Reference number : GC-2017-Q1-02865, amendment number : , agreement type : G, recipient legal name : Manjunath, Puttaswamy (Université de Montréal), recipient country : CA, recipient province : nan, recipient city : Quebec|Québec, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : Canada exported more than 110 million dollars worth of bull semen to over 100 countries in 2015 (Agriculture Canada). This represents &gt;20% of world export of bull semen. The most commonly used protective agents to conserve mammalian sperm contain 20% egg yolk (EY) in Tris-/citrate buffers or skimmed/whole milk and 6-7% glycerol. This basic constituent of sperm preservation media (also called diluters or extenders) has remained the same since the practice of artificial insemination was introduced some 70 years ago. EY and milk being products of animal origin represent a potential risk of transmission of diseases. Thus, there is an urgent need for developing synthetic extenders, which are free of products of animal origin. To achieve this goal, it is essential to understand the molecular mechanisms involved in this phenomenon. Our pioneering work discovered that most ungulates (bull, stallion, ram, goat, bison, boar) semen contains Binder of Sperm (BSP) proteins in high magnitude. These BSPs, essentially secreted by seminal vesicles and added to sperm at ejaculation, bind to the sperm membrane. We identified the binding sites on sperm membranes as phosphatidylcholine . In further studies, we discovered that these BSPs upon binding to sperm membranes extract lipids, which makes sperm sensitive to cryopreservation. Interestingly, BSPs also interact with low-density lipoproteins (LDL) , the main constituents of EY extenders. While these BSPs bind to sperm, they extract lipids from the membrane and exert the detrimental effect on sperm, but when BSPs associate with LDL, the detrimental effect on sperm is subdued and sperm are protected. Thus, the sequestration of BSPs by extender components appears to be the basis of sperm protection . Additionally, we hypothesized that the synthetic substances bearing choline or pseudo-choline groups such as diethylaminoethyl (DEAE) groups may mimic EY, sequestrate BSPs and protect sperm during conservation . Preliminary studies now indicate that dextrans coupled with DEAE groups, bind BSPs and this interaction preserve sperm functions just like EY. Thus, the short-term objective of the present program is to identify the dextran derivative (among four candidates) having the highest affinity for BSPs and to examine the effect on bull sperm functions (post-thaw) and on in vitro fertilization. The basic studies proposed in this program are original, unique in the world and will further the understanding of the molecular mechanisms of sperm preservation with extenders. In the long-term, our work has technological impact and promises to develop pathogen-free and environmentally friendly novel extenders for semen storage (in the liquid or frozen state) for artificial insemination and animal reproduction applications in Canada and abroad. HQPs trained in this program have high potential to get jobs in semen processing industries or in the fertility clinics ., program purpose french : Canada exported more than 110 million dollars worth of bull semen to over 100 countries in 2015 (Agriculture Canada). This represents &gt;20% of world export of bull semen. The most commonly used protective agents to conserve mammalian sperm contain 20% egg yolk (EY) in Tris-/citrate buffers or skimmed/whole milk and 6-7% glycerol. This basic constituent of sperm preservation media (also called diluters or extenders) has remained the same since the practice of artificial insemination was introduced some 70 years ago. EY and milk being products of animal origin represent a potential risk of transmission of diseases. Thus, there is an urgent need for developing synthetic extenders, which are free of products of animal origin. To achieve this goal, it is essential to understand the molecular mechanisms involved in this phenomenon. Our pioneering work discovered that most ungulates (bull, stallion, ram, goat, bison, boar) semen contains Binder of Sperm (BSP) proteins in high magnitude. These BSPs, essentially secreted by seminal vesicles and added to sperm at ejaculation, bind to the sperm membrane. We identified the binding sites on sperm membranes as phosphatidylcholine . In further studies, we discovered that these BSPs upon binding to sperm membranes extract lipids, which makes sperm sensitive to cryopreservation. Interestingly, BSPs also interact with low-density lipoproteins (LDL) , the main constituents of EY extenders. While these BSPs bind to sperm, they extract lipids from the membrane and exert the detrimental effect on sperm, but when BSPs associate with LDL, the detrimental effect on sperm is subdued and sperm are protected. Thus, the sequestration of BSPs by extender components appears to be the basis of sperm protection . Additionally, we hypothesized that the synthetic substances bearing choline or pseudo-choline groups such as diethylaminoethyl (DEAE) groups may mimic EY, sequestrate BSPs and protect sperm during conservation . Preliminary studies now indicate that dextrans coupled with DEAE groups, bind BSPs and this interaction preserve sperm functions just like EY. Thus, the short-term objective of the present program is to identify the dextran derivative (among four candidates) having the highest affinity for BSPs and to examine the effect on bull sperm functions (post-thaw) and on in vitro fertilization. The basic studies proposed in this program are original, unique in the world and will further the understanding of the molecular mechanisms of sperm preservation with extenders. In the long-term, our work has technological impact and promises to develop pathogen-free and environmentally friendly novel extenders for semen storage (in the liquid or frozen state) for artificial insemination and animal reproduction applications in Canada and abroad. HQPs trained in this program have high potential to get jobs in semen processing industries or in the fertility clinics ., agreement title english : Mechanism of mammalian sperm protection by extender components and development of novel extenders free of products of animal origin, agreement title french : Mechanism of mammalian sperm protection by extender components and development of novel extenders free of products of animal origin, agreement number : RGPIN, agreement value : 140000.0, agreement start date : 2017-05-10, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023), additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023), owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada