Perimenopausal and Menopausal Mammary Glands In A 4-Vinylcyclohexene Diepoxide Mouse Model

Area of Science:

• Reproductive biology
• Endocrinology
• Cancer research

Background:

• Menopause and perimenopause are critical windows for breast cancer development.
• Traditional ovariectomy models do not accurately reflect natural menopause.
• A physiologically relevant model is needed to study hormonal changes and breast carcinogenesis.

Purpose of the Study:

• To characterize a novel 4-vinylcyclohexene diepoxide (VCD)-induced mouse model for perimenopausal and menopausal mammary gland states.
• To investigate the effects of polybrominated diphenyl ethers (PBDEs) on the mammary gland during menopausal transition.
• To assess PBDEs' impact on ductal reorganization and cellular changes in the mammary gland.

Main Methods:

• Induction of perimenopausal and menopausal states using VCD in mice.
• Exposure to PBDEs via chronic low-dose (environmental) and subacute high-dose (experimental) modes.
• Analysis of mammary gland morphology, hormonal responsiveness, and transcriptomic changes using single-cell RNA sequencing.

Main Results:

• The VCD model successfully replicated perimenopausal and menopausal mammary gland characteristics.
• PBDE exposure did not alter macroscopic ductal reorganization during menopausal transition.
• Experimental PBDE exposure induced specific transcriptomic changes in non-epithelial cells, such as fibroblast Errfi1 upregulation, in post-menopausal glands.

Conclusions:

• The VCD mouse model provides a valuable tool for studying breast cancer during menopausal transition.
• PBDEs may influence the post-menopausal mammary gland, particularly non-epithelial compartments, despite not affecting ductal structure.
• Further research is warranted to understand the long-term implications of PBDEs on mammary gland health during and after menopause.