Obesity or Overweight, a Chronic Inflammatory Status in Male Reproductive System, Leads to Mice and Human Subfertility

Abstract

Obesity is frequently accompanied with chronic inflammation over the whole body and is always associated with symptoms that include those arising from metabolic and vascular alterations. On the other hand, the chronic inflammatory status in the male genital tract may directly impair spermatogenesis and is even associated with male subfertility. However, it is still unclear if the chronic inflammation induced by obesity damages spermatogenesis in the male genital tract. To address this question, we used a high fat diet (HFD) induced obese mouse model and recruited obese patients from the clinic. We detected increased levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and NOD-like receptor family pyrin domain containing-3 (NLRP3) in genital tract tissues including testis, epididymis, seminal vesicle, prostate, and serum from obese mice. Meanwhile, the levels of immunoglobulin G (IgG) and corticosterone were significantly higher than those in the control group in serum. Moreover, signal factors regulated by TNF-α, i.e., p38, nuclear factor-κB (NF-κB), Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and their phosphorylated status, and inflammasome protein NLRP3 were expressed at higher levels in the testis. For overweight and obese male patients, the increased levels of TNF-α and IL-6 were also observed in their seminal plasma. Furthermore, there was a positive correlation between the TNF-α and IL-6 levels and BMI whereas they were inversely correlated with the sperm concentration and motility. In conclusion, impairment of male fertility may stem from a chronic inflammatory status in the male genital tract of obese individuals.

Protective Role of Eurycoma longifolia Jack Root Extract Against High-Fat Diet Induced Testicular Damage in Sprague-Dawley Rats

“…21 The present histopathological result of HFD feeding is comparable to earlier studies of HFD-induced testicular injury; the HFD fed rats' revealed degeneration in testicular morphology, characterized as atrophied seminiferous tubules, disruption in spermatogenesis and vacuolation of germinal epithelium, this is contestant with previous studies who demonstrated atrophied seminiferous epithelia, coalescence between spermatogenic cells and impaired and loosely organized Sertoli cells in mice fed HFD. 22 Atrophied seminiferous tubuli were also observed in HFD treated rats associated disconnection of the degenerated STs from the interstitial wall with increased area of the connective tissue and remarkable apoptotic activity in Leydig and Sertoli cells. 9 Vacuolar alterations in seminiferous tubules, spermatogenic cell dysfunction, and increased apoptosis of spermatogenic cells in testicular tissue was also observed in HFD treated rats.…”

Effect of alcohol on chronic pelvic pain and prostatic inflammation in a mouse model of experimental autoimmune prostatitis

“…The past decade has witnessed many studies, which suggested that the malfunction of NLRP3 inflammasome is a potent trigger of a series of autoinflammatory and autoimmune diseases, including gout, rheumatoid arthritis, and lupus . Moreover, NLRP3 inflammasome has been reported to participate in the chronic inflammation status in the prostate …”

“…12 Moreover, NLRP3 inflammasome has been reported to participate in the chronic inflammation status in the prostate. [13][14][15] Alcohol consumption is widespread all over the world. Alcohol use disorders extensively exist globally.…”

The Role of Diet and Weight Loss in Improving Secondary Hypogonadism in Men with Obesity with or without Type 2 Diabetes Mellitus

“…Also, in the testis, TNF-α, IL-1β, and IL-6 were associated with a dose-dependent decline in steroidogenesis in TM3 Leydig cells [64]. Furthermore, in rat models of diet-induced obesity, high levels of TNF-α, IL-1β, and IL-6 were associated with the disruption of testicular morphology, with a reduction in seminiferous tubule diameter, epithelial and germ cell atrophy and apoptosis, abnormal adhesions between Sertoli and spermatogenic cells and the blood-testis barrier disassembly [65]. On the other hand, even if IL-8 exerts a stimulating effect on TM3 Leydig cell growth, it appears to minimally affect T production and blood concentrations [64].…”