A5069757119- Sperm and Testicular Function
- Reproductive Biology and Fertility
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Genetic and Kidney Cyst Diseases
- Renal and related cancers
- Microtubule and mitosis dynamics
- Trypanosoma species research and implications
- Prenatal Screening and Diagnostics
- Reproductive Health and Technologies
- Sexual Differentiation and Disorders
- Genetic Syndromes and Imprinting
- CRISPR and Genetic Engineering
- Animal Genetics and Reproduction
- Assisted Reproductive Technology and Twin Pregnancy
- Urologic and reproductive health conditions
- Ovarian function and disorders
- Nuclear Structure and Function
- Chromosomal and Genetic Variations
- Kruppel-like factors research
- Genomic variations and chromosomal abnormalities
- Urological Disorders and Treatments
- Gestational Trophoblastic Disease Studies
- Dye analysis and toxicity
- Epilepsy research and treatment
- Nuts composition and effects
Université Grenoble Alpes
2016-2025
Inserm
2016-2025
Centre National de la Recherche Scientifique
2016-2025
Centre Hospitalier Universitaire de Grenoble
2015-2025
Institut polytechnique de Grenoble
2018-2025
Institut de Biosciences et Biotechnologies
2015-2025
Institut pour l'avancée des biosciences
2015-2025
University of Bayreuth
2023-2024
Yale University
2024
University of California, Los Angeles
2024
Spermatogenesis defects concern millions of men worldwide, yet the vast majority remains undiagnosed. Here we report with primary infertility due to multiple morphological abnormalities sperm flagella severe disorganization axoneme, a microtubule-based structure highly conserved throughout evolution. Whole-exome sequencing was performed on 78 patients allowing identification 22 bi-allelic mutations in DNAH1 (n = 6), CFAP43 10), and CFAP44 6). CRISPR/Cas9 created homozygous CFAP43/44 male...
In mammals, sperm-oocyte fusion initiates Ca(2+) oscillations leading to a series of events called oocyte activation, which is the first stage embryo development. signaling elicited by delivery an oocyte-activating factor sperm. A sperm-specific phospholipase C (PLCZ1) has emerged as likely candidate induce activation. Recently, PAWP, sperm-born tryptophan domain-binding protein coded WBP2NL, was proposed serve same purpose. Here, we studied two infertile brothers exhibiting normal sperm...
Can whole-exome sequencing (WES) of patients with multiple morphological abnormalities the sperm flagella (MMAF) identify causal mutations in new genes or previously identified dynein axonemal heavy chain 1 (DNAH1) gene? WES for six families men affected by MMAF syndrome allowed identification DNAH1 four distributed two out but no candidate were identified. Mutations DNAH1, an inner arm gene, have been shown to be responsible male infertility due a characteristic form asthenozoospermia...
Can whole-exome sequencing (WES) of infertile patients identify new genes responsible for multiple morphological abnormalities the sperm flagella (MMAF)? WES analysis 78 men with a MMAF phenotype permitted identification four homozygous mutations in fibrous sheath (FS) interacting protein 2 (FSIP2) gene unrelated individuals. The use high-throughput techniques revealed that dynein axonemal heavy chain 1 (DNAH1) gene, and cilia associated 43 (CFAP43) 44 (CFAP44) account approximately...
Azoospermia, characterized by the absence of spermatozoa in ejaculate, is a common cause male infertility with poorly etiology. Exome sequencing analysis two azoospermic brothers allowed identification homozygous splice mutation SPINK2, encoding serine protease inhibitor believed to target acrosin, main sperm acrosomal protease. In accord these findings, we observed that Spink2 KO mice had azoospermia. Moreover, despite normal fertility, heterozygous high rate morphologically abnormal and...
Asthenozoospermia, characterized by reduced sperm motility, is a common cause of male infertility. Multiple morphological abnormalities the flagella (MMAF) represent severe and genetically heterogeneous form asthenozoospermia. Over 50 genes have been associated, but approximately half MMAF cases remain unexplained. DRC1, gene involved in nexin-dynein regulatory complex (N-DRC), has linked to primary ciliary dyskinesia (PCD), often with significant variability clinical presentation. His study...
Research Article16 April 2018Open Access Transparent process PATL2 is a key actor of oocyte maturation whose invalidation causes infertility in women and mice Marie Christou-Kent Genetics, Epigenetics Therapies Infertility, Institute for Advanced Biosciences, Inserm U1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France Search more papers by this author Zine-Eddine Kherraf Amir Amiri-Yekta UM GI-DPI, CHU de Department Reproductive Biomedicine Center, Royan Biomedicine, ACECR,...
Background Male infertility due to multiple morphological abnormalities of the sperm flagella (MMAF) is a genetically heterogeneous disorder. Previous studies revealed several MMAF-associated genes, which account for approximately 60% human MMAF cases. The pathogenic mechanisms remain be illuminated. Methods and results We conducted genetic analyses using whole-exome sequencing in 50 Han Chinese probands with MMAF. Two homozygous stop-gain variants (c.910C>T (p.Arg304*) c.3400delA...
Male infertility is a prevalent issue worldwide, mostly due to the impaired sperm motility. Multiple morphological abnormalities of flagella (MMAF) present aberrant spermatozoa with absent, short, coiled, bent and irregular-calibre resulting in severely decreased Previous studies reported several MMAF-associated genes accounting for approximately half MMAF cases.We conducted genetic analysis using whole-exome sequencing 88 Han Chinese probands. CFAP65 homozygous mutations were identified...
Background Multiple morphological abnormalities of the flagella (MMAF) consistently lead to male infertility due a reduced or absent sperm motility defined as asthenozoospermia. Despite numerous genes recently described be recurrently associated with MMAF, more than half cases analysed remain unresolved, suggesting that many yet uncharacterised gene defects account for this phenotype Methods Exome sequencing was performed on 167 infertile men an MMAF phenotype. Immunostaining and...
Abstract The use of high-throughput sequencing techniques has allowed the identification numerous mutations in genes responsible for severe astheno-teratozoospermia due to multiple morphological abnormalities sperm flagella (MMAF). However, more than half analysed cases remain unresolved suggesting that many yet uncharacterised gene defects account this phenotype. Based on whole-exome data from a large cohort 167 MMAF-affected subjects, we identified two unrelated affected individuals...
Defects in the structure or motility of cilia and flagella may lead to severe diseases such as primary ciliary dyskinesia (PCD), a multisystemic disorder with heterogeneous manifestations affecting primarily respiratory reproductive functions. We report that CFAP61 is conserved component calmodulin- radial spoke-associated complex (CSC) cilia. find splice variant, c.143+5G>A, causes exon skipping/intron retention human, inducing multiple morphological abnormalities (MMAF) phenotype....
Abstract Multiple morphological anomalies of the sperm flagella (MMAF syndrome) is a severe male infertility phenotype which has so far been formally linked to presence biallelic mutations in nine genes mainly coding for axonemal proteins overexpressed flagellum. Homozygous QRICH2 , gene protein known be required stabilizing involved flagellum biogenesis, have recently identified MMAF patients from two Chinese consanguineous families. Here, order better assess contribution etiology...
Intraflagellar transport (IFT) is an evolutionarily conserved mechanism that indispensable for the formation and maintenance of cilia flagella; however, implications functions IFT81 remain unknown. In this study, we disrupted expression in male germ cells starting from spermatocyte stage. As a result, homozygous mutant males were completely infertile displayed abnormal sperm parameters. addition to oligozoospermia, spermatozoa presented dysmorphic nonfunctional flagella. Histological...