Cortisol modulates Ca²⁺ signaling and acrosome reaction in human sperm

Stress and elevated cortisol levels have negative effects on fertility, although there is controversy about the effect of cortisol on human sperm. One study reported that hydrocortisone (HC), the synthetic form of cortisol, does not activate CatSper channel but is able to inhibit its activation by progesterone (Pg). However, subsequent reports showed that HC has an agonist effect on CatSper, producing intracellular Ca²⁺ ([Ca²⁺ ]_i ) increases. These studies were performed using only electrophysiological techniques and fluorometric measurements of Ca²⁺ . Therefore, it is important to evaluate the effects of different HC concentrations on human sperm physiology using other approaches and techniques.

To analyze the effects of different HC concentrations on human sperm physiology and to evaluate the association of perceived stress, anxiety and depression with acrosome reaction (AR), and semen quality.

In capacitated human sperm, we tested the effects of HC on [Ca²⁺ ]_i mobilization and AR. Furthermore, the perceived stress and symptoms of anxiety and depression were evaluated with standardized psychometric tests.

HC induces a low increase in [Ca²⁺ ]_i compared to Pg response while, at higher concentrations, HC inhibits the Pg-induced Ca²⁺ response. Also, low concentrations of HC induce AR and when co-incubating it with Pg, the percentages of AR are decreased. Finally, the anxiety symptoms are negatively correlated with Pg induced AR and semen quality.

HC has an agonist effect on [Ca²⁺ ]_i mobilization and AR. However, our data also suggest that HC may compete for the binding site of Pg. Additionally, the association between anxiety and decreased AR could be explained by high cortisol levels.

Our data showed that HC interferes with the Pg action. Therefore, the negative correlation between anxiety symptoms and Pg-induced AR is due to the accompanying high cortisol levels of this condition and its competitive action with Pg.