Epididymosomes: A potential male fertility influencer

Paul, Nilendu; Nag, Pranab Kumar; Kumaresan, A.

doi:10.1111/and.14155

Cited by 15 publications

(5 citation statements)

References 94 publications

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“…1B ), which can signify that cleavage of ACTL7A or removal of post-translational modifications are required to allow ACTL7A to adequately function in the postacrosomal sheath. It is known that during epididymal transit, sperm acquire motility and fertilization competence, signifying changes in which epididymosome-mediated modifications of sperm proteins, including protein cleavage, have been considered to be a contributing factor ( Zhou et al , 2018 , 2019 ; Paul et al , 2021 ) and could potentially explain the observed size discrepancy and potential proacrosomal function of ACTL7A in sperm. Even though we did not observe changes in motility and sperm capacitation in Actl7a KO sperm, further investigation is needed to see whether this protein plays additional roles in sperm reorganization events such as oocyte fusion.…”

Section: Discussionmentioning

confidence: 99%

Testis-specific actin-like 7A (ACTL7A) is an indispensable protein for subacrosomal-associated F-actin formation, acrosomal anchoring, and male fertility

Ferrer

Upadhyay

Ikawa

et al. 2023

Molecular Human Reproduction

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Formation of the acrosome during spermiogenesis is an essential process for creating fertilization competent sperm. Of the numerous aspects required for acrosome biogenesis, adherence of the acrosomal outer membrane to the nuclear surface is mediated by the subacrosomal perinuclear theca. However, the cellular dynamics and congruent functions pertaining to these acrosomal anchoring factors are not well understood despite many of them being implicated as potential causes for human male infertility. Actin-like protein 7A (ACTL7A) is one such factor for which deleterious polymorphisms have recently been shown to cause human male infertility. It is thought that acrosomal attachment is coordinated by cytoskeletal associations between the acrosome and nucleus via the acroplaxome. To further illuminate the mechanistic underpinnings of ACTL7A for essential acrosome associations, in this study we investigated its dynamic localization in the developing germline, molecular associations with other cytoskeletal components, and the cellular consequences of ablation. Our intracellular localization data shows ACTL7A to be dynamically present within the nucleus and subacrosomal space and later associated with postacrosomal regions of developing spermatids. Through the generation of an Actl7a knock-out mouse model, we consistently observed disruption of acrosomal biogenesis with abnormal migration of the acrosomal granule, and peeling acrosomes during spermatid elongation. Significantly, we found a complete loss of subacrosomal filamentous actin (F-actin) structures in knock-out spermatids suggesting a regulatory role for subacrosomal F-actin. Considering our reported data together with existing literature, we propose a mechanistic model explaining the essential role for ACTL7A for acroplaxome associated F-actin, acrosomal attachment integrity and male fertility.

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Section: Discussionmentioning

confidence: 99%

Testis-specific actin-like 7A (ACTL7A) is an indispensable protein for subacrosomal-associated F-actin formation, acrosomal anchoring, and male fertility

Ferrer

Upadhyay

Ikawa

et al. 2023

Molecular Human Reproduction

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“…The exosomes are mainly proteasomes and epididymosomes [18], the latter being secretion vesicles of the epididymal epithelium that are essential for the acquisition of the fertilizing capacity of the sperm cells. They are rich in sphingomyelins and lipids, but contain also RNAs, proteins, and several metabolites such as amino acids [19,20].…”

Section: Discussionmentioning

confidence: 99%

A Metabolomic Profile of Seminal Fluid in Extremely Severe Oligozoopermia Suggesting an Epididymal Involvement

et al. 2022

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Male infertility has increased in the last decade. Pathophysiologic mechanisms behind extreme oligospermia (EO) are not yet fully understood. In new “omics” approaches, metabolomic can offer new information and help elucidate these mechanisms. We performed a metabolomics study of the seminal fluid (SF) in order to understand the mechanisms implicated in EO. We realized a targeted quantitative analysis using high performance liquid chromatography and mass spectrometry to compare the SF metabolomic profile of 19 men with EO with that of 22 men with a history of vasectomy (V) and 20 men with normal semen parameters (C). A total of 114 metabolites were identified. We obtained a multivariate OPLS-DA model discriminating the three groups. Signatures show significantly higher levels of amino acids and polyamines in C group. The sum of polyunsaturated fatty acids and free carnitine progressively decrease between the three groups (C > EO > V) and sphingomyelins are significantly lower in V group. Our signature characterizing EO includes metabolites already linked to infertility in previous studies. The similarities between the signatures of the EO and V groups are clear evidence of epididymal dysfunction in the case of testicular damage. This study shows the complexity of the metabolomic dysfunction occurring in the SF of EO men and underlines the importance of metabolomics in understanding male infertility.

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“…The compounds accumulated in epididymosomes are delivered to maturing spermatozoa through several possible mechanisms, such as lipid raft‐mediated protein delivery to sperm surface, formation of transient fusion pores on sperm surface, and glycosyl phosphatidylinositol‐(GPI)‐linked protein delivery to sperm surface via lipid carriers. [ 130 ] Epididymosomes have been discovered to perform different functions in sperm physiology. For instance, one of the known constituents of the vesicles is MIF as a classical T‐cell cytokine, which could eliminate Zn +2 by influencing free sulfhydryl groups in sperm flagellum during the maturational development, thereby modulating sperm motility.…”

Section: Exos Source In the Reproductive Systemmentioning

confidence: 99%

Exosomes as Theranostic Agents in Reproduction System

Izadpanah,

Yalameha,

Sani

et al. 2023

Advanced Biology

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Exosomes (Exos), belonging to extracellular vesicles, are cell‐derived nano‐sized vesicles with the potential to carry different kinds of biological molecules. Many studies have proved the impacts of exosomal cargo on several biological processes in female and male reproductive systems. It is also hypothesized that changes in exosomal cargo are integral to the promotion of certain pathological conditions, thus Exos can be used as valid biomarkers for the diagnosis of infertility and other abnormal conditions. Here, efforts are made to collect some recent data related to the physiological significance of Exos in the reproductive system, and their potential therapeutic effects. It is anticipated that the current review article will lay the groundwork for elucidating the source and mechanisms by which Exos control the reproductive system additionally supplying fresh methods and concepts for the detection and treatment of disorders associated with fertility for future studies.

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Epididymosomes: A potential male fertility influencer

Cited by 15 publications

References 94 publications

Testis-specific actin-like 7A (ACTL7A) is an indispensable protein for subacrosomal-associated F-actin formation, acrosomal anchoring, and male fertility

Testis-specific actin-like 7A (ACTL7A) is an indispensable protein for subacrosomal-associated F-actin formation, acrosomal anchoring, and male fertility

A Metabolomic Profile of Seminal Fluid in Extremely Severe Oligozoopermia Suggesting an Epididymal Involvement

Exosomes as Theranostic Agents in Reproduction System

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