Leptin Dysfunction Implicated Further in Epididymitis and Male Subfertility

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Leptin dysfunction implicated further in epididymitis and male subfertility

Leptin is upregulated in epididymitis and promotes apoptosis and IL-1β production in epididymal epithelial cells by activating the NLRP3 inflammasome

In this study, patients with chronic epididymitis, rat models of epididymitis and an in vitro model was used to investigate the role of leptin in epididymitis, and its effect on inflammatory cytokine IL-1β and NLRP3 inflammasome.

Sixty three males with chronic epididymitis and 96 males diagnosed with male infertility but without chronic epididymitis, and other possible confounding factors, were included in this study to measure leptin levels in semen and seminal plasma.

Initial analysis found that serum leptin levels were significantly higher in the chronic epididymitis group (6.78 ±0.16) compared to the control group (6.24 ±0.10). Similarly seminal plasma levels of leptin was also significantly higher in chronic epididymitis patients (3.76 ±0.25) compared to the control group (1.77 ±0.16).

Progressive sperm motility was negatively associated with seminal plasma levels of leptin, meaning high levels of leptin correlated with a decrease in sperm motility. Interestingly no association was found between leptin levels and age, BMI or duration of infertility.

Lipopolysaccharide which is known to increase leptin levels in serum was administered to epididymitis rat models. As predicted leptin and leptin receptor expression was significantly increased in the epidydimal epithelium 12 to 72 hours after lipopolysaccharide administration.

In vitro model analysis found that leptin decreased cell viability and increased cell death via capase-3, capase-9 and Poly(ADP-ribose) polymerase. Similarly mRNA and protein levels of inflammatory cytokine IL-1β was enhanced along with IL-1β activator NLRP3.

Lastly using an NLRP3 inhibitor (MCC950) significantly reduced the effects of leptin or lipopolysaccharide on NLRP3, ASC, IL-1β and caspase-1.


In this study, of males with chronic epididymitis, a significant decrease in sperm motility and not sperm count was observed. Interestingly this decrease in progressive sperm motility correlated significantly with a linear increase in the leptin levels of males with epididymitis.


  1. Use of rat model tissue samples instead of human
  2. IL-1β production is not solely dependent on NLRP3
  3. Larger studies required to confirm these initial findings

Similar studies

Khodamoradi K, et al. (2020). The role of leptin and obesity on male infertility. https://doi.org/10.1097/MOU.0000000000000762

Wang H, et al. (2014). Seminal plasma leptin and spermatozoon apoptosis in patients with varicocele and leucocytospermia. https://doi.org/10.1111/and.12313


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