CACNA2D1 promotes ovulation by regulating ovarian immune cell infiltration

Area of Science:

• Reproductive biology and immunology
• Molecular and cellular mechanisms of ovulation

Background:

• Previous single-cell transcriptome analysis identified CACNA2D1's potential role in immune cell infiltration during goat ovulation.
• The precise function of CACNA2D1 in the ovulation process remained to be elucidated.

Purpose of the Study:

• To investigate the functional role of CACNA2D1 in the complex process of ovulation.
• To determine CACNA2D1's involvement in ovarian immune cell dynamics and ovulatory efficiency.

Main Methods:

• Pharmacological inhibition of CACNA2D1-associated signaling in a mouse ovulation model.
• In vitro studies involving CACNA2D1 knockdown and overexpression in ovarian granulosa cells.
• Assessment of immune cell infiltration, ovulatory output, transcriptomic changes, chemokine production, calcium signaling, CaMKII activation, cell proliferation, and macrophage migration.

Main Results:

• CACNA2D1 expression increased during the periovulatory period.
• Inhibition of CACNA2D1 signaling reduced ovarian immune cell infiltration (especially macrophages) and decreased ovulatory output.
• CACNA2D1 knockdown in granulosa cells impaired calcium signaling, suppressed chemokine production (IL6, CCL2, CXCL12), and reduced macrophage migration.

Conclusions:

• CACNA2D1 acts as a periovulatory regulator in granulosa cells, mediating calcium-dependent chemokine production and macrophage recruitment.
• Findings offer insights into ovarian immune remodeling during ovulation and potential targets for fertility regulation in livestock.