The need as indicated by stakeholders. Impaired reproductive performance is a major cause of reduced productivity for ruminants and of reduced profitability for dairy and meat animal producers. The focus of the NE1227 Multistate Project, and its predecessors, NE1027, NE1007, NE161, NE72, NE 41 and NE 1, has been to address nutritional, management and environmental factors that impact ovarian, oviductal, and uterine function, as well as embryo quality, which collectively impact pregnancy rates in domestic ruminants. The long-term goal of the project is to understand how altered ovarian function, impaired oocyte quality, and disruptions of conceptus-uterine interactions contribute to infertility, and devise management strategies that will overcome these factors in order to optimize the chances that animals successfully achieve a pregnancy.  The current proposal will continue this important investigative work, focusing on basic mechanisms that impair or contribute to optimal follicular development, corpus luteum function, oocyte quality, preimplantation embryo development, and uterine-conceptus interactions. Additionally, the feasibility of innovative management practices will be investigated, with development of new strategies based on findings from the basic and applied research. Attaining these goals will positively impact animal producers and the scientific community, as well as indirectly affecting citizens of the region and the nation by promoting sustainable agricultural systems.

The objectives of this proposal align with Strategic Goal 1: Science in the NIFA Strategic Plan (2014-2018). Specifically, they are designed to meet the first sub-goal of Sustainable Agricultural Systems, which “addresses human interaction between science, technology, and agriculture and integrates the biological, physical, and environmental and socioeconomic factors essential to successful production enterprises and viable rural communities”. The success of the project will be measured in part according to NIFA-defined performance measures including (1) Measure 1.1.4 -number of peer-reviewed journal articles, lay publications, patents, and educational activities that increase understanding of biological processes and development of diagnostic techniques; (2) Measure 1.1.10 –behavior change related to factors affecting the decision making process, such as availability of resources and external forces; (3) Measure 1.7.4 –number of college graduates prepared for the professional and technical workforce in the food and agricultural industry; and (4) Measure 1.7.5 –number of graduate students and post-doctorates engaged in NIFA-administered projects and programs with an integrated education component to improve educational opportunities in agriculture.

Importance of work and consequences if it is not done. Improving fertility in ruminants requires fundamental knowledge about internal (e.g. immune cells) and external (e.g. toxins and nutrition) influences on (1) follicle activation, oocyte growth, and oocyte maturation; (2) corpus luteum development, steroidogenesis, and regression; (3) fertilization and preimplantation embryonic development; and (4) conceptus-uterine-ovarian interactions. It is critical to identify the underlying causes of anovulation, fertilization failure, luteal insufficiency, and early embryonic loss in ruminants, which are the leading causes of bovine infertility. By enhancing basic knowledge of the underlying biology surrounding ovarian function and embryonic development, new strategies can be developed for application by producers, veterinarians, and farm consultants. For example, as part of the basic research on follicular development and regulation of corpus luteum function, new reproductive management strategies for first artificial insemination (AI) and rebreeding strategies were developed (Double Ovsynch, optimized voluntary waiting period, extra treatment with prostaglandin F2a during protocols, etc.) and are now in practical use on commercial dairy farms. Studies continue to develop and evaluate management approaches that use already FDA-approved products and novel products in order to provide management strategies that are economical, user- and consumer-friendly, and preserve food quality and safety. Novel nonhormonal strategies, such as supplementation with specific feed additives, have been tested and validated in order to improve reproductive efficiency, reduce pregnancy loss, and improve reproductive health of the animal.

The technical feasibility of the work. The technical members of NE-1227 (molecular biologists, cell physiologists, and animal scientists) are a diverse group of scientists with broad and complementary expertise in ovarian and uterine physiology, oocyte and embryo development, and reproductive management of domestic ruminants. Recent additions of members with expertise in ovarian reserve and activation of follicle growth, preimplantation development of embryos, and maternal recognition of pregnancy will fill important gaps in knowledge in order to more effectively understand factors that cause early embryonic loss in the dairy cow. Previous individual and collaborative productivity of the members are indicative of ability to successfully perform, interpret, and disseminate the specific experiments outlined in the proposal. The diverse nature of the scientists in this project has been one of its strengths, allowing for integration of knowledge to achieve productive management outcomes.

The advantages for doing the work as a multistate effort. Advantages of performing this work as a multistate effort include complementary approaches with collaborative efforts, and technologies that can be integrated and directed toward several objectives simultaneously. The shared experience and data analyses contributed by individuals within the technical group make these interactions more beneficial. Moreover, the combination of basic biological research with innovative applied research more effectively supports outreach programs and engagement, the goal of which is to improve reproductive performance in livestock more rapidly. Using this paradigm, this multistate group has historically been one of the most productive, cohesive, diverse and collaborative multistate research groups nationwide. The commitment of participants to the multistate project is exemplified by numerous collaborative publications, including one in which it was decided to list the project itself as the author, rather than individuals (J. Anim. Sci. 74:1943-1952 [1]). Additionally, members at different stations have contributed to unified animal and cell culture protocols, conducted collaborative experiments, and exchanged samples to take advantage of unique validated procedures and will continue to do so in this project.

Impacts from successfully completing the work. Fulfilling the objectives of this project will provide important new information in order to combat declining fertility among ruminants, and especially dairy cows, in the face of continuous improvement in milk production capability. In the previous project (i.e. NE-1227), proposed research projects were performed using intramural and extramural competitive grant funds garnered by the members (more than $3.6 million). The 15 technical members of NE-1227 published refereed research papers (196), abstracts and conference papers (117), theses and dissertations (27), book chapters and invited reviews (17), technical/extension publications (13), and deposited sequences into the Gene Expression Omnibus (5). In addition, workshops and lectures (13) were presented to producers, veterinarians, and consultants locally and internationally. Based on these outputs, research colleagues investigating reproduction in ruminants around the world developed collaborations and benefited from this multitude of scientific reports and publications.

In addition, veterinarians, consultants, pharmaceutical companies, and breeding organizations who service the agricultural animal industries have been immediate beneficiaries of the work from this project. For example, collaborators have presented annual reports on the project to Select Sires and Genex CRI (Cattle AI organization) and reports at the National Association of Animal Breeders (NAAB). In turn, those groups spread the technology to farm families/producers for implementation, which benefits the on-farm profitability and sustains agricultural production systems that are highly competitive in the global economy.

Student training is another important impact of this project. During the last project period, the 15 technical members submitted more than 80 abstracts to national or international meetings with the bulk of these abstracts presented by graduate students in poster or platform sessions. Furthermore, 37 students completed or are currently pursuing a M.S. or PhD. degree. In addition to graduate students, numerous undergraduate students (98) with an interest in reproductive physiology were introduced to investigative research. These activities represent an important contribution of the project to the education of the next generation of scientists, consultants, and other workers in animal agriculture industries.