The impact of significant weight loss following bariatric surgery on the differential expression of phosphopeptides in human seminal fluid

During the last few decades, the global population has shown increased obesity rates. Obesity has been linked to declines in male reproductive capacity, suggesting a causal connection. However, standard fertility tests, such as semen analysis, often fail to predict reproductive success accurately because they do not assess molecular and functional sperm qualities. To address this, this pilot study explores the role of post-translational modifications, such as phosphorylation, as potential fertility markers. We studied six morbidly obese men scheduled for bariatric surgery; all of them were monitored before surgery and then 3 and 6 months afterward. Recruited patients showed statistically significant weight loss and improved hormonal profiles, including higher testosterone and SHBG levels; however, standard semen parameters changed little. Using Mass spectrometry, we evaluated the sperm proteome and phosphoproteome from control patients and patients before and 3 and 6 months after bariatric surgery. Sperm proteomics showed no differences across collection times; however, phosphoproteomics of seminal fluid revealed that 7 phosphopeptides differed significantly across collection times. These post-translational modifications were observed in proteins such as semenogelin-1, semenogelin-2, mucin-6, and AKAP-3 and AKAP-4. Interestingly, these proteins are critical in sperm capacitation, a vital process for fertilization, suggesting a potential molecular mechanism for the reduced reproductive function in obese patients. These results suggest that seminal fluid, rather than sperm alone, may be crucial in mediating changes in fertility associated with obesity and weight loss. Although our results come from a small patient population, the findings highlight the shortcomings of conventional semen analysis and support the potential use of proteomic biomarkers to better understand and assess male fertility amid obesity and metabolic changes.