Investigation
Our research lines are the following
Conceptus elongation in ungulates
Conceptus elongation is a developmental process
occurring in embryos from ungulates (cows, sheep, goats and pigs, among others).
Failures in this process are the
main cause of embryonic loss and, thereby, of infertility in these species, causing
great economic losses in the livestock industry.
Gastrulation takes place during this process developing a flat embryonic disc
very similar to that of humans, so ungulates constitute a closer model to humans than mice. Diverse
congenital disorders such as spina bifida are caused by gastrulation failures.
Understanding the processes involved in elongation/gastrulation is required to avoid embryonic losses and developmental disorders.
We account on
European funds (ERC, https://cordis.europa.eu/project/id/757886) ) to study this process by gene editing and in vitro approaches.
We use
CRISPR technology to ablate genes in bovine embryos in order to understand their function on conceptus elongation.
We also perform
metabolomics and proteomics analyses in the uterine fluid where embryos develop to understand their metabolic and signalling requirements.
We have developed an
in vitro system that allows bovine and ovine embryo development beyond the blastocyst stage, an unprecedented advance in any livestock species (Ramos-Ibeas et al. Reproduction 2020).
Study of reproductive processes in livestock species by CRISPR technology
Gene ablation (KO) allows to unequivocally elucidate the function of a given gene in a biological process.
The laboratory mouse has been the most employed mammalian model for that purpose, as it was the only species where KO animals could be easily generated. Nevertheless, mice are not a valid model to study some particular processes in livestock species or humans.
Using CRISPR technology we can now generate KO animals and other genetically modified models (KI) in other mammalian species.
We generated the
first gene edited livestock animals in Spain (KO rabbits for the gene ZP4) uncovering the role of the only protein of the zona pellucida (ZP4) whose function remained unclear, as it was absent in mice.
ZP4 plays an essential structural role: without ZP4, the zona pellucida fails to protect the embryo, that dies before implantation (Lamas-Toranzo et al. eLife 2019).
We also generate KO murine models when mice are a suitable model to study a particular process. For instance, we have generated KO mice for Tmem95, uncovering the essential role of this protein in fertilization.
TMEM95-null sperm are unable to penetrate into the oocyte, becoming
the third sperm protein known to be essential for fertilization (Lamas-Toranzo et al. eLife 2020).
We keep generating KO models to study other reproductive processes or collaborating with other groups working in other fields. We account on
funds from the Spanish Ministry of Science and Universities (AGL2017-84908-R).
Development of CRISPR technology for gene editing in livestock species
The above-mentioned applications would not have been achievable without the optimized protocols for gene edition by CRISPR in livestock species developed under
previous projects (AGL2014-58739-R and RYC-2012-20193).
We have developed protocols to boost the efficiency of KO (Lamas-Toranzo et al. Sci Rep 2019) and KI (Lamas-Toranzo et al. Mol Reprod Dev 2020) generation.
We are
authorized by the Spanish National Biosafety Agency to generate genetically modify mice, rabbits, goats and sheep in our facilities.
Molecular markers of oocyte competence
We are evaluating the predictive value of diverse parameters in cumulus cells on the developmental potential of the oocyte, aiming to
improve fertility rates following Assisted Reproduction Techniques in humans and animals. This research is funded by an
Industrial PhD project from Madrid Region government (IND2017/BIO-7748).
We are
authorized by the Spanish National Biosafety Agency to generate genetically modified mice, rabbits, goats and sheep in our facilities.
Offspring sex control in livestock species
Our group has a long publication and technology transfer record on the use of sex sorted semen and embryo sexing in cattle.
