Androgen promotes oocyte development by upregulating gap junction intercellular communication activity in granulosa cells in mice

Background: Recent studies have highlighted the role of androgen in poor ovarian response (POR). However, the mechanisms by which androgen works, particularly in older POR patients, remain unclear. The study aimed to investigate the effects of androgen on granulosa cells and to explore the underlying mechanisms preliminarily.

Methods: Elderly female C57BL/6J mice were treated with various concentrations of dehydroepiandrosterone (DHEA) in vivo. Granulosa cells were exposed to different concentrations of testosterone (T), flutamide (an Androgen Receptor antagonist, AR antagonist), and GF109203X (a protein kinase C inhibitor, PKC Inhibitor) in vitro. Gap junction intercellular communication (GJIC) activity was analyzed using the scrape loading/dye transfer technique.

Results: DHEA treatment significantly increased serum DHEA, T, and anti-Müllerian hormone levels, as well as the number of oocytes harvested. Treatment with T within the physiological concentration range significantly increased GJIC activity. These effects of T were partially counteracted by flutamide or GF109203X.

Conclusions: Androgen may enhance GJIC activity in granulosa cells via the AR pathway and PKC signaling pathway, an effect associated with improved oocyte development in mice. The findings provide a theoretical basis for the use of androgen pretreatment to improve ovarian response in older POR patients.