Effect of intraperitoneal docetaxel on ovarian function in mice.

Taxanes are important chemotherapeutic agents used to manage breast cancer and gynaecological malignancies. However, ovarian toxicity induced by the taxane docetaxel (DOC) is of great concern. We investigated DOC-induced toxicity in the ovaries of female CD1 strain mice. The mice were divided into control (saline), DOC-5 (5 mg/kg DOC), and DOC-10 (10 mg/kg DOC) groups and administered saline or DOC on the first day of the study and two weeks later. Two weeks after the second dose, the ovaries were removed for analysis after inducing superovulation. Ovary weight, the number of secondary follicles, and the total number of follicles were reduced after DOC administration. Additionally, the expression levels of caspase-3 and the pro-apoptotic protein Bcl-2 interacting mediator of cell death (BIM) increased. Our findings suggest that high-dose DOC induces damage to growing follicles; however, it may not affect primordial follicles.Impact statementWhat is already known on this subject? Docetaxel (DOC) is one of the most effective chemotherapeutic agents used to manage various cancers. Some in-vitro studies have examined paclitaxel-induced ovarian toxicity; however, limited research on DOC is available.What do the results of this study add? We investigated DOC-induced ovarian toxicity in female CD1 strain mice at 5 mg/kg and 10 mg/kg. We found that DOC reduced ovary weight, the number of secondary follicles, and the total number of follicles, with the higher dose having a higher effect.What are the implications of these findings for clinical practice and/or further research? We believe that our study makes a significant contribution to the knowledge about the effect of DOC on ovarian function.

Mental stress promotes the proliferation of endometriotic lesions in mice.

Endometriosis is a condition in which tissue similar to the womb lining begins to grow in other sites, such as the ovaries or fallopian tubes. Endometriosis can cause pelvic pain, adhesion formation, and infertility. Here, we investigated the relationship between deterioration of endometriosis and inflammation of intraperitoneal adipose tissue in mice. We created a mouse model of endometriosis, then subjected these mice to stress loading. In the experimental mice, we measured protein expression levels of prostaglandin-E2, monocyte chemoattractant protein-1, and tumor necrosis factor-α using ELISA kits. We used quantitative real-time polymerase chain reaction to measure mRNA expression levels of inflammation-related enzymes and cytokines in lesions and adipose tissues. This study sugest that endometriotic lesions may progress in the presence of psychological stress in the presence of endometriosis. In addition, inflammation of the adipose tissue around the uterus may be involved in the development of endometriosis. However, this needs further consideration. Reducing or avoiding stress as much as possible may prevent the progression of endometriosis.

Intraperitoneal administration of activin A promotes development of endometriotic lesions in a mouse model of endometriosis.

PURPOSE: This study aimed to investigate the effect of intraperitoneal administration of activin on the occurrence of endometriosis using a mouse model of endometriosis. METHODS: A mouse model of endometriosis was prepared by intraperitoneally administering endometrial tissue and blood collected from donor mice to C57BL/6J 7-8- week-old recipient mice. A total of 400 µg of activin A was intraperitoneally administered to model mice in the activin group for 5 days. Intraperitoneal endometriotic lesions were confirmed macroscopically and IL-6 and TNF-α levels in washed ascites were measured by ELISA. RESULTS: Endometriotic lesions were observed in all mice. In the activin group, the maximum diameter of endometriotic lesions was significantly larger than that in control group (4.7?1.3 vs 2.9?0.9 mm, p?0.01). The total area of the lesion was also significantly higher in the activin group than in the control group (21.1?9.9 vs 8.8?5.4 mm2,p?0.01). Furthermore, IL-6 and TNF-α levels in ascites were significantly higher in the activin group than in the control group (IL-6 : 85.8?15.3 vs 75.1?19.3 pg/ml, p?0.05 ; TNF-α : 629.8?15.4 vs 605.9?11.4 pg/ml, p?0.05). CONCLUSION: Activin promotes occurrence of endometriosis. Inflammatory cytokines are also elevated by activin administration,suggesting that they may contribute to progression of endometriosis J. Med. Invest. 66 : 123-127, February, 2019.

Lipopolysaccharide promotes early endometrial-peritoneal interactions in a mouse model of endometriosis.

PURPOSE: The aims of this study were to clarify the effects of lipopolysaccharide (LPS) on the early development of endometriosis and on the production of cytokines and chemokines in the murine peritoneal cavity. METHODS: Endometriotic lesions were induced in C57BL/6J adult female mice by intraperitoneal injection of endometrial fragments plus blood or endometrial fragments plus blood with LPS. On day 7, endometriotic lesions were assessed by gross and microscopic evaluations. Time-dependent changes in the secretion of TNF-α,IL-6,and CXCL2/MIP-2 in peritoneal lavage fluid after the intraperitoneal injection of LPS (50 µg/body) were measured by their respective enzyme-linked immunosorbent assays. RESULTS: The areas of endometriotic lesions in the LPS group (10.8 8.6 mm2) were significantly larger than those in the control group (3.1 3.7 mm2).The levels of TNF-α and IL-6 peaked within 2 hours and the level of MIP-2 reached a maximum on day 1 after the injection of LPS. CONCLUSIONS: LPS promotes development of the early stages of murine endometriotic lesions. J. Med. Invest. 66 : 70-74, February, 2019.