Dataset Information

Obesity significantly alters the human sperm proteome, with implications for fertility

ABSTRACT: While obesity has links to poor semen parameters and reduced fertility, the causative links between obesity and male infertility are unclear, particularly on a molecular level. We investigated how obesity impacts the human sperm proteome, to further understand any implications for fertility. Sperm protein lysates from 5 healthy weight (BMI < 25) or obese (BMI>30) men were FASP digested, analysed by LC-MS/MS and quantitatively compared by label free quantification. Findings were confirmed for representative proteins by immunofluorescence staining. 2034 proteins were confidently identified, with 24 significantly less abundant (fold change <0.5) and 3 significantly more abundant (fold change >1.5)in sperm of obese men. These proteins were involved in a range of biological processes, including oxidative stress (GSS, NDUFS2, JAGN1, USP14, ADH5), inflammation (SUGT1, LTA4H), translation (EIF3F, EIF4A2, CSNK1G1), DNA damage repair (UBEA4) and sperm function (NAPA, RNPEP, BANF2). These results suggest that oxidative stress and inflammation are closely tied to reproductive dysfunction in obese men. These processes likely impact protein translation and folding during spermatogenesis, leading to poor sperm function and subfertility. The observation of these changes in normozoospermic men further suggests that traditional clinical semen assessment fails to detect important biological changes in spermatozoa which may compromise fertility.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Primary Cell, Sperm

DISEASE(S): Obesity

SUBMITTER: Taylor Pini

LAB HEAD: Taylor Pini

PROVIDER: PXD014849 | Pride | 2020-02-18

REPOSITORIES: Pride

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Obesity significantly alters the human sperm proteome, with potential implications for fertility.

Pini T T Parks J J Russ J J Dzieciatkowska M M Hansen K C KC Schoolcraft W B WB Katz-Jaffe M M

Journal of assisted reproduction and genetics 20200205 4

<h4>Purpose</h4>In men, obesity may lead to poor semen parameters and reduced fertility. However, the causative links between obesity and male infertility are not totally clear, particularly on a molecular level. As such, we investigated how obesity modifies the human sperm proteome, to elucidate any important implications for fertility.<h4>Methods</h4>Sperm protein lysates from 5 men per treatment, classified as a healthy weight (body mass index (BMI) ≤ 25 kg/m<sup>2</sup>) or obese (BMI ≥ 30 k ...[more]

PMID: 32026202

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Project description:<h4><strong>BACKGROUND: </strong>Semen quality is negatively correlated with male age and is mainly quantified by a routine semen analysis, which is descriptive and inconclusive. Sperm proteins or semen metabolites are used as the intermediate or end-products, reflecting changes in semen quality, and hold much promise as a new biomarker to predict fertility in advanced-aged males.</h4><h4><strong>OBJECTIVES: </strong>In this study, we sought to assess whether the semen metabolome and proteome of aged males can affect semen quality and serve as biomarkers for predicting semen quality.</h4><p><strong>MATERIALS AND METHODS: </strong>We retrospectively analyzed 12825 males that underwent semen routine analysis to understand the age-dependent changes in sperm quality. To identify the difference between aged and young adults, metabolomics (n=60) analyses of semen and proteomics (n=12) analyses of sperm were conducted. Finally, integrated machine learning of metabolomics was conducted to screen biomarkers to identify aging semen.</p><p><strong>RESULTS:</strong> We discovered that male age was positively correlated with sperm concentration as well as DNA fragmentation index(DFI), and negatively with progressive motile sperm count, total sperm count, sperm volume and progressive sperm motility. The differential metabolites were significantly enriched in various metabolic pathways, and four of these differential metabolites (Pipamperone, 2,2-Bis(hydroxymethyl)-2,2',2''-nitrilotriethanol, Arg-Pro and Triethyl phosphate) were utilized to establish a biomarker panel to identify aging semen. Proteomic analysis showed that differential proteins were significantly enriched in protein digestion and absorption and some energy-related pathways. An integrated analysis of the metabolome and proteome identified differential energy metabolism and oxidative stress-related proteins, which could explain the decreased motility and the increased DFI of aging sperm.</p><p><strong>DISCUSSION AND CONCLUSION:</strong> We provide compelling evidence that the changes in semen metabolome and sperm proteome are related to the decline of semen quality in aged males. Moreover, a biomarker panel based on four metabolites was established to identify aging semen.</p>

Dataset Information

Obesity significantly alters the human sperm proteome, with implications for fertility

Publications

Obesity significantly alters the human sperm proteome, with potential implications for fertility.

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