Transcription Factor Gene Pea3 Regulates Erectile Function in Mice

Background: Male mice with homozygous loss of function mutations of the ETS transcription factor gene Pea3 (Pea3 null) are infertile due to their inability to deposit semen plugs, however the specific deficits in male sexual behaviors that drive this phenotype are unknown. Aim: To investigate the regulatory role of the Pea3 gene in organizing gross sexual behaviors and erectile functioning during active copulation. Methods: The copulatory behavior of male mice (Pea3 null and control) with hormonally primed ovariectomized females was monitored via high-speed and high-resolution digital videography to assess for differences in female-directed social behaviors, gross sexual behaviors (mounting, thrusting), and erectile and ejaculatory function. Outcomes: Pea3 null male mice have dramatically reduced erectile function during sexual intercourse, however other aspects of male sexual behaviors are largely intact. Results: Pea3 null male mice exhibit greatly reduced erectile function, with 44% of males displaying no visible erections during mounting behaviors, and none achieving sustained erections. As such, Pea3 null males are incapable of intromission, and semen plug deposition, despite displaying largely normal female-directed social behaviors, mounting behaviors, and ejaculatory grasping behavior. Additionally, the coordination of the timing of thrusting trains is impaired in Pea3 null males. Clinical Implications: The identification of the transcription factor Pea3 in regulating erectile function in mice may provide a useful target for understanding the genetics of male sexual dysfunction in human patients. Strengths and Limitations: High-speed and high-resolution videography allows for a detailed analysis of male sexual behaviors and erectile functioning in Pea3 null and control mice. How disruption of the Pea3 gene translates to erectile dysfunction is still unknown. Conclusion: The transcription factor gene Pea3 regulates the ability to achieve and maintain erections in male mice.