The Sperm Olfactory Receptor OLFR601 is Dispensable for Mouse Fertilization

11 Pág. Departamento de Reproducción Animal​ (INIA)Fertilization involves the fusion of two gametes by means of yet unknown membrane binding and fusion events. Over the last years, many sperm proteins have been uncovered to play essential roles in sperm-egg fusion in mammals, but their precise role in fertilization remains unknown, being unclear how these proteins interact with each other or with other yet unknown sperm proteins. The aim of this study has been to identify possible sperm proteins interacting with TMEM95, a protein essential for fertilization located in the sperm membrane. A list of 41 sperm proteins that were pulled down with TMEM95 and identified by mass spectrometry did not include other sperm proteins known to play a role in fertilization, suggesting an independent role of TMEM95 in fertilization. Between these lists, OLFR601 is allocated to the acrosomal region and may mediate affinity for an odorant involved in fertilization. However, Olfr601 disruption did not impair the sperm fertilization ability, suggesting that its function may be redundant with that of other sperm proteins.This work was supported by the projects AGL 2017-84908-R and PID 2020-117501RB-I00 to B-AP and PID 2020-114109GB-I00 to J-MM, funded by the Spanish Ministry of Science and Innovation and FEDER funds from the European Union.Peer reviewe

TMEM95 is a sperm membrane protein essential for mammalian fertilization

The fusion of gamete membranes during fertilization is an essential process for sexual reproduction. Despite its importance, only three proteins are known to be indispensable for sperm-egg membrane fusion: the sperm proteins IZUMO1 and SPACA6, and the egg protein JUNO. Here we demonstrate that another sperm protein, TMEM95, is necessary for sperm-egg interaction. TMEM95 ablation in mice caused complete male-specific infertility. Sperm lacking this protein were morphologically normal exhibited normal motility, and could penetrate the zona pellucida and bind to the oolemma. However, once bound to the oolemma, TMEM95-deficient sperm were unable to fuse with the egg membrane or penetrate into the ooplasm, and fertilization could only be achieved by mechanical injection of one sperm into the ooplasm, thereby bypassing membrane fusion. These data demonstrate that TMEM95 is essential for mammalian fertilization

Pluripotent stem cells related to embryonic disc exhibit common self-renewal requirements in diverse livestock species

This is the author accepted manuscript. The final version is available from Palgrave Macmillan via the DOI in this record Data Availability: RNA-seq data generated in this study are deposited in Gene Expression Omnibus under accession number GSE172420 (reviewer token wjevsgycnnafbub).Despite four decades of effort, robust propagation of pluripotent stem cells from livestock animals remains challenging. The requirements for self-renewal are unclear and the relationship of cultured stem cells to pluripotent cells resident in the embryo uncertain. Here, we avoided using feeder cells or serum factors to provide a defined culture microenvironment. We show that the combination of activin A, fibroblast growth factor and the Wnt inhibitor XAV939 (AFX) supports establishment and continuous expansion of pluripotent stem cell lines from porcine, ovine and bovine embryos. Germ layer differentiation was evident in teratomas and readily induced in vitro. Global transcriptome analyses highlighted commonality in transcription factor expression across the three species, while global comparison with porcine embryo stages showed proximity to bilaminar disc epiblast. Clonal genetic manipulation and gene targeting were exemplified in porcine stem cells. We further demonstrated that genetically modified AFX stem cells gave rise to cloned porcine foetuses by nuclear transfer. In summary, for major livestock mammals, pluripotent stem cells related to the formative embryonic disc are reliably established using a common and defined signalling environment.Biotechnology and Biological Sciences Research CouncilBiotechnology and Biological Sciences Research CouncilEuropean Research CouncilMedical Research CouncilMedical Research CouncilJapan Society for the Promotion of ScienceJapan Society for the Promotion of ScienceJapan Agency for Medical Research and DevelopmentJapan Agency for Medical Research and DevelopmentWellcome TrustMedical Research Counci

Intergenerational transmission of the positive effects of physical exercise on brain and cognition

Physical exercise has positive effects on cognition, but very little is known about the inheritance of these effects to sedentary offspring and the mechanisms involved. Here, we use a patrilineal design in mice to test the transmission of effects from the same father (before or after training) and from different fathers to compare sedentary- and runner-father progenies. Behavioral, stereological, and whole-genome sequence analyses reveal that paternal cognition improvement is inherited by the offspring, along with increased adult neurogenesis, greater mitochondrial citrate synthase activity, and modulation of the adult hippocampal gene expression profile. These results demonstrate the inheritance of exercise-induced cognition enhancement through the germline, pointing to paternal physical activity as a direct factor driving offspring’s brain physiology and cognitive behavior.We thank Cesar Cobaleda [Centre of Molecular Biology Severo Ochoa (CBMSO), Spanish National Research Council/Autonomous University of Madrid (CSIC/UAM), Madrid, Spain] and Alberto González-de la Vega (MegaLab, Madrid, Spain) for expert assistance and advice of the RNAseq, DAVID, and GSEA analysis; María Llorens-Martín (CBMSO, CSIC/UAM, Madrid, Spain) for useful discussions; Silvia Fernández (Cellular and Molecular Biology Unit, Cajal Institute, Madrid, Spain) and Laude Garmendia (Animal House, Cajal Institute, Madrid, Spain) for volunteer help and advice; the Image Analysis Unit of the Cajal Institute; Carmen Sandi (Brain Mind Institute, Lausanne, Switzerland) for helpful and useful advice and assistance; and all members of the National Centre for Biotechnology Mouse Embryo Cryopreservation Facility— María Jesús del Hierro, Marta Castrillo, and Lluís Montoliu—for their huge efforts and impressive involvement in the IVF experiments. This work was supported by the Spanish Ministry of Economy and Competitiveness Project Grants BFU2013-48907-R and BFU2016-77162-R (to J.L.T.), SAF2016-78845-R (to S.R.F.), RYC-2012-10193 and AGL2014-85739-R (to P.B.Á.), CP14/00105 and PI15/00134 (to A.M.-M.); by the Instituto de Salud Carlos III of the Spanish Ministry of Economy and Competitiveness; and by the European Regional Development Fund Grant PT17/0009/0019 (to A.E.-C). Á.F.-L. was funded by a CSIC JAE-Doc Programme grant and VPlan Propio US-Acceso Grant, I.L.-T. was funded by a predoctoral fellowship (FPI) grant, and K.R.M. was funded by a contract associated with the above-mentioned project grants awarded to J.L.T

Invasive Species Control and Resolution of Wildlife Damage Conflicts: A Framework for Chemical and Genetically Based Management Methods

Vertebrate wildlife damage management relates to developing and employing methods to mitigate against damage caused by wildlife in the areas of food production, property damage, and animal or human health and safety. Of the many management tools available, chemical methods (e.g., toxicants) draw the most attention owing to issues related to environmental burden, species specificity, and humaneness. Research and development focusing on RNA interference and gene drives may be able to address the technical aspects of performance goals. However, there remain many questions about regulation, environmental risk, and societal acceptance for these emerging biological technologies. Here we focus on the development and use of these biological technologies for use in vertebrate pest management and conservation (e.g., management of wildlife diseases). We then discuss the regulatory framework and challenges these technologies present and conclude with a discussion on factors to consider for enabling these technologies for pest management and conservation applications under a commercially applied framework