitivity to LPS-elicited blood-testis barrier damage

  • Food Chem Toxicol. 2024 Aug 14:192:114940. doi: 10.1016/j.fct.2024.114940.
Hao Li 1,  Yi-Fan Hu 2,  Xin-Run Wang 1,  Kong-Wen Ouyang 2,  Hua Wang 3,  Kai-Wen Wang 1,  Wei Chang 1,  Jin Zhang 1,  Zhi Yuan 1,  Yong-Wei Xiong 1,  Hua-Long Zhu 1,  Lan Yang 4,  Hua Wang 5
Affiliations

Affiliations

  • 1 Department of Toxicology, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei, 230000, China; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei, 230000, China.
  • 2 Department of Toxicology, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei, 230000, China; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei, 230000, China; Wuxi Maternity and Child Health Care Hospital, Women's Hospital of Jiangnan University, Jiangnan University, Wuxi, 214000, China.
  • 3 Department of Toxicology, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei, 230000, China; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei, 230000, China; Department of Respiratory Medicine, Anhui Provincial Children's Hospital, Hefei, 230000, China.
  • 4 Wuxi Maternity and Child Health Care Hospital, Women's Hospital of Jiangnan University, Jiangnan University, Wuxi, 214000, China. Electronic address: lilylan5930@sina.com.
  • 5 Department of Toxicology, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei, 230000, China; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei, 230000, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, Hefei, 230000, China. Electronic address: wanghuadev@ahmu.edu.cn.
PMID: 39151879 DOI: 10.1016/j.fct.2024.114940
Abstract

Infertility caused by lipopolysaccharide (LPS) exposure due to Infection is endangering male fertility worldwide, but the mechanism remains unclear. The blood-testis barrier (BTB) is essential for maintaining spermatogenesis and male fertility. In the present study, we showed that LPS (5.0 mg/kg) treatment markedly down-regulated the expression of BTB-related proteins, expanded the biotin penetration distance and caused histopathological injury in seminiferous tubules in mouse testes. Notably, testicular macrophage M1 polarization induced by LPS seems to be related to BTB damage, which was well confirmed by co-culture of RAW264.7 and TM4 cells in vitro. Interestingly, a low-dose LPS (0.1 mg/kg) pretreatment attenuated down-regulation of BTB-related proteins expression and histopathological injury and shorten biotin penetration distance in seminiferous tubules caused by LPS. Correspondingly, a low-dose LPS pretreatment suppresses testicular macrophage M1 polarization induced by LPS in mouse testes. Further experiments revealed that histone deacetylase 5 (HDAC5) was markedly down-regulated at 2 h and slightly down-regulated at 8 h, but up-regulated at 24 h in mouse testes after LPS treatment. Additionally, low-dose LPS pretreatment against the down-regulation of HDAC5 protein caused by LPS treatment. Notably, the suppressed testicular macrophage M1 polarization by low-dose LPS pretreatment was broken by BRD4354, a specific inhibitor of HDAC5 in vitro. These results suggest suppressed testicular macrophage M1 polarization by HDAC5 enforces insensitivity to LPS-elicited BTB damage.

Keywords

Blood-testis barrier; HDAC; LPS tolerance; M1/M2 polarization; Macrophage; Male reproduction toxicity.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-112719
    99.66%, HDAC 抑制剂
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z