Urologist V.I. Kulakov National Medical Research Center
Introduction: Despite large amounts of evidence linking varicocele to male infertility, the role of varicocele repair in infertile men is controversial. Even after technically perfect operation not all couples achieve pregnancy or at least have a significant improvement in semen parameters. Probably, there are cases of infertility which share a causal relationship with varicocele, and there are cases when idiopathic infertility co-exists with harmless varicocele. Unfortunately, there is no way to predict response to varicocele treatment among infertile males. Since sperm are transcriptionally inert, the proteome of seminal plasma is relatively stable and may reflect the true extent of deleterious effects of varicocele, such as oxidative stress and hyperthermia. Our goal was to assess whether proteomic signature of seminal plasma may help to distinguish responders and non-responders to varicocele repair.
Methods: We used mass-spectrometry to perform a proteomic analysis of seminal plasma specimens obtained from 10 infertile patients (age: 25-44 years) with bilateral varicocele. All patients underwent routine semen analysis and had at least two altered core parameters out of three (total sperm count, progressive motility, percentage of sperm with normal morphology). Microsurgical bilateral subinguinal varicocelectomy was performed in all patients. Routine semen analysis and proteomic analysis were repeated at follow-up, which was scheduled at 6 months after the surgery. Responders were defined as patients whose spouse became pregnant during follow-up period or whose total motile sperm count increased by at least 50%. Proteomic profiles of responders and non-responders were compared.
Results: Five patients were responders to varicocele repair (partners of two of them became pregnant). Proteomic analysis identified 18 proteins with differential expression in responders and non-responders: melanophilin, kallikrein-2, alpha-actinin-4, Kunitz-type protease inhibitor 3, alpha-1-acid glycoprotein 1, CD177 antigen, alpha-1-acid glycoprotein 2, protein-glutamine gamma-glutamyltransferase 4, phosphatidylethanol amine-binding protein 4, acyl-CoA-binding protein, hemoglobin subunit alpha, antileukoproteinase, collagen alpha-1(XVIII) chain, vitronectin, serine protease HTRA1, V-type proton ATPase catalytic subunit A, endoplasmic reticulum resident protein 44, NADP-dependent malic enzyme.
Conclusions: If validated, semen proteomics may become a useful tool to predict response to varicocele repair and avoid unnecessary surgery.
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