A tumor necrosis factor α inhibitor reduces the embryotoxic effects of endometriotic peritoneal fluid
The abundant TNF-a in the peritoneal fluid of women with endometriosis plays an important role in endometriosis-induced embryotoxicity. The TNF-a inhibitors could potentially be used to treat endometriosis-related infertility.
Yi-Jen Chen, M.D., Ph.D., Hua-Hsi Wu, M.D., Wan-Ting Liau, Chang-Youh Tsai, M.D., Ph.D., Hsiao-Wen Tsai, M.D., Ming-Shyen Yen, M.D., Kuan-Chong Chao, M.D., Yen-Jen Sung, M.D., Ph.D., Hsin-Yang Li, M.D., Ph.D.
Volume 100, Issue 5, Pages 1476-1485.e5, November 2013
To determine whether a tumor necrosis factor-α (TNF-α) inhibitor can reduce the embryotoxicity of the peritoneal fluid (PF) of women with endometriosis.
Experimental clinical study.
Twelve women with chocolate cysts and 12 control women without endometriosis.
Main Outcome Measure(s):
We collected the PF from patients with chocolate cysts (CH-PF) and patients without endometriosis (N-PF) during laparoscopic surgery. For the in vitro studies, development and apoptosis were evaluated in two-cell stage mouse embryos after incubation with CH-PF and N-PF, with or without a TNF-α inhibitor.
We found that CH-PF significantly decreased the rate of blastocyst development and increased the percentage of apoptotic cells in the embryos. Cytokine assays showed that the concentrations of several cytokines, including TNF-α, were higher in embryos incubated with CH-PF than in those incubated with N-PF. Furthermore, the treatment of embryos with TNF-α retarded development and induced apoptosis. Important, adalimumab, a TNF-α inhibitor, effectively abrogated the embryotoxicity that was induced by CH-PF.
These data collectively highlight the crucial role of TNF-α in CH-PF-induced embryotoxicity and suggest that TNF-α inhibitors may be potential therapeutic agents for treating endometriosis-induced infertility.