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. 2023 Oct 31;12(10):1497-1510.
doi: 10.21037/tau-23-130. Epub 2023 Oct 24.

Proteomic approach towards identification of seminal fluid biomarkers from individuals with severe oligozoospermia, cryptozoospermia and non-obstructive azoospermia: a pilot study

Karolina Nowicka-Bauer  1 , Marzena Kamieniczna  1 , Marta Olszewska  1 , Maciej Krzysztof Kurpisz  1
Affiliations

Proteomic approach towards identification of seminal fluid biomarkers from individuals with severe oligozoospermia, cryptozoospermia and non-obstructive azoospermia: a pilot study

Karolina Nowicka-Bauer et al. Transl Androl Urol. .

Abstract

Background: Infertility becomes a global problem that affects to the same extent females and males. As reasons of male infertility can differ among individuals, the accurate diagnostics is essential for effective treatment. The most problematic both in diagnostics and in treatment are disturbances of spermatogenesis. Seminal fluid is rich in proteins that potentially can serve as markers for male infertility and among them, markers of spermatogenesis which are highly desired.

Methods: To find biomarkers of spermatogenesis, we applied comparative proteomics using nano ultra performance liquid chromatography and tandem mass spectrometry (nanoUPLC-MS/MS) followed by single-sample Western blotting (WB) using seminal fluid samples from males with different types of infertility including non-obstructive azoospermia (NOA), cryptozoospermia (C) and severe oligozoospermia (SO). Then, the extensive survey on the identified proteins and their function in male reproductive system has been done.

Results: The proteomic approach has enabled to identified five seminal fluid proteins being potential markers of spermatogenesis disorders: ADGRG2, RAB3B, LTF, SLC2A3 and spermine synthase (SMS). Among them ADGRG2 seems to be strongly involved in male infertility. In addition, WB indicated that the distribution of LTF, SLC2A3 and SMS was not coherent among the individuals, especially in a group with NOA. Functional annotation analysis and search in proteomics databases revealed that vast majority of the proteins originated from extracellular environment.

Conclusions: The presented data point out several proteins that potentially can become biomarkers of male infertility. The data suggest, however, different mechanisms behind the male infertility indicating that the etiology is more complex. We assume that recognition of these mechanisms may lead to the creation of specific protein panel helpful in the management of male infertility and therefore, further studies are required.

Keywords: Spermatogenesis; biomarkers; male infertility; pathological spermiogram; proteomics.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-130/coif). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Venn diagram presenting the distribution of identified proteins within the tested groups. Normozoospermia (Control). SO, severe oligozoospermia; C, cryptozoospermia; NOA, non-obstructive azoospermia.
Figure 2
Figure 2
A scheme representing numbers of DEPs in cohorts of infertile males after quantification and statistical analysis using Diffprot (23,24). DEPs, differentially expressed proteins.
Figure 3
Figure 3
Western blot analysis of seminal plasma samples for ADGRG2 and RAB3B proteins. ADGRG2 is the only protein of which expression was significantly decreased in samples from all groups of patients (C, SO and NOA). For RAB3B, the expression level was significantly decreased in samples of NOA patients compared to controls. All signals were normalized against total protein level. A star refers to the internal reference sample. The error bars indicate standard deviation. * indicates P<0.01. C, cryptozoospermia; SO, severe oligozoospermia; NOA, non-obstructive azoospermia.
Figure 4
Figure 4
Western blot analysis of seminal plasma samples for LTF, SLC2A3 and SMS proteins. Although the differences in expression levels were out statistical importance, for all the three proteins there was visible strong heterogeneity among signals obtained from individual samples of NOA patients. All signals were normalized against total protein level. The error bars indicate standard deviation. *, refers to the internal reference sample. NOA, non-obstructive azoospermia.
Figure 5
Figure 5
The enriched String analysis of PPI of DEPs from seminal plasma samples obtained from (A) severe oligozoospermia, (B), cryptozoospermia and (C) non obstructive azoospermia patients. PPI, protein-protein interaction; DEPs, differentially expressed proteins.
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