ORCID Profile
0000-0002-2807-7048
Current Organisation
Justus Liebig Universitat Giessen
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Publisher: The Endocrine Society
Date: 05-09-2019
Abstract: Ciliated bronchial epithelium 1 (CBE1) is a microtubule-associated protein localized to the manchette and developing flagellum during spermiogenesis, and associated with sperm maturation arrest in humans. It was hypothesized that CBE1 functions in microtubule-mediated transport mechanisms and sperm tail formation. To test this hypothesis, we analysed Cbe1 expression and localization during spermiogenesis, and in mouse IMCD3 cells as a model of ciliogenesis. Further, we generated and analysed the fertility of a Cbe1 mutant mouse line. Mice containing a homozygous deletion in the long forms of Cbe1 were born at a lower frequency than predicted by Mendelian inheritance, however, adult male mice were fertile. An in-depth analysis of the Cbe1 gene revealed alternative transcript variants, which were not affected by the exon 2 mutation. To assess whether short variants compensate for the loss of long variants, exons 2 and 4 (which affect all variants) were in idually mutated in IMCD3 cells and the effect on cell proliferation and ciliogenesis analysed. In wild type IMCD3 cells, both variants were upregulated during cilia assembly. CBE1 protein was not a structural component of cilia, rather, CBE1 localised to the mitochondria and the contractile ring of iding IMCD3 cells. While IMCD3 cells carrying the mutation in long variants showed no phenotypic alterations, the mutation in exon 4 resulted in a significantly decreased proliferation rate. This study reveals that long isoforms of CBE1 are not essential for male fertility. Data, however, suggests that CBE1 is associated to intra-manchette transport and mid-piece formation of the sperm tail.
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.JRI.2022.103618
Abstract: The cytokine activin A is expressed throughout testicular development and is a critical regulator of macrophage function, but its effects on the testicular macrophages are not well-defined. Macrophage distribution and gene transcript levels were examined in testes of adult mice with reduced levels of either activin A (Inhba
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.FERTNSTERT.2016.08.043
Abstract: To define the stage-by-stage expression of KATNB1 during human spermatogenesis. Gene expression analysis, histologic and immunohistochemical evaluation. University research laboratories and andrological clinic. Eighty human testicular biopsy s les: 43 showing normal spermatogenesis, 9 with maturation arrest at level of spermatocytes, 8 with maturation arrest at level of spermatogonia, and 20 with a Sertoli cell only syndrome. None. Evaluation of katanin p80 expression in normal as well as impaired spermatogenesis on mRNA (RT-PCR, RT-qPCR, and in situ hybridization) and protein level (immunohistochemistry/immunofluorescence). KATNB1 messenger RNA is exclusively expressed in germ cells, and quantitatively reduced in maturation arrests at the level of spermatogonia. The KATNB1 protein was detected in type B spermatogonia entering meiosis and in the Golgi complex of pachytene spermatocytes. Immediately before the first meiotic ision, it is colocalized with the cleaving centriole. It was also detected in early round spermatids in the dictyosome. The expression and localization of KATNB1 support a role in spindle formation. The localization of KATNB1 in early round spermatids suggests an involvement in the formation of microtubule-based structures during spermiogenesis (manchette and flagellum). These data are consistent with the demonstrated role of KATNB1 in mouse meiosis, nuclear shaping, and flagellum formation of sperm and suggest the strong conservation of function even between distantly related species.
