Sexually dimorphic genes and early bovine development: impact of environment. – BosexDim

Early mammalian embryo is very sensitive to environmental perturbations, which affect phenotypic traits in a sex-specific manner at adulthood. This assumes that sex-specific differences exist even before hormonal impregnation. Such differences due to sexual chromosomes have been evidenced mainly in the mouse. Yet mouse is special among mammals due to its very early X-chromosome inactivation and high number of inactivated genes. This suggests that sex-related phenotypic differences are even more important in non murine species. BoSeX-Dim project aims to (i) identify early sex-dimorphisms in bovine embryo (ii) analyze how these dimorphisms are modified in response to early embryo environment especially when the embryo is produced in vitro (iii) improve the in vitro conditions for bovine embryo production taking these dimorphic responses into account, to increase selection efficiency in bovine breeding schemes. To reach these ambitious goals the BoSex-Dim consortium gathers skills in bovine developmental biology and high throughput data analysis in this species, heterogeneous high throughput data integration, embryo and reproductive biotechnologies, as well as cattle genomic selection. This will make it possible to integrate data collected at three key developmental stages regarding sexual dimorphism establishment: both before and after X chromosome inactivation and gene dosage compensation have taken place in female embryos/conceptuses, and later on, before hormonal impregnation when fetal gonads are still considered undifferentiated. Novelty of the project relies on integration of heterogeneous data (morphokinetics, metabolome, transcriptome, methylome, and genome) obtained at three different stages, to explore in bovine a still poorly documented but pivotal question for both basic and applied research. Taking into account the scientific knowledge generated in the first part of the project we will improve in vitro culture media to make either male or female in vitro produced embryos closer to their in vivo counterparts. This should increase embryo quality and freezability, thus resulting in a higher efficiency of reproductive biotechnologies and increasing their use in breeding schemes where male and female embryos are differently used. Male embryos are frozen whilst being genotyped and only the best male embryos are then transferred onto recipient cows to produce the next generation elite bulls for artificial insemination. Female embryos are most often transferred fresh for cow replacement. On a basic point of view, knowing how sexual dimorphisms are progressively established paves the way to a better understanding of sex-dimorphic response to environmental perturbations. This will permit to take these sex differences into account in management of cattle pregnancy.