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. 2020 Apr;37(4):777-787.
doi: 10.1007/s10815-020-01707-8. Epub 2020 Feb 5.

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

T Pini  1 , J Parks  2 , J Russ  2 , M Dzieciatkowska  3 , K C Hansen  3 , W B Schoolcraft  2 , M Katz-Jaffe  2
Affiliations

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

T Pini et al. J Assist Reprod Genet. 2020 Apr.

Abstract

Purpose: 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.

Methods: Sperm protein lysates from 5 men per treatment, classified as a healthy weight (body mass index (BMI) ≤ 25 kg/m2) or obese (BMI ≥ 30 kg/m2), were FASP digested, submitted to liquid chromatography tandem mass spectrometry, and compared by label-free quantification. Findings were confirmed for several proteins by qualitative immunofluorescence and a quantitative protein immunoassay.

Results: A total of 2034 proteins were confidently identified, with 24 proteins being significantly (p < 0.05) less abundant (fold change < 0.05) in the spermatozoa of obese men and 3 being more abundant (fold change > 1.5) compared with healthy weight controls. Proteins with altered abundance were involved in a variety 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).

Conclusion: 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 obese men with no overt andrological diagnosis further suggests that traditional clinical semen assessments fail to detect important biochemical changes in spermatozoa which may compromise fertility.

Keywords: Fertility; LC-MS/MS; Obesity; Proteome; Reproduction; Spermatozoa.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Representative images of qualitative immunofluorescence. Spermatozoa from control (BMI < 25 kg/m2) or obese (BMI > 30 kg/m2) men were incubated with antibodies against GSS or NDUFS2 and a FITC-conjugated secondary antibody. DAPI staining was included to identify all spermatozoa. A secondary antibody only control was included to assess non-specific binding
Fig. 2
Fig. 2
Obesity creates systemic inflammation and oxidative stress, two closely inter-related processes. When occurring locally in the testes, these processes may impact spermatogenesis and mature sperm function either directly, or indirectly, via the formation of protein/reactive byproduct adducts and subsequent protein dysfunction
See this image and copyright information in PMC

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