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.FERTNSTERT.2017.05.019
Abstract: To define the precise cellular localization of ciliated bronchial epithelium 1 (CBE1) in the human testis and test its relationship to impaired spermatogenesis. Gene expression analysis, and histologic and immunohistochemical evaluation. University research laboratories and andrologic outpatient clinic. Forty-three human testicular biopsies: 12 biopsies showing normal spermatogenesis (NSP), 8 with maturation arrest at level of spermatocytes (STA), 8 with maturation arrest at level of spermatids (SDA), 4 with scattered elongating spermatids, and 12 with Sertoli cell-only syndrome, with an additional 5 semen s les from healthy donors. None. Evaluation of CBE1 expression in normal as well as impaired spermatogenesis on mRNA (quantitative reverse-transcription polymerase chain reaction and in situ hybridization) and protein level (immunohistochemistry, Western blot analysis). In normal spermatogenesis, CBE1 mRNA was expressed in late pachytene spermatocytes, and the protein was localized within the flagellum of elongating spermatids from stage V up to the spermiation in stage II. Immunoelectron microscopy showed CBE1 clearly associated with microtubules at the manchette, the head-tail coupling apparatus, and the flagellum, but the protein was absent in spermatozoa. Compared with normal spermatogenesis, CBE1 mRNA was statistically significantly reduced in s les with a maturation arrest at the level of round spermatids and primary spermatocytes, and was absent in s les showing Sertoli cell-only syndrome. CBE1 protein was completely missing in SDA s les showing few elongating spermatids. Our data strongly suggest an influence of CBE1 in ciliogenesis in spermatids due to the localization at the microtubules of the elongating spermatids, indicating a role in the intramanchette and/or intraflagellar transport mechanism. The absence of CBE1 in spermatozoa suggests that CBE1 is important for the spermatid development but not for the maintenance of mature spermatozoa as a component of the flagellum.
Publisher: Proceedings of the National Academy of Sciences
Date: 28-12-2020
Abstract: Infection/inflammation is a major contributor to male infertility, and macrophages are likely to be key players in both pathological progression and resolution of the inflammation. We report that macrophage populations in the epididymis and testis are derived from fetal and neonatal monocytes, which are self-maintaining during adulthood. Furthermore, during inflammation, circulating monocytes recruited to the epididymis and testis give rise to inflammatory macrophages that promote tissue damage. These data are significant for our understanding of the origins and maintenance of macrophage subpopulations in both organs our results point to a fundamental mechanism underpinning male infertility by infection and inflammation, and pave the way for the development of innovative therapeutics to treat this important and common condition.
Publisher: Oxford University Press (OUP)
Date: 21-04-2020
Abstract: The precise movement of proteins and vesicles is an essential ability for all eukaryotic cells. Nowhere is this more evident than during the remarkable transformation that occurs in spermiogenesis—the transformation of haploid round spermatids into sperm. These transformations are critically dependent upon both the microtubule and the actin cytoskeleton, and defects in these processes are thought to underpin a significant percentage of human male infertility. This review is aimed at summarising and synthesising the current state of knowledge around protein/vesicle transport during haploid male germ cell development and identifying knowledge gaps and challenges for future research. To achieve this, we summarise the key discoveries related to protein transport using the mouse as a model system. Where relevant, we anchored these insights to knowledge in the field of human spermiogenesis and the causality of human male infertility. Relevant studies published in English were identified using PubMed using a range of search terms related to the core focus of the review—protein/vesicle transport, intra-flagellar transport, intra-manchette transport, Golgi, acrosome, manchette, axoneme, outer dense fibres and fibrous sheath. Searches were not restricted to a particular time frame or species although the emphasis within the review is on mammalian spermiogenesis. Spermiogenesis is the final phase of sperm development. It results in the transformation of a round cell into a highly polarised sperm with the capacity for fertility. It is critically dependent on the cytoskeleton and its ability to transport protein complexes and vesicles over long distances and often between distinct cytoplasmic compartments. The development of the acrosome covering the sperm head, the sperm tail within the ciliary lobe, the manchette and its role in sperm head shaping and protein transport into the tail, and the assembly of mitochondria into the mid-piece of sperm, may all be viewed as a series of overlapping and interconnected train tracks. Defects in this redistribution network lead to male infertility characterised by abnormal sperm morphology (teratozoospermia) and/or abnormal sperm motility (asthenozoospermia) and are likely to be causal of, or contribute to, a significant percentage of human male infertility. A greater understanding of the mechanisms of protein transport in spermiogenesis offers the potential to precisely diagnose cases of male infertility and to forecast implications for children conceived using gametes containing these mutations. The manipulation of these processes will offer opportunities for male-based contraceptive development. Further, as increasingly evidenced in the literature, we believe that the continuous and spatiotemporally restrained nature of spermiogenesis provides an outstanding model system to identify, and de-code, cytoskeletal elements and transport mechanisms of relevance to multiple tissues.
No related grants have been discovered for Christiane Pleuger.