Bisphenol S enhances gap junction intercellular communication in ovarian theca cells

Area of Science:

• Reproductive Biology
• Endocrinology
• Cellular Signaling

Background:

• Gap junction intercellular communication (GJIC) is crucial for ovarian function and regulated during follicular development.
• Theca cells provide essential support to antral follicles, and their GJIC is vital for signaling molecule transport.
• Hormones and endocrine-disrupting chemicals (EDCs) can alter GJIC, raising concerns about reproductive health.

Purpose of the Study:

• To investigate the effects of five common EDCs (BPA, BPS, BPF, PFOS, TPT) on theca cell GJIC.
• To test the hypothesis that these EDCs inhibit theca cell GJIC at environmentally relevant concentrations.
• To explore the signaling pathways involved in any observed modulation of GJIC.

Main Methods:

• Scrape loading/dye transfer assay to measure GJIC in primary ovine theca cells.
• Treatment with five common EDCs at various concentrations and time points.
• Inhibition of signaling pathways (Phospholipase C, MAPK) to elucidate mechanisms.
• Validation of findings in primary human theca cells.

Main Results:

• Bisphenol S (BPS) significantly enhanced GJIC in ovine theca cells in a dose- and time-dependent manner.
• No other tested EDC (BPA, BPF, PFOS, TPT) affected theca cell GJIC.
• BPS-induced enhancement of GJIC was attenuated by Phospholipase C and MAPK inhibitors.
• Human theca cells showed a similar BPS-induced increase in GJIC, also attenuated by MAPK inhibition.

Conclusions:

• BPS uniquely enhances GJIC in both ovine and human theca cells, suggesting a conserved mechanism.
• The enhancement of GJIC by BPS involves MAPK signaling pathways.
• Upregulated theca cell GJIC may lead to theca cell hyperplasia or disrupt ovulation, potentially affecting fertility.
• Further research is needed to correlate in vitro findings with in vivo effects on follicle development and fertility.