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Cigarette Smoke Exposure in Mice using a Whole-Body Inhalation System
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Trichostatin A inhibits uterine histomorphology alterations induced by cigarette smoke exposure in mice

Jingjing Ding1, Bo Liu1, Peihui Han2

  • 1Medical Research Center of Shengjing Hospital, China Medical University, Shenyang 110004, China; Key Laboratory of Research and Application of Animal Model for Environmental and Metabolic Diseases, Liaoning Province, China.

Life Sciences
|May 4, 2019
PubMed
Abstract

Insights

Trichostatin A (TSA) reversed cigarette smoke (CS)-induced uterine damage by inhibiting histone deacetylase 1 and 2 (HDAC1/2). This treatment restored uterine structure and macro-autophagy, suggesting TSA as a potential therapy for reproductive issues caused by smoking.

Area of Science:

  • Reproductive Biology
  • Molecular Biology
  • Toxicology

Background:

  • Cigarette smoking (CS) is known to negatively impact reproductive health.
  • The specific roles of histone deacetylase 1 and 2 (HDAC1/2) in CS-induced uterine tissue changes and the therapeutic potential of HDAC inhibitors like trichostatin A (TSA) remain unexplored.

Purpose of the Study:

  • To investigate the involvement of HDAC1/2 in CS-induced uterine structural alterations.
  • To evaluate the therapeutic efficacy of TSA in mitigating CS-induced reproductive damage.

Main Methods:

  • Female mice were exposed to CS for 30 days, with TSA administered to a treatment group.
  • Uterine histomorphology, HDAC1/2 distribution, and key molecular markers of autophagy and signaling pathways (Beclin-1, LC3-II, p62, mTOR, IRS, FOXO1/3) were analyzed.

Main Results:

  • CS exposure led to decreased body weight, uterine thinning, and reduced cellularity, accompanied by HDAC1/2 activation.
  • TSA treatment effectively inhibited HDAC1/2, attenuated CS-induced weight loss, and restored uterine morphology.
  • TSA normalized macro-autophagy markers and modulated signaling pathways, including reducing phosphorylated mTOR and IRS.

Conclusions:

  • TSA effectively counteracted uterine histomorphological damage caused by CS exposure.
  • The therapeutic effects of TSA may be attributed to the resumption of macro-autophagy through HDAC1/2 inhibition.
Keywords:
Cigarette smokingMacro-autophagyTSAUterus

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