Post-translational modifications of seminal proteins and their importance in male fertility potential

Maciel, Valter Luiz; Tamashiro, Letícia Kaory; Bertolla, Ricardo Pimenta

doi:10.1080/14789450.2019.1693895

Cited by 26 publications

(18 citation statements)

References 61 publications

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“…N-glycosylation, one of the most prevalent post-translational protein modifications, plays a significant role in interactions between cells and extracellular matrix as well as in protein folding. The glycosylation pattern was shown to be altered in various diseases and conditions, such as male infertility [ 13 ], where the seminal plasma has been extensively explored, as it offers a rich source of N-glyco-biomarkers [ 50 ]. Although seminal plasma surrounds sperm during a short period, protein glycosylation is stable under physiological conditions and can have a significant impact on protein function, as many adhesive properties result from the protein–carbohydrate interactions.…”

Section: Discussionmentioning

confidence: 99%

Seminal Plasma Protein N-Glycan Peaks Are Potential Predictors of Semen Pathology and Sperm Chromatin Maturity in Men

Marić

Bojanac

Matijević

et al. 2021

Life

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Background: Male infertility is increasingly becoming a health and demographic problem. While it may originate from congenital or acquired diseases, it can also result from environmental exposure. Hence, the complexity of involved molecular mechanisms often requires a multiparametric approach. This study aimed to associate semen parameters with sperm DNA fragmentation, chromatin maturity and seminal plasma protein N-glycosylation. Methods: The study was conducted with 166 participants, 20–55 y old, 82 normozoospermic and 84 with pathological diagnosis. Sperm was analyzed by Halosperm assay and aniline blue staining, while seminal plasma total protein N-glycans were analyzed by ultra-high-performance liquid chromatography. Results: Sperm DNA fragmentation was significantly increased in the pathological group and was inversely correlated with sperm motility and viability. Seminal plasma total protein N-glycans were chromatographically separated in 37 individual peaks. The pattern of seminal plasma N-glycan peaks (SPGP) showed that SPGP14 significantly differs between men with normal and pathological semen parameters (p < 0.001). The multivariate analysis showed that when sperm chromatin maturity increases by 10%, SPGP17 decreases by 14% while SPGP25 increases by 25%. Conclusion: DNA integrity and seminal plasma N-glycans are associated with pathological sperm parameters. Specific N-glycans are also associated with sperm chromatin maturity and have a potential in future fertility research and clinical diagnostics.

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Section: Discussionmentioning

confidence: 99%

Seminal Plasma Protein N-Glycan Peaks Are Potential Predictors of Semen Pathology and Sperm Chromatin Maturity in Men

Marić

Bojanac

Matijević

et al. 2021

Life

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“…Also, it is noteworthy that post-translational modifications occur before proteins are poured into seminal fluid, since we have found similar proteins at different spots. These post-translational modifications, including ubiquitination, phosphorylation, acetylation, sumoylation, and others, may have an important role in sperm due to its transcriptional and traductional inactivity, thus helping in the regulation protein stability and activity both in physiological and pathological states [ 63 ]. Interactions among differential proteins identified in the present study provide a substantial confirmation that ubiquitin C might indeed be involved in sperm fertility regulation ( Figure 3 a,b).…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis in Seminal Plasma of Fertile Donors and Infertile Patients with Sperm DNA Fragmentation

Fernández-Encinas

García-Peiró²,

Rey

et al. 2020

IJMS

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Seminal plasma proteomics studies could represent a new approach for the determination of molecular elements driving male infertility, resulting in a better male infertility characterization. The aim of this study is to investigate proteomic differences in seminal plasma samples from fertile and infertile individuals. For that, semen samples were selected according to semen analysis, clinical pathology, and values of sperm DNA fragmentation (alkaline and neutral Comet assay and Sperm Chromatin Dispersion test). A total of 24 seminal plasma samples classified in four groups were processed: fertile donors (FD), recurrent miscarriage patients (RM), asthenoteratozoospermic patients (ATZ), and asthenoteratozoospermic patients with varicocele (ATZ-VAR). Results obtained by 2D-differential gel electrophoresis (2D-DIGE) revealed 26 spots significantly increased in fertile donors when compared to patient groups. Also, eight spots in the ATZ group and two in the ATZ-VAR group were decreased compared to the other groups. Twenty-eight proteins were identified by mass spectrometry (MS), most of them involved in metabolic and cellular processes and with a catalytic or binding function. Protein–protein interactions through Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) tool suggest that a large part of them were associated with each other. Furthermore, most of them were associated with ubiquitin C, indicating that it could play an important regulation role, resulting in a potential male infertility biomarker.

