Publications by authors named "Pierre Ray"
Purpose: To evaluate ovarian stimulation response in couples undergoing preimplantation genetic testing (PGT-M) for myotonic dystrophy type 1 (DM1) METHODS: Retrospective, observational, multicentric study. Parameters of ovarian response and PGT-M outcomes were compared according to the DM1-affected patient (female or male). A total of 229 couples underwent at least one controlled ovarian hyperstimulation cycle for the PGT-M procedure.
View Article and Find Full Text PDFAsthenoteratozoospermia is a common cause of male infertility. To further define the genetic causes underlying asthenoteratozoospermia, we performed whole-exome sequencing in a cohort of Han Chinese men with asthenoteratozoospermia. Homozygous deleterious variants of MYCBPAP were first identified in two unrelated Chinese cases.
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- Small RNAs, particularly piRNAs, are essential for male germ cell development, with disruptions leading to male infertility through issues like spermatogenic defects and oligo-astheno-teratozoospermia (OAT).
- The HENMT1 gene is critical for the biogenesis of piRNAs, and its dysfunction can cause severe sperm abnormalities and infertility, as seen in both knockout mice and patients with HENMT1 variants.
- The study aimed to explore the potential for using sperm from two patients with HENMT1 variants in assisted reproductive technologies, but despite thorough analyses and multiple IVF-ICSI attempts, no live births were achieved.
Article Synopsis
- Non-obstructive azoospermia (NOA) from primary spermatogenic failure is a severe male infertility issue with limited treatment options, and genetic testing can help predict outcomes for procedures like testicular sperm extraction (TESE).
- A study using whole-genome sequencing on an Iranian family revealed a harmful variant in the TDRKH gene, which is crucial for male fertility; its absence leads to sperm production failures similar to findings in Tdrkh knockout mice.
- This research reinforces the importance of the piRNA pathway in spermatogenesis and indicates that men with TDRKH variants have a high likelihood of complete spermatogenic arrest, similar to previously studied North African cases.
Article Synopsis
- - A study involving 167 infertile patients identified bi-allelic mutations in the CCDC146 gene, linked to a condition known as multiple morphological abnormalities of the flagellum (MMAF) affecting sperm structure.
- - Researchers developed a knock-out mouse model, which showed that male mice lacking CCDC146 were infertile and had sperm characteristics similar to those of the mutated patients.
- - CCDC146 is important for the proper formation of sperm structures like the axoneme and other microtubule-related organelles, highlighting its role as a microtubule inner protein (MIP) that can lead to infertility when mutated.
Article Synopsis
- Sperm flagella and motile cilia share a similar microtubule structure, and issues with these structures can lead to male infertility, manifesting as isolated conditions or syndromes like Primary Cilia Dyskinesia (PCD).
- Two unrelated patients with multiple morphological abnormalities of sperm flagella (MMAF) were found to have distinct mutations in the PCD gene CCDC65, which leads to a significant decrease in its protein in sperm.
- This research demonstrates that CCDC65 is essential for sperm flagellum structure and suggests that mutations in this gene can cause asthenozoospermia, a condition characterized by reduced sperm motility.
Article Synopsis
- Motile cilia and flagella are important organelles involved in movement and are made up of a complex structure called the axoneme, which relies on proteins from numerous genes; defects in these genes can lead to primary ciliary dyskinesia (PCD).
- In a study of 196 infertile men with a specific sperm flagella abnormality known as multiple morphological abnormalities of the flagella (MMAF), researchers identified a harmful variant in the GAS8 gene linked to male infertility.
- The study found that the GAS8 variant disrupts the structure and function of the Nexin-Dynein Regulatory Complex (N-DRC), causing misalignment of microtubules in sperm flagella and resulting in
Article Synopsis
- * Researchers discovered homozygous variants linked to the condition in four unrelated patients, which disrupted the localization of certain proteins essential for sperm flagellum function.
- * The study identified ZMYND12 as a new gene associated with asthenoteratozoospermia, which forms a complex with other proteins critical for sperm motility, affecting male fertility.
Article Synopsis
- The study investigates whether men with specific ultrastructural defects in sperm flagella have lower success rates in intracytoplasmic sperm injection (ICSI) and worse outcomes for pregnancies and newborns.
- A retrospective analysis of 189 ICSI cycles from men with three types of flagellar defects (DFS, PFD, NSFA) was conducted, comparing their outcomes with a control group.
- Results showed no significant negative impact of these defects on fertilization, pregnancy, or delivery rates, indicating generally favorable outcomes despite the presence of flagellar abnormalities.
Article Synopsis
- Sperm fertilization depends on effective movement through the female reproductive system and a process called capacitation, which is influenced by specific signaling pathways.
- Researchers studied an infertile patient with poor sperm motility and found harmful genetic variants affecting proteins related to sperm function.
- The study reveals that these genetic mutations impair sperm's ability to undergo necessary chemical changes for successful fertilization and identifies a crucial protein, IQCH, essential for sperm movement and capacitation.
Reproduction involves a wide range of biological processes, including organ formation and development, neuroendocrine regulation, hormone production, and meiosis and mitosis. Infertility, the failure of reproduction, has become a major issue for human reproductive health and affects up to one in seven couples worldwide. Here, we review various aspects of human infertility, including etiology, mechanisms, and treatments, with a particular emphasis on genetics.
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- Reciprocal translocation (RT) carriers have a higher risk of infertility, miscarriages, and children with health issues due to the production of unbalanced gametes.
- Prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) can help minimize these risks, but there are concerns about the effectiveness of sperm fluorescence in situ hybridization (spermFISH) as a diagnostic tool for RT carriers.
