Leptin action on ARC-PVN neural circuit regulates ejaculation behavior by altering sympathetic neuroplasticity

Background: Although some studies have revealed the close relationship between leptin and premature ejaculation in clinical practice, whether and how leptin participates in the regulation of ejaculatory behaviors are still unknown.

Objective: To explore the role of leptin on ejaculatory behaviors and its underlying mechanism.

Materials and methods: Copulation behavior tests were performed after acute and chronic leptin administration at peripheral and central levels. To compare changes in sympathetic nervous system activity, lumbar sympathetic nervous activity, serum noradrenaline levels, and the distribution of sympathetic fibers in vas deferens and seminal vesicles were analyzed. Construction of virus vector, immunohistochemistry, and optogenetics techniques were used to explore the neural circuit mechanism. The density of dendritic spines in parvocellular region of paraventricular nucleus was measured by Golgi staining.

Results: Acute administration of leptin had no effect on ejaculation behavior in male mice. However, both mount latency and ejaculation latency were significantly shortened, even if serum leptin decreased to normal level, after chronic administration of leptin at peripheral or central level. Additionally, sympathetic fibers in vas deferens and seminal vesicles obviously increased, in which arcuate nucleus‒paraventricular nucleus circuit and glutamatergic neurons in paraventricular nucleus played an important role. Dendritic spine density in parvocellular region increased after chronic leptin administration.

Discussion and conclusion: The role of leptin in regulating ejaculation behavior was chronic, not acute, in which leptin chronically modulated sympathetic neuroplasticity via arcuate nucleus‒paraventricular nucleus circuit and glutamatergic neurons in paraventricular nucleus and promoted ejaculatory behaviors. Increased dendritic spine density in parvocellular region of paraventricular nucleus may be involved as well.