A5080885531- Sperm and Testicular Function
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Reproductive Biology and Fertility
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Animal Genetics and Reproduction
- Advanced Proteomics Techniques and Applications
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Microtubule and mitosis dynamics
- Health, Environment, Cognitive Aging
- Reproductive System and Pregnancy
- Ubiquitin and proteasome pathways
- Lipid metabolism and biosynthesis
- Genetic and Kidney Cyst Diseases
- Caveolin-1 and cellular processes
- Histone Deacetylase Inhibitors Research
- Ovarian function and disorders
- Apelin-related biomedical research
- Erythrocyte Function and Pathophysiology
- Demographic Trends and Gender Preferences
- Cellular transport and secretion
- Renal and related cancers
- RNA Interference and Gene Delivery
Université Paris Cité
2013-2025
Institut Cochin
2016-2025
Inserm
2013-2025
Centre National de la Recherche Scientifique
2014-2023
Délégation Paris 5
2014-2021
Sorbonne Paris Cité
2017-2021
Descartes (Belgium)
2019
Centre de Gestion Scientifique
2014-2019
Sorbonne Université
2017
Glycylation regulates axonemal dyneins Physiological functions of the microtubule cytoskeleton are expected to be regulated by a variety posttranslational tubulin modifications. For instance, glycylation is almost exclusively found in cilia and flagella, but its role function these organelles remains unclear. Gadadhar et al. now demonstrate mice that glycylation, although nonessential for formation coordinates beat waveform sperm flagella. This activity prerequisite progressive swimming thus...
Three genes are known to be essential for gamete adhesion/fusion (Cd9, Izumo1 and Juno). Here, we confirmed that Spaca6 null males infertile showed their sperm accumulate in the perivitelline space but unable fuse with oocyte. Like IZUMO1, SPACA6 which is expressed by human sperm, remained on equatorial segment after acrosomal reaction involved fertilization since an anti-SPACA6 antibody inhibited it. Despite similarity of phenotypes caused knockouts, these not redundant relocation IZUMO1...
The mouse sex chromosomes exhibit an extraordinary level of copy number amplification postmeiotically expressed genes [1Mueller J.L. Mahadevaiah S.K. Park P.J. Warburton P.E. Page D.C. Turner J.M.A. X chromosome is enriched for multicopy testis showing postmeiotic expression.Nat. Genet. 2008; 40: 794-799Crossref PubMed Scopus (223) Google Scholar, 2Soh Y.Q.S. Alföldi J. Pyntikova T. Brown L.G. Graves Minx Fulton R.S. Kremitzki C. Koutseva N. Mueller et al.Sequencing the Y reveals convergent...
Abstract The H3K79 methyltransferase DOT1L is essential for multiple aspects of mammalian development where it has been shown to regulate gene expression. Here, by producing and integrating epigenomic spike-in RNA-seq data, we decipher the molecular role during mouse spermatogenesis show that opposite effects on expression depending chromatin environment. On one hand, represses autosomal genes are devoid H3K79me2 at their bodies located in H3K27me3-rich/H3K27ac-poor environments. other...
Drastic membrane reorganization occurs when mammalian sperm binds to and fuses with the oocyte membrane. Two protein families are essential for fertilization, tetraspanins glycosylphosphatidylinositol-anchored proteins. The firsts associated tetraspanin-enriched microdomains seconds lipid rafts. Here we report raft involvement in mouse fertilization assessed by cholesterol modulation using methyl-β-cyclodextrin. Cholesterol removal induced: (1) a decrease of rate index; (2) delay extrusion...
Sperm differentiation requires unique transcriptional regulation and chromatin remodeling after meiosis to ensure proper compaction protection of the paternal genome. Abnormal sperm can induce DNA damage, embryo lethality male infertility, yet, little is known about factors which regulate this process. Deficiency in Sly, a mouse Y chromosome-encoded gene expressed only postmeiotic germ cells, has been shown result deregulation hundreds sex genes associated with multiple defects subsequent...
Abstract Transmission distorters (TDs) are genetic elements that favor their own transmission to the detriments of others. Slx/Slxl1 (Sycp3-like-X-linked and Slx-like1) Sly (Sycp3-like-Y-linked) TDs, which have been coamplified on X Y chromosomes Mus species. They involved in an intragenomic conflict each favors its transmission, resulting sex ratio distortion progeny when versus copy number is unbalanced. specifically expressed male postmeiotic gametes (spermatids) opposite effects gene...
Epigenetic regulation of gene expression is tightly controlled by the dynamic modification histones chemical groups, diversity which has largely expanded over past decade with discovery lysine acylations, catalyzed from acyl-coenzymes A. We investigated dynamics acetylation and crotonylation on H3 H4 during mouse spermatogenesis. Lysine appeared to be significant abundance compared acetylation, particularly Lys27 histone (H3K27cr) that accumulates in sperm a cleaved form H3. identified...
Spermatozoa have a unique genome organization. Their chromatin is almost completely devoid of histones and formed instead protamines, which confer high level compaction preserve paternal integrity until fertilization. Histone-to-protamine transition takes place in spermatids indispensable for the production functional sperm. Here, we show that H3K79-methyltransferase DOT1L controls spermatid remodeling subsequent reorganization spermatozoon genome. Using mouse model Dot1l knocked-out (KO)...
