Early embryonic development
Preimplantation embryo stage is an essential tool for many areas of biotechnology, such as those used in animal production, assisted reproduction, production of stem cells for cell therapy, transgenic animal production, conservation of germplasm, etc. At the same time is a unique tool for understanding mechanisms of genetic and epigenetic reprogramming that occurs not only during the preimplantation development, but also in other processes like the formation and differentiation of stem cells, tumor formation and aging, as well as derivatives of certain technologies such as transgenesis and nuclear transfer. The unit is pioneer in the transcriptomic and epigenomic analysis of preimplantation embryos in animals’ models and farm animals, with the objective of improve the techniques of embryo manipulation and to produce viable embryos with greater efficiency and quality. We are also analyzing the genetic and epigenetic reprogramming that occurs during the formation and differentiation of embryonic stem cells and in reprogramming adult cells to inducible stem cells. We are pioneers in the development of new techniques for transgenesis. We are also analyzing how alteration in early developmental networks can expose otherwise buffered stochastic variability in gene expression, leading to pronounced phenotypic variation (both in animal production traits as the origin of adult diseases).
Gametogenesis, sperm selection and ART
We use embryonic micromanipulation and transgenesis techniques to analyze genes that affect gametogenesis, to improve the technologies applied in assisted reproduction in production animals, and to ensure the efficacy and safety of embryonic micromanipulation techniques. Of the millions of sperm in an ejaculate, only a few dozen go up to the oviductal ampulla, where the oocytes are fertilized. Using animal models, we have determined that in vitro thermotaxis selects capable sperm, with intact DNA, and improves blastocyst production and live animals, and we are optimizing the technique for use in other mammalian species. We also use transgenic animals with mutations in candidate genes to participate in gametogenesis and / or fertilization, which allow us to design new fertility diagnostic markers and understand the molecular mechanisms responsible for these processes.
Role of splicing in reproduction
In livestock, implantation failure, male fertility and sex determination are some of the most important factors affecting animal production; but little genetic progress has been achieved by traditional selection schemes due to the complex genetic architecture of these reproductive traits, and because functional genomic data are processed at the gene level, losing the information that could be extracted from the analysis of isoforms. Nevertheless, developmental complex process are usually regulated through transcriptional and post-transcriptional regulatory mechanisms; among the latter, alternative splicing (AS) is the most prevalent in mammals, with over 90% of mammals genes being alternatively spliced, producing different isoforms with possible different functions. The aim of this research is to study the role that AS plays in these processes, study the functionality of different isoforms that we have previously identify as specific components in the sex determination of mice and cattle, and analyze the functionality of several genetic variants unravels by genomic studies that affect bull fertility. Identification and functionality analysis of isoforms generated by AS affecting early development, sex determination and male fertility traits is crucial for improving breeding efficiency, reproductive performance and sustainability of farm animals. In addition, these results will provide the first insights into how splicing affects pluripotency and early embryo development, and how reduction of some isoforms in the Y-chromosome could affect the sex ratio of the offspring, strategy that would allow us to select the sex in the farm animals according to the needs, and to produce laboratory animals of the desired sex, avoiding the sacrifice of animals of a sex that were not to be used.