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      Insight on multiple morphological abnormalities of sperm flagella in male infertility: what is new?

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          Abstract

          The syndrome of multiple morphological abnormalities of the sperm flagella (MMAF) is a specific kind of asthenoteratozoospermia with a mosaic of flagellar morphological abnormalities (absent, short, bent, coiled, and irregular flagella). MMAF was proposed in 2014 and has attracted increasing attention; however, it has not been clearly understood. In this review, we elucidate the definition of MMAF from a systematical view, the difference between MMAF and other conditions with asthenoteratozoospermia or asthenozoospermia (such as primary mitochondrial sheath defects and primary ciliary dyskinesia), the knowledge regarding its etiological mechanism and related genetic findings, and the clinical significance of MMAF for intracytoplasmic sperm injection and genetic counseling. This review provides the basic knowledge for MMAF and puts forward some suggestions for further investigations.

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          Plk4-induced centriole biogenesis in human cells.

          Julia Kleylein-Sohn, Jens Westendorf, Mikael Le Clech … (2007)
          We show that overexpression of Polo-like kinase 4 (Plk4) in human cells induces centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole. This provided an opportunity for dissecting centriole assembly and characterizing assembly intermediates. Critical components were identified and ordered into an assembly pathway through siRNA and localized through immunoelectron microscopy. Plk4, hSas-6, CPAP, Cep135, gamma-tubulin, and CP110 were required at different stages of procentriole formation and in association with different centriolar structures. Remarkably, hSas-6 associated only transiently with nascent procentrioles, whereas Cep135 and CPAP formed a core structure within the proximal lumen of both parental and nascent centrioles. Finally, CP110 was recruited early and then associated with the growing distal tips, indicating that centrioles elongate through insertion of alpha-/beta-tubulin underneath a CP110 cap. Collectively, these data afford a comprehensive view of the assembly pathway underlying centriole biogenesis in human cells.
          Article 0 comments Cited 235 times – based on 0 reviews     Review now
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            Mutations in DNAH1, which encodes an inner arm heavy chain dynein, lead to male infertility from multiple morphological abnormalities of the sperm flagella.

            Mariem Ben Khelifa, Charles Coutton, Raoudha Zouari … (2014)
            Ten to fifteen percent of couples are confronted with infertility and a male factor is involved in approximately half the cases. A genetic etiology is likely in most cases yet only few genes have been formally correlated with male infertility. Homozygosity mapping was carried out on a cohort of 20 North African individuals, including 18 index cases, presenting with primary infertility resulting from impaired sperm motility caused by a mosaic of multiple morphological abnormalities of the flagella (MMAF) including absent, short, coiled, bent, and irregular flagella. Five unrelated subjects out of 18 (28%) carried a homozygous variant in DNAH1, which encodes an inner dynein heavy chain and is expressed in testis. RT-PCR, immunostaining, and electronic microscopy were carried out on samples from one of the subjects with a mutation located on a donor splice site. Neither the transcript nor the protein was observed in this individual, confirming the pathogenicity of this variant. A general axonemal disorganization including mislocalization of the microtubule doublets and loss of the inner dynein arms was observed. Although DNAH1 is also expressed in other ciliated cells, infertility was the only symptom of primary ciliary dyskinesia observed in affected subjects, suggesting that DNAH1 function in cilium is not as critical as in sperm flagellum.
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              Mitochondria functionality and sperm quality.

              Monica Telles, Márcio B. Lourenço, Alexandra Amaral … (2012)
              Although mitochondria are best known for being the eukaryotic cell powerhouses, these organelles participate in various cellular functions besides ATP production, such as calcium homoeostasis, generation of reactive oxygen species (ROS), the intrinsic apoptotic pathway and steroid hormone biosynthesis. The aim of this review was to discuss the putative roles of mitochondria in mammalian sperm function and how they may relate to sperm quality and fertilisation ability, particularly in humans. Although paternal mitochondria are degraded inside the zygote, sperm mitochondrial functionality seems to be critical for fertilisation. Indeed, changes in mitochondrial integrity/functionality, namely defects in mitochondrial ultrastructure or in the mitochondrial genome, transcriptome or proteome, as well as low mitochondrial membrane potential or altered oxygen consumption, have been correlated with loss of sperm function (particularly with decreased motility). Results from genetically engineered mouse models also confirmed this trend. On the other hand, increasing evidence suggests that mitochondria derived ATP is not crucial for sperm motility and that glycolysis may be the main ATP supplier for this particular aspect of sperm function. However, there are contradictory data in the literature regarding sperm bioenergetics. The relevance of sperm mitochondria may thus be associated with their role in other physiological features, particularly with the production of ROS, which in controlled levels are needed for proper sperm function. Sperm mitochondria may also serve as intracellular Ca²⁺ stores, although their role in signalling is still unclear.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Asian J Androl
                Journal ID (iso-abbrev): Asian J. Androl
                Journal ID (publisher-id): AJA
                Title: Asian Journal of Andrology
                Publisher: Wolters Kluwer - Medknow (India )
                ISSN (Print): 1008-682X
                ISSN (Electronic): 1745-7262
                Publication date Collection: May-Jun 2020
                Publication date (Electronic): 14 June 2019
                Volume: 22
                Issue: 3
                Pages: 236-245
                Affiliations
                [1 ]Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410078, China
                [2 ]Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha 410078, China
                [3 ]National Engineering and Research Center of Human Stem Cell, Changsha 410078, China
                Author notes
                Correspondence: Dr. YQ Tan ( tanyueqiu@ 123456csu.edu.cn )
                [*]

                These authors contributed equally to this work.

                Article
                Publisher ID: AJA-22-236
                DOI: 10.4103/aja.aja_53_19
                PMC ID: 7275805
                PubMed ID: 31210147
                SO-VID: 1591ab5a-c238-48be-9e77-0141793e7d70
                Copyright © Copyright: ©The Author(s)(2019)
                License:

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                Date received : 27 November 2018
                Date accepted : 22 March 2019
                Categories
                Subject: Review

                Keywords: asthenoteratozoospermia,disease-causing genes,intracytoplasmic sperm injection,male infertility,multiple morphological abnormalities of the sperm flagella
                Data availability:
                Keywords: asthenoteratozoospermia, disease-causing genes, intracytoplasmic sperm injection, male infertility, multiple morphological abnormalities of the sperm flagella

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