In mammals, X- and Y-encoded genes are transcriptionally shut down during male meiosis, but expression of many them is (re)activated in spermatids after meiosis. Post-meiotic XY gene regulated by active epigenetic marks, which de novo incorporated the sex chromatin spermatids, repressive marks inherited meiosis; alterations this process lead to infertility. mouse, post-meiotic known depend on genetic information carried male-specific region Y chromosome long arm (MSYq). The MSYq Sly has been...
Histones organize DNA into chromatin through a variety of processes. Among them, vast diversity histone variants can be incorporated and finely modulate its organization functionality. Classically, the study has largely relied on antibody-based assays. However, antibodies have limited efficiency to discriminate between highly similar variants. In this study, we established mass spectrometry-based analysis address challenge. We developed targeted proteomics method, using selected reaction...
Thanks to the analysis of an Interspecific Recombinant Congenic Strain (IRCS), we previously defined Mafq1 quantitative trait locus as interval on mouse Chromosome 1 associated with male hypofertility and ultrastructural abnormalities. We identified Spermatogenesis protein 3 gene (Spata3 or Tsarg1) a pertinent candidate within performed CRISPR-Cas9 mediated complete deletion investigate its function. Male mice deleted for Spata3 were normally fertile in vivo but exhibited drastic reduction...
Abstract Chromatin of male and female gametes undergoes a number reprogramming events during the transition from germ cell to embryonic developmental programs. Although rearrangement DNA methylation patterns occurring in zygote has been extensively characterized, little is known about dynamics modifications spermatid maturation. Here, we demonstrate that 5-carboxylcytosine (5caC) correlate with active transcription LINE-1 retroelements murine spermiogenesis. We show open reading frames...
In mammalian fertilization, the link between oocyte plasma membrane and underneath cytoskeleton has often been associated to key elements of successful gamete fusion, like microvilli shaping or CD9 function, but its effective role poorly studied. EWI-2 EWI-F as cis partners CD9, ERM proteins (Ezrin, Radixin Moesin) that both attach actin EWI are part molecules make cytoskeleton. This study aims assay through siRNA inhibition, involvement these in mouse their morphology egg also possible...
We have previously shown, using antibodies, that the sperm alpha6beta1 integrin is involved in mouse gamete fusion vitro. Here we report conditional knockdown of Itgb1 gene. It induced a drastic failure fusogenic ability with accumulation perivitelline space vitro inseminated oocytes deleted or not for These data demonstrate sperm, but oocyte, beta1 subunit adhesion/fusion. Curiously, males were fertile vivo probably because incomplete Cre-mediated deletion floxed Indeed, this was shown by...
Male fertility disorders often have their origin in disturbed spermatogenesis, which can be induced by genetic factors. In this study, we used interspecific recombinant congenic mouse strains (IRCS) to identify genes responsible for male infertility. Using ultrasonography, vivo and vitro fertilization (IVF) electron microscopy, the phenotyping of several IRCS carrying chromosome 1 segments Mus spretus revealed a decrease ability sperm fertilize. This teratozoospermia included abnormal...
Recently, Juno, the oocyte receptor for Izumo1, a male immunoglobulin, was discovered. Juno is an essential glycosylphosphatidylinositol (GIP)-anchored protein. This result did not exclude participation of other GIP-anchored proteins in this process. After bibliographic and database searches we selected five (Cpm, Ephrin-A4, Gas1, Gfra1 Rgmb) as potential candidates participating fertilisation. Western blot immunofluorescence analyses showed that only three were present on mouse ovulated...
By analyzing a mouse Interspecific Recombinant Congenic Strain (IRCS), we previously identified quantitative trait locus (QTL), called Mafq1 on chromosome 1, that is associated with male hypofertility and ultrastructural sperm abnormalities. Within this locus, new candidate gene could be implicated in reproductive phenotype: Tex44 (Testis-expressed protein 44). We thus performed CRISPR/Cas9-mediated complete deletion of mice order to study its function. Tex44-KO males were severely...
Abstract The H3K79 methyltransferase DOT1L is essential for multiple aspects of mammalian development where it has been shown to regulate gene expression. Here, by producing and integrating epigenomic spike-in RNA-seq data, we deciphered the molecular role during mouse spermatogenesis show that opposite effects on expression depending chromatin environment. On one hand, represses autosomal genes are devoid H3K79me2 at their bodies located in H3K27me3-rich/H3K27ac-poor environments. other...
Spermiogenesis is the step during which post-meiotic cells, called spermatids, undergo numerous morphological changes and differentiate into spermatozoa. Thousands of genes have been described to be expressed at this stage could contribute spermatid differentiation. Genetically-engineered mouse models using Cre/LoxP or CrispR/Cas9 are favored approaches characterize gene function better understand genetic basis male infertility. In present study, we produced a new spermatid-specific Cre...
Summary The search for morphological or physiological differences between X- and Y-bearing mammalian sperm has provoked controversy decades. Many potential have been proposed, but none validated, while accumulating understanding of syncytial development cast doubt on whether such are possible even in principle. We present the first ever experimental model to trace a direct link from measurable difference resulting skewed sex ratio. show that mice with deletions chromosome Yq, birth ratio...
Fertilization is a complex process that requires successive stages and culminates in the adhesion/fusion of gamete membranes. If question involvement oocyte integrins has been swept away by deletion experiments, sperm remains to be further characterized. In present study, we addressed feasibility sperm–oocyte early implantation absence β1 integrin. Males females with integrin-depleted oocytes were mated, fertilization outcome was monitored gestational ultrasound analysis. Results suggest...