Antiestrogenic property of 9,9-bis[4-(2-hydroxyethoxy)phenyl]fluorene (BPEF) and its effects on female development in CD-1 mice

Abstract

Identifying chemicals with endocrine disrupting properties linked to disease outcomes is a key concern, as stated in the WHO-UNEP 2012 report on endocrine-disrupting chemicals. The chemical 9,9-bis[4-(2-hydroxyethoxy)phenyl]fluorene (BPEF) is widely and increasingly applied in synthesizing fluorene-based cardo polymers with superior optical, thermal and mechanical properties for various uses. However, little toxicological information is available regarding its safety. Here, we studied the endocrine disrupting property of BPEF by multiple toxicological tools and investigated its effects on female development in adolescent mice. Using the yeast two-hybrid bioassay, BPEF showed strong antiestrogenicity which was similar to that of tamoxifen, an effective antiestrogenic drug. In adolescent CD-1 mice, BPEF significantly decreased the uterine weight at relatively low doses and induced marked endometrial atrophy. Immunohistochemical staining and transcriptome analyses of the mice uteri revealed that BPEF could repressed the expressions of estrogen-responsive genes. Molecular simulation indicated that BPEF could be docked into the antagonist pocket of human estrogen receptor α, and the formation of hydrogen bonds and hydrophobic interactions between BPEF and the active site of receptor maintained their strong binding. All of the data demonstrated that BPEF possessed strong antiestrogenic property and might disrupt female development, suggesting it should be avoided in making products that might directly expose to people, particularly immature women.