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“…Considering the mature sperm cell is transcriptionally and translationally quiescent, it must rely on the cumulative efforts of PN components to maintain the fidelity of intrinsic proteins during post-testicular maturation (Maciel et al, 2019). Fittingly, PTMs are crucial for the acquisition of sperm functional competence, playing key roles in capacitationassociated signaling events that underpin hyperactivated motility and oocyte interactions (Aitken and Nixon, 2013;Nixon and Bromfield, 2018).…”

Section: Post-translational Modificationsmentioning

confidence: 99%

“…Highlighting this, excessive levels of reactive nitrogen species (RNS)-induced modifications have been documented in the defective spermatozoa of asthenozoospermic patients (Lefievre et al, 2007;Martinez-Heredia et al, 2008). Additionally, dysregulated glycosylation, acetylation, ubiquitination, and SUMOylation are linked to abnormal sperm morphology and impaired fertilization and embryo development (Samanta et al, 2016;Maciel et al, 2019). These protein modifications represent important examples of the parallels that exist between germ and somatic cell proteostasis.…”

Section: Post-translational Modificationsmentioning

confidence: 99%

Proteostasis in the Male and Female Germline: A New Outlook on the Maintenance of Reproductive Health

Cafe

Nixon

Ecroyd

et al. 2021

Front. Cell Dev. Biol.

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For fully differentiated, long lived cells the maintenance of protein homeostasis (proteostasis) becomes a crucial determinant of cellular function and viability. Neurons are the most well-known example of this phenomenon where the majority of these cells must survive the entire course of life. However, male and female germ cells are also uniquely dependent on the maintenance of proteostasis to achieve successful fertilization. Oocytes, also long-lived cells, are subjected to prolonged periods of arrest and are largely reliant on the translation of stored mRNAs, accumulated during the growth period, to support meiotic maturation and subsequent embryogenesis. Conversely, sperm cells, while relatively ephemeral, are completely reliant on proteostasis due to the absence of both transcription and translation. Despite these remarkable, cell-specific features there has been little focus on understanding protein homeostasis in reproductive cells and how/whether proteostasis is “reset” during embryogenesis. Here, we seek to capture the momentum of this growing field by highlighting novel findings regarding germline proteostasis and how this knowledge can be used to promote reproductive health. In this review we capture proteostasis in the context of both somatic cell and germline aging and discuss the influence of oxidative stress on protein function. In particular, we highlight the contributions of proteostasis changes to oocyte aging and encourage a focus in this area that may complement the extensive analyses of DNA damage and aneuploidy that have long occupied the oocyte aging field. Moreover, we discuss the influence of common non-enzymatic protein modifications on the stability of proteins in the male germline, how these changes affect sperm function, and how they may be prevented to preserve fertility. Through this review we aim to bring to light a new trajectory for our field and highlight the potential to harness the germ cell’s natural proteostasis mechanisms to improve reproductive health. This manuscript will be of interest to those in the fields of proteostasis, aging, male and female gamete reproductive biology, embryogenesis, and life course health.

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Post-translational modifications of seminal proteins and their importance in male fertility potential

Cited by 26 publications

References 61 publications

Seminal Plasma Protein N-Glycan Peaks Are Potential Predictors of Semen Pathology and Sperm Chromatin Maturity in Men

Seminal Plasma Protein N-Glycan Peaks Are Potential Predictors of Semen Pathology and Sperm Chromatin Maturity in Men

Proteomic Analysis in Seminal Plasma of Fertile Donors and Infertile Patients with Sperm DNA Fragmentation

Proteostasis in the Male and Female Germline: A New Outlook on the Maintenance of Reproductive Health

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