Proteomic profiling identifies circulating soluble MCAM/CD146 as a candidate biomarker for abnormal semen parameters in male infertility

Abstract

Background

A growing body of evidence suggests that male infertility is a precursor to future health problems. This study aimed to develop a unique circulating biomarker that could contribute to the diagnosis of male infertility.

Materials and methods

The study included 114 adult male participants aged 20–50 years who underwent sperm collection for in vitro fertilization and embryo transfer at Nagoya University Hospital, Gifu University Hospital, and Misao Ladies Hospital.

Results

Circulating VEGF-A and sFlt-1 levels did not differ significantly between men with normal and abnormal semen parameters. In contrast, proteomic analysis identified VEGFR1/2-related proteins associated with sperm motility, among which soluble MCAM/CD146 was significantly elevated in participants with abnormal semen parameters (84.0 [20.9–183.8] pg/mL vs 352.7 [115.8–1236.3] pg/mL, p < 0.0001), and in similar those with reduced sperm motility (106.5 [25.1–282.6] pg/mL vs 352.7 [125.5–1133.4] pg/mL, p < 0.0001). Receiver operating characteristic analysis demonstrated the diagnostic potential of soluble MCAM/CD146, with an area under the curve of 0.787, 66.7% sensitivity, and 78.6% specificity at the optimal threshold, supporting its role as a candidate biomarker for male infertility.

Conclusions

Circulating soluble MCAM/CD146 may represent a potential biomarker associated with abnormal semen parameters.

Keywords

Angiogenic factor male infertility semen parameter circulating biomarker

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References

Zegers-Hochschild

Adamson

de Mouzon

, et al. International Committee for monitoring assisted reproductive technology (ICMART) and the world health organization (WHO) revised glossary of ART terminology, 2009. Fertil Steril 2009; 92(5): 1520–1524. https://doi.org/10.1016/j.fertnstert.2009.09.009

Practice Committee of the American Society for Reproductive M . Diagnostic evaluation of the infertile Male: a committee opinion. Fertil Steril 2015; 103(3): e18–e25.

Mazzilli

Rucci

Vaiarelli

, et al. Male factor infertility and assisted reproductive technologies: indications, minimum access criteria and outcomes. J Endocrinol Investig 2023; 46(6): 1079–1085. https://doi.org/10.1007/s40618-022-02000-4

Ferrara

. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 2004; 25(4): 581–611. https://doi.org/10.1210/er.2003-0027

Obermair

Obruca

Pohl

, et al. Vascular endothelial growth factor and its receptors in male fertility. Fertil Steril 1999; 72(2): 269–275. https://doi.org/10.1016/s0015-0282(99)00234-4

Caires

de Avila

Cupp

, et al. VEGFA family isoforms regulate spermatogonial stem cell homeostasis in vivo. Endocrinology 2012; 153(2): 887–900. https://doi.org/10.1210/en.2011-1323

Iyibozkurt

Balcik

Bulgurcuoglu

, et al. Effect of vascular endothelial growth factor on sperm motility and survival. Reprod Biomed Online 2009; 19(6): 784–788. https://doi.org/10.1016/j.rbmo.2009.09.019

Sers

Kirsch

Rothbacher

, et al. Genomic organization of the melanoma-associated glycoprotein MUC18: implications for the evolution of the immunoglobulin domains. Proc Natl Acad Sci U S A 1993; 90(18): 8514–8518. https://doi.org/10.1073/pnas.90.18.8514

Keller

Kalt

Raab

, et al. Selection of scFv antibody fragments binding to human blood versus lymphatic endothelial surface antigens by direct cell phage display. PLoS One 2015; 10(5): e0127169. https://doi.org/10.1371/journal.pone.0127169

10.

Bardin

Blot-Chabaud

Despoix

, et al. CD146 and its soluble form regulate monocyte transendothelial migration. Arterioscler Thromb Vasc Biol 2009; 29(5): 746–753. https://doi.org/10.1161/ATVBAHA.108.183251

11.

Ouhtit

Gaur

Abd Elmageed

, et al. Towards understanding the mode of action of the multifaceted cell adhesion receptor CD146. Biochim Biophys Acta 2009; 1795(2): 130–136. https://doi.org/10.1016/j.bbcan.2009.01.002

12.

Jiang

Zhuang

Duan

, et al. CD146 is a coreceptor for VEGFR-2 in tumor angiogenesis. Blood 2012; 120(11): 2330–2339. https://doi.org/10.1182/blood-2012-01-406108

13.

Matsuo

Imai

Horio

, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 2009; 53(6): 982–992. https://doi.org/10.1053/j.ajkd.2008.12.034

14.

Masuda

Tomita

Ishihama

. Phase transfer surfactant-aided trypsin digestion for membrane proteome analysis. J Proteome Res 2008; 7(2): 731–740. https://doi.org/10.1021/pr700658q

15.

Szklarczyk

Kirsch

Koutrouli

, et al. The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res 2023; 51(D1): D638–D646. https://doi.org/10.1093/nar/gkac1000

16.

Robin

Turck

Hainard

, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinf 2011; 12: 77. https://doi.org/10.1186/1471-2105-12-77

17.

McClure

Healy

Rogers

, et al. Vascular endothelial growth factor as capillary permeability agent in ovarian hyperstimulation syndrome. Lancet 1994; 344(8917): 235–236. https://doi.org/10.1016/s0140-6736(94)93001-5

18.

Tian

Yang

Zhu

, et al. VEGF/VEGFR2 signaling regulates germ cell proliferation in vitro and promotes mouse testicular regeneration in vivo. Cells Tissues Organs 2016; 201(1): 1–13. https://doi.org/10.1159/000440949

19.

Harhouri

Kebir

Guillet

, et al. Soluble CD146 displays angiogenic properties and promotes neovascularization in experimental hind-limb ischemia. Blood 2010; 115(18): 3843–3851. https://doi.org/10.1182/blood-2009-06-229591

20.

Stalin

Nollet

Garigue

, et al. Targeting soluble CD146 with a neutralizing antibody inhibits vascularization, growth and survival of CD146-positive tumors. Oncogene 2016; 35(42): 5489–5500. https://doi.org/10.1038/onc.2016.83

21.

Leroyer

Blin

Bachelier

, et al. CD146 (cluster of differentiation 146). Arterioscler Thromb Vasc Biol 2019; 39(6): 1026–1033. https://doi.org/10.1161/ATVBAHA.119.312653

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