Epigenetic disorders and male subfertility

Abstract: Objective: To provide a link between epigenetics and male subfertility at the DNA, histone-protamine, and RNA levels and its consequences on fertilization and embryo development. Design: Review of the relevant literature. Setting: University-based clinical and research laboratories. Patient(s): Fertile and infertile men. Intervention(s): None. Main Outcome Measure(s): Critical review of the literature. Result(s): Epigenetic markers can be modified in infertile patients. Epigenetic modifications include methylation loss or gain on the global level and on imprinted genes, high levels of histone retention in spermatozoa, and deficiencies in some transcripts involved in spermatogenesis. Interestingly, these abnormalities are all linked together, because DNA methylation maintenance depends on DNA histone-protamine configuration which itself is stabilized by spermatozoal RNAs. Conclusion(s): The paternal genome has long been considered to be silent and passive in embryo formation. The epigenetic processes associated with the paternal DNA genome highlights its importance in male fertility as well as for embryo development

Comparative analysis of global DNA methylation in spermatozoa from fish, molluscs, bird and mammals: effect of cryopreservation

Comparative analysis of global DNA methylation in spermatozoa from fish, molluscs, bird and mammals: effect of cryopreservation. 7. International Workshop on the Biology of Fish Gamete

In vitro exposure to CPF affects bovine sperm epigenetic gene methylation pattern and the ability of sperm to support fertilization and embryo development

Several studies have demonstrated that overexposure to pesticides can reduce mammalian sperm quality, impairing male fertility. Chlorpyrifos (CPF), a widely used organophosphate pesticide, was shown to impair spermatogenesis by inducing the formation of highly reactive toxic intermediates. To gain further insight into the mechanisms underlying the cytotoxicity and genotoxicity of CPF, bovine spermatozoa were exposed in vitro to environmental CPF concentrations and the motility, in vitro fertilization rates, DNA fragmentation, chromatin alterations, and methylation patterns were assessed. Motility and in vitro fertilization rates were significantly reduced in spermatozoa exposed to CPF, while DNA fragmentation and putative chromatin deconstruction appeared to increase at higher pesticide concentrations. In situ hybridization was carried out with X and Y probes on sperm samples exposed to different CPF concentrations, and subsequent analysis highlighted a significant percentage of spermatozoa with a peculiar morphological malformation, in which a narrowing occurred at the level of the hybridization. Analysis of potential abnormalities in the methylation pattern of NESP55-GNAS and XIST promoters displayed no differentially methylated regions in GNAS promoter relative to the control, whereas spermatozoa exposed to 10 μg/mL CPF had increased methylation variance in one region of imprinted XIST promoter. Our results provide support that CPF can induce a genotoxic effect on spermatozoa, impairig their ability to fertilize and support preimplantation embryo development in vitro. These observations are worrying since altered levels of sporadic methylation in genes of male gametes may affect the success of reproduction and contribute to infertility

Developing a toolbox to study the rabbit methylome and its alteration in IUGR cases during gestation

Epigenome is the essential mediator of the effect of environmental exposures on development. Epigenetic studies show that alterations in DNA methylation marks are associated with developmental reprogramming and linked to environmental exposures. Our objective is to develop different Intra Uterine Growth Restriction (IUGR) rabbit models and to study the alterations occurring in the methylome of the placental unit throughout gestation. The relevance of the rabbit model resides in its placentation similarity with humans. As little is known about rabbit epigenome, we are developing a strategy to establish a toolbox to study the rabbit methylome. First, studying the methylome of the placental unit will be performed by MeDIP-seq on pooled samples to generate a methylation overview in both placenta (fetal compartment) and decidua (maternal compartment) at term. In a second time, a microarray will be designed for individual analysis to establish early epigenetic events related to placenta from IUGR. The array design will integrate methylated sequences from MeDIP-seq data but also promoters of differentially expressed genes obtained by transcriptomic analysis performed on the same samples. Finally, to validate our results, methylated regions of interest will be studied by pyrosequencing after bisulfite treatment. The identification of critical epigenetic marks alterations associated with IUGR will allow a better understanding of the IUGR process and an identification of key actors in placental function. In future studies, these marks could be linked to the establishment of a specific phenotype at adulthood and tested as biomarkers at birth to define the risk of developing an adverse phenotype. In addition, this study will present the first overview of the rabbit methylome and lead to the development of epigenomic tools that can be used systematically

Genome-wide analysis of DNA methylation in clones and nonclones of two different breeds: Holstein and Japanese black

National audienc

Levels of fecal glucocorticoid metabolites do not reflect environmental contrasts across islands in black-tailed deer (Odocoileus hemionus sitkensis) populations

International audienceAnimals face stressful situations to which they can respond by mounting a physiological response. Few studies have compared the relative effects of two or more stressors on this response. We compared how low food abundance and hunting affected levels of fecal glucocorticoid metabolites (FGM), an indicator of stress, in Sitka black-tailed deer (Odocoileus hemionus sitkensis) on the Haida Gwaii archipelago (Canada). We monitored monthly FGM levels over a year on three islands: on two, there was no hunting but deer were exposed to increased risk of severe food depletion; and on one, deer had access to abundant food but were exposed to a few days of hunting each year. Based on the context of the study, we tentatively predicted that FGM levels would be higher in low food abundance/safe islands. We also predicted that FGM levels would be higher in winter when food is rarer, particularly in low food abundance/safe islands. The three deer populations presented similar average FGM levels and seasonal variations. Our predictions were therefore not supported. Our results rather suggested that environmental contrasts, perceived by us as large (increased risk of starvation on ELI and Kunga islands) or associated with differences in animal behavior (human avoidance on Reef island), did not lead to increased stress responses. We discuss plausible explanations, including the down-regulation of the stress response in depleted environments and the lack of stress response to low hunting pressure when behavioral responses to risk are unlikely to be costly