Estrogen Signaling During Abrupt Involution Leads to Long-Term Metabolic Dysfunction Similar to Estrogen Receptor...

Area of Science:

• Reproductive biology
• Oncology
• Metabolic research

Background:

• Epidemiological studies link reduced breastfeeding to increased breast cancer risk.
• Mammary gland involution post-birth differs between abrupt involution (AI) and gradual involution (GI) based on breastfeeding duration.
• AI is associated with precancerous changes, but its metabolic impact remains unclear.

Purpose of the Study:

• To investigate the metabolic effects of abrupt involution (AI) in the mammary gland.
• To explore the potential link between AI-induced metabolic changes and breast cancer development.

Main Methods:

• Mouse models were used to simulate AI (pups removed day 7) and GI (pups removed days 28-31).
• Mammary glands were analyzed transcriptionally, functionally, and via metabolite analysis at multiple postpartum time points.
• Tamoxifen treatment was administered to a subset of AI mice to assess its impact on metabolic pathways.

Main Results:

• Early differences in metabolic pathways were observed between AI and GI glands.
• AI glands showed altered estrogen signaling, glucose metabolism, and adipogenesis compared to GI glands.
• Long-term AI induced mitochondrial dysfunction and metabolic changes resembling those in estrogen receptor-negative breast cancer.

Conclusions:

• Differences in adipocyte repopulation and estrogen signaling may drive early metabolic changes in AI glands.
• The long-term metabolic consequences of AI mirror those observed in breast cancer, suggesting a potential causal link.