- A study of 41 RT carriers indicated that acrocentric chromosomes lead to more unbalanced gametes, and the variability in balanced sperm rates suggests that using spermFISH routinely may not be beneficial for these patients.
Primate-specific genes (PSGs) tend to be expressed in the brain and testis. This phenomenon is consistent with brain evolution in primates but is seemingly contradictory to the similarity of spermatogenesis among mammals. Here, using whole-exome sequencing, we identified deleterious variants of X-linked SSX1 in six unrelated men with asthenoteratozoospermia.
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- Male infertility, specifically the MMAF phenotype, involves severe sperm flagellum defects linked to multiple genetic factors, with around 40 known associated genes.
- In a study of 167 MMAF patients, researchers identified new pathogenic mutations in the DNHD1 gene, previously recognized for its role in this condition, highlighting its crucial function for sperm flagellum structure.
- Advanced imaging techniques confirmed significant abnormalities in sperm cells from mutated patients, reinforcing the importance of understanding these genetic mutations for diagnosing unexplained cases of male infertility.
Treatment of Mouse Sperm with a Non-Catalytic Mutant of PLA2G10 Reveals That PLA2G10 Improves In Vitro Fertilization through Both Its Enzymatic Activity and as Ligand of PLA2R1.
Roland Abi Nahed Magali Dhellemmes Christine Payré Emilie Le Blévec Jean-Philippe Perrier Pierre F Ray
Int J Mol Sci
July 2022
Article Synopsis
- - The enzyme phospholipase A2 (PLA2G10) enhances the acrosome reaction in mouse sperm, improving fertilization rates, and its action involves an autocrine feedback loop where it amplifies its own secretion.
- - In IVF studies, sperm from mice lacking PLA2G10 produced fewer embryos, but adding recombinant PLA2G10 could restore fertility; the catalytic activity of PLA2G10 is crucial, as shown by how inhibitors affect fertility outcomes.
- - The mutated form of PLA2G10, which has low enzymatic activity but binds well to the receptor PLA2R1, shows varying effects on fertility depending on the mouse strains used, indicating that PLA2G10's role in
Article Synopsis
- The study introduces a compact 3D diffractive microscope designed for long-term observation of developing organisms within a cell incubator without moving parts, making it easy to use with standard cell culture containers.
- The microscope images large specimens (over 100µ in size) at subcellular resolution by reconstructing optical properties using intensity-only images taken from various angles with an LED array, aided by a deep-learning neural network.
- This technology was successfully applied to time-lapse 3D imaging of preimplantation mouse embryos over six days, allowing for detailed insights into embryo development and viability without the need for labels.
Article Synopsis
- * Four genes linked to OMD are PATL2, TUBB8, WEE2, and ZP1, with recent studies identifying patients carrying defects in these genes, including a novel ZP1 variant affecting oocyte quality.
- * Whole exome sequencing in a North African cohort revealed that 44% of OMD patients could be diagnosed, highlighting the significant role of genetic testing in understanding female infertility.
Male infertility is an important health concern that is expected to have a major genetic etiology. Although high-throughput sequencing has linked gene defects to more than 50% of rare and severe sperm anomalies, less than 20% of common and moderate forms are explained. We hypothesized that this low success rate could at least be partly due to oligogenic defects - the accumulation of several rare heterozygous variants in distinct, but functionally connected, genes.
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- * This study focuses on enhancing the genetic understanding of NOA by identifying new genes linked to the condition through exome sequencing of 96 individuals who previously tested negative for routine genetic abnormalities.
- * Researchers found potentially causative genetic defects in 16 genes across 22 individuals, with a clear correlation between defects in meiotic genes and unsuccessful sperm retrieval, suggesting that genetic testing could help predict surgical outcomes for patients.
Article Synopsis
- In a case study of a man with severe oligozoospermia and a misdiagnosed macrozoospermia, no harmful variants were found in the AURKC gene, prompting the use of WES which identified a harmful variant in the ZMYND15 gene.
- The study confirms that bi-allelic variants in ZMYND15 can cause severe oligozoospermia and may lead to misdiagnosis, emphasizing the importance of using comprehensive genetic testing methods like WES when looking for sperm defect causes.
Article Synopsis
- * Researchers identified two rare loss-of-function variants in testis-specific genes through whole exome sequencing and verified their role using CRISPR/Cas9 to create knockout mice.
- * The knockout mice exhibited normal fertility and sperm parameters, suggesting that the studied genes may not be essential for spermatogenesis, challenging previous assumptions about their role in male fertility.
Article Synopsis
- - Defects in cilia and flagella can lead to serious health issues like primary ciliary dyskinesia (PCD), impacting mainly the respiratory and reproductive systems.
- - A splice variant of the CFAP61 gene, linked to multiple morphological abnormalities of flagella (MMAF), was identified, and knockout mouse models exhibited infertility consistent with this mutation but lacked symptoms typical of PCD.
- - The study shows that CFAP61 is crucial for the stability and structure of flagella, particularly in male reproductive cells, highlighting a specific mechanism that contributes to male infertility.
Article Synopsis
- The study investigates whether ICSI (intracytoplasmic sperm injection) outcomes are negatively affected in men with severe asthenozoospermia combined with multiple morphological abnormalities of the flagellum (MMAF).
- Results indicate that ICSI success for couples with MMAF is comparable to that of other infertile couples, despite some technical challenges encountered.
- The research involved a retrospective analysis of 25 infertile men diagnosed with MMAF, using advanced techniques to assess sperm structure and genetic causes, ultimately treating 20 couples with ICSI.