Effects of Hydrogen Gas Inhalation on Endometriosis in Rats

Reprod Sci. 2017 Feb;24(2):324-331. doi: 10.1177/1933719116655622. Epub 2016 Sep 27.


Objective: Oxidative stress is generated during the pathophysiology of endometriosis (EMT). Hydrogen (H2) has been demonstrated as a gas antioxidant. The aim of the present study is to evaluate the protective effect of H2 on EMT in rats.

Study design: Sprague Dawley rats with surgically induced EMT were randomly received the inhalation of 67% H2-33% oxygen (O2) mixture (1 h/d, 4 weeks) immediately after the EMT surgery or 4 weeks after the operation. The mixture of 67% N2-33% O2 was also used to exclude the possible influence of the increased O2. Eight weeks after the operation, the endometrial tissues were weighted and analyzed using histology, immunohistochemistry, and real-time polymerase chain reaction. Several antioxidant enzymes and malondialdehyde were also measured in serum and tissue. The estrous cycles were monitored for H2 safety.

Results: The results showed that both profiles of high-dose H2 breathing reduced the size of the endometrial explants, inhibited cell proliferation, improved superoxide dismutase, glutathione peroxidase, malondialdehyde, and catalase activities, and regulated the expression of matrix metalloproteinase 9 and cyclooxygenase 2. However, inhalation of the same dose of nitrogen failed to show the protection. High-dose H2 breathing did not change the normal estrous cyclicity.

Conclusion: These results suggest that 67% H2-33% O2 breathing has a beneficial effect on EMT model rats, and inhalation of a high dose of H2 could be a potential method applied in clinical practice.

Keywords: antioxidative; endometriosis; hydrogen; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Animals
  • Disease
  • Disease Models, Animal
  • Endometriosis / drug therapy*
  • Endometriosis / metabolism
  • Endometriosis / pathology
  • Estrous Cycle / metabolism
  • Female
  • Hydrogen / administration & dosage
  • Hydrogen / therapeutic use*
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Sprague-Dawley


  • Malondialdehyde
  • Hydrogen