Evaluation of PGK2 and ACR proteins in seminal plasma: suggestion of potential new biomarkers for prediction of sperm retrieval in non-obstructive azoospermia patients

Gashti, Nasrin Ghanami; Gilani, Mohammad Ali Sadighi; Kabodmehri, Roya; Nikmahzar, Aghbibi; Salem, Maryam; Abbasi, Mehdi

doi:10.1080/14647273.2022.2104136

Cited by 1 publication

(2 citation statements)

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“…Seminal plasma is a biological fluid that is routinely collected during work up of the infertile male, and thus analysis of the seminal plasma proteome holds promise for the discovery of markers of male infertility that could predict the outcome of sperm retrieval in azoospermic men ( 20 , 28 , 30 ). Despite some promising results from validation studies ( 31 , 32 ) there are no defined clinical biomarkers in seminal plasma that can be used for the differential diagnosis of azoospermia prior to surgical intervention.…”

Section: Discussionmentioning

confidence: 99%

“…There is emerging evidence that the levels of germ cell-specific proteins in seminal plasma can correlate with male reproductive potential in NOA patients ( 20 , 31 ). However, specific candidate proteins differ greatly from one study to another, which represents a major hurdle in linking particular forms of azoospermia to specific seminal plasma biomarkers.…”

Section: Discussionmentioning

confidence: 99%

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Proteomic biomarkers in seminal plasma as predictors of reproductive potential in azoospermic men

Fietz,

Sgaier,

O’Donnell

et al. 2024

Front. Endocrinol.

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IntroductionAzoospermia, characterized by an absence of sperm in the ejaculate, represents the most severe form of male infertility. While surgical sperm retrieval in obstructive azoospermia (OA) is successful in the majority of cases, patients with non-obstructive azoospermia (NOA) show retrieval rates of only about 50% and thus frequently have unnecessary surgery. Surgical intervention could be avoided if patients without preserved spermatogenesis are identified preoperatively. This prospective study aimed to discover biomarkers in seminal plasma that could be employed for a non-invasive differential diagnosis of OA/NOA in order to rationalize surgery recommendations and improve success rates.MethodsAll patients signed written informed consent, underwent comprehensive andrological evaluation, received human genetics to exclude relevant pathologies, and patients with azoospermia underwent surgical sperm retrieval. Using label-free LC-MS/MS, we compared the proteomes of seminal plasma samples from fertile men (healthy controls (HC), n=8) and infertile men diagnosed with 1) OA (n=7), 2) NOA with successful sperm retrieval (mixed testicular atrophy (MTA), n=8), and 3) NOA without sperm retrieval (Sertoli cell-only phenotype (SCO), n=7). Relative abundance changes of two candidate markers of sperm retrieval, HSPA2 and LDHC, were confirmed by Western Blot.ResultsWe found the protein expression levels of 42 proteins to be significantly down-regulated (p ≤ 0.05) in seminal plasma from SCO NOA patients relative to HC whereas only one protein was down-regulated in seminal plasma from MTA patients. Analysis of tissue and cell expression suggested that the testis-specific proteins LDHC, PGK2, DPEP3, and germ-cell enriched heat-shock proteins HSPA2 and HSPA4L are promising biomarkers of spermatogenic function. Western blotting revealed a significantly lower abundance of LDHC and HSPA2 in the seminal plasma of men with NOA (SCO and MTA) compared to controls.DiscussionThe results indicate that certain testis-specific proteins when measured in seminal plasma, could serve as indicators of the presence of sperm in the testis and predict the success of sperm retrieval. Used in conjunction with conventional clinical assessments, these proteomic biomarkers may assist in the non-invasive diagnosis of idiopathic male infertility.

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