Effects of STAT Inhibitors in Mouse Models of Endometriosis

• Published in: Reproductive sciences (Thousand Oaks, Calif.) Calif.), 2023-08, Vol.30 (8), p.2449-2456
• Main Authors: Inui, Hiroaki, Kawakita, Takako, Murayama, Misaki, Nakagawa, Tomotaka, Sasada, Hikari, Shinohara, Ayaka, Aragaki, Ryousuke, Kagawa, Tomohiro, Kadota, Yuri, Kato, Takeshi, Nishimura, Masato, Iwasa, Takeshi
• Format: Article
• Language: English
• Subjects: Animals; Disease Models, Animal; Embryology; Endometriosis - metabolism; Endometriosis: Original Article; Female; Humans; Interleukin-6 - metabolism; Medicine; Medicine & Public Health; Mice; Obstetrics/Perinatology/Midwifery; Reproductive Medicine; RNA, Messenger; Signal Transduction; STAT3 Transcription Factor - metabolism
• ISSN: 1933-7191; 1933-7205
• DOI: 10.1007/s43032-023-01202-2

The signal transducer and activator of transcription (STAT) pathway, which regulates cell proliferation and immunity, has been implicated in chronic inflammatory diseases such as rheumatoid arthritis. However, few reports have described the effects of STAT inhibitors on endometriosis, another chronic inflammatory disease. Here, we investigated the intraperitoneal microenvironment and the effects of a STAT inhibitor in a mouse model of endometriosis. In the treatment group, a STAT3 inhibitor (Stattic®, 80 mg/kg) was orally administered three times per week; control animals received orally dosed phosphate-buffered saline. Endometriosis-like lesions and peritoneal lavage fluid were collected before and 1, 2, and 3 weeks after STAT3 inhibitor administration was initiated. The lesion area was significantly increased in both groups after the first week. However, in the treatment group, the lesion areas were significantly reduced at weeks 2 and 3 compared with week 1. Transforming growth factor (TGF)-β messenger RNA (mRNA) levels in ascites cells were significantly lower at weeks 1 and 2 than at week 0. Interleukin (IL)-6 mRNA levels were significantly higher at week 1 than at week 0 but were significantly lower at weeks 2 and 3 than at week 1. Thus, STAT inhibitors appeared to reduce the extent of endometriosis in this mouse model, and may also inhibit the IL-6 signaling pathway and reduce TGF-β levels. This study suggests that STAT inhibitors warrant further exploration for use in the treatment of endometriosis.