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Peer-reviewedCC BYFrontiers in endocrinology

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

  1. 1Department of Obstetrics, Gynecology and Reproductive Science, Division of Reproductive Endocrinology and Infertility, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
  2. 2Department of OBGYN and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, United States.
  3. 3Department of Urology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.

Abstract

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.

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BibTeX
@article{vitez2026impact,
  title = {{The impact of significant weight loss following bariatric surgery on the differential expression of phosphopeptides in human seminal fluid.}},
  author = {Sally F Vitez and Odei Barreñada and Kathleen Hwang and Miguel Angel Brieño-Enríquez},
  journal = {Frontiers in endocrinology},
  year = {2026},
  month = oct,
  doi = {10.3389/fendo.2026.1907857},
  url = {https://europepmc.org/article/MED/42910009},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - The impact of significant weight loss following bariatric surgery on the differential expression of phosphopeptides in human seminal fluid.
AU  - Sally F Vitez
AU  - Odei Barreñada
AU  - Kathleen Hwang
AU  - Miguel Angel Brieño-Enríquez
PY  - 2026
DA  - 2026/10/07
JO  - Frontiers in endocrinology
DO  - 10.3389/fendo.2026.1907857
UR  - https://europepmc.org/article/MED/42910009
AB  - 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.
SN  - 1664-2392
ER  -