Research Project: Improving Lifetime Productivity in Swine

Location: Livestock Bio-Systems

2018 Annual Report

Objectives
Objective 1: Improve swine production by identifying factors contributing to prenatal piglet development and survival and postnatal preweaning mortality. Subobjective 1.A: Improve conceptus, postnatal, and preweaning survival by determining early pregnancy factors contributing to variation in fetal and postnatal development. Subobjective 1.B: Increase piglet production by discovering fetal and postnatal development features that are influenced by uterine capacity. Subobjective 1.C: Determine the influence of placental membrane transporters on placental and fetal development. Objective 2: Increase productivity and longevity of replacement gilts by identifying and defining physiological and environmental factors underlying developmental and reproductive processes. Subobjective 2.A: Improve strategies for selecting gilts by defining environmental, physiological, and metabolic factors responsible for variation in growth and reproductive efficiency. Subobjective 2.B: Reduce failure of gilt retention through discovery of gene pathways and their interaction with physiological and environmental factors affecting the phenotypic expression of pubertal traits. Objective 3: Enhance sow performance and retention within the breeding herd by identifying physiological and environmental features at critical periods throughout life that contribute to production and longevity. Subobjective 3.A: Identify behavioral and environmental factors during gestation, lactation, or post-weaning periods to develop feeding strategies that improve sow reproductive performance and longevity. Subobjective 3.B: Discover factors (microbiome profiles, metabolites, transcripts, proteins, and/or genes) within tissues or biofluids from female breeding stock for use in genomic, metabolomic, or microbiome studies to improve reproductive efficiency, piglet production, and sow longevity.

Approach
Maximizing lifetime productivity of swine is essential to meet the ARS Grand Challenge of a 20% increase in production and a 20% reduction in environmental impact by 2025 and is a high priority research initiative of the pork industry. Lifetime productivity of swine is an extremely complex trait and our understanding of the biological mechanisms that underlie the trait or its component traits is limited. Increasing our knowledge and basic understanding of development, growth, and maintenance at all levels of swine production will impact lifetime productivity. The overarching goal is to discover physiological, metabolic, and environmental factors affecting fetal survival, piglet growth, reproductive development, and sow productivity and longevity. This will be accomplished by combining transcriptomics, metabolomics, microbiomics and other molecular biology techniques with genetic and physiological studies at the farm level. Our first objective will focus on conceptus through neonate to produce more consistent-sized, healthy piglets, subsequently reducing pre-weaning mortality and improving growth rates. Secondly, we will identify factors that contribute to young females that have greater success entering and staying in the breeding herd. Our final objective will investigate environmental and energy dynamics of mature females relating these to production and longevity. The tools and strategies developed from this project will be used to improve pork production efficiency. Maximizing lifetime productivity of swine will enhance the welfare and well-being by minimizing fetal and neonatal death, and reducing unnecessary culling of gilts and sows. Application of these results will increase the economic competitiveness of U.S. pork producers.

Progress Report
Subobjective 1A. We began to collect blood samples at the end of January 2018. As of July 16, 2018, we have collected plasma samples on 496 females and performed progesterone analysis on 270 of these plasma samples. The project will continue through December 2019. Subobjective 1B. We have initiated Exp. 1 of this objective and collected pregnancy information on two excess bred gilts. It has been more difficult to obtain excess bred gilts as we are currently limited on the number of replacement animals as a result of a porcine reproductive respiratory syndrome (PRRS) outbreak in November 2017 and requirements of female pigs for other projects. Subobjective 1C. This project has been suspended indefinitely due to limitations in excess replacement gilts due to a PRRS outbreak in November 2017 and requirements of females for other projects. Subobjective 2A. This objective has proceeded as expected. We have continued to collect phenotypic data on gilts that move through the feed efficiency barn. Phenotypic data has been added to the database. Blood samples for metabolomics have been collected. Processing metabolomic samples will begin in the fall. Subobjective 2B. We have continued to collect pubertal phenotypes to add to the database. Phenotypic data from 1,029 noncycling and cycling littermate control gilts has been entered into the database. Tissues for RNAseq analysis in the discovery population have been collected. RNA-Seq libraries were constructed from arcuate nucleus (ARC) and major olfactory epithelium (MOE) from gilts not showing estrus at 240 days and normal gilts displaying estrus (controls). Nonestrus gilts were subdivided into delayed puberty (no ovulation events) and behavioral anestrus (no estrus with ovulation event). Differential gene expression (DGE) showed only a small number of genes differentially expressed between nonestrus gilts and controls, while normal cycling gilts had over 2,800 genes differentially expressed depending upon their stage of the estrus cycle. Over 18,000 genes were expressed in the MOE at measurable levels. Analysis of differently expressed gene (DEG) in the ARC is currently underway. Iso-seq sequencing was completed on MOE and arcuate nucleus from noncycling gilts and controls. These data will be added to the Functional Annotation of Animal Genomes (FAANG) data base. Subobjective 3B. We have initiated the collection of DNA from milk samples using the Mo-Bio PowerFood DNA isolation kit. Upon completing DNA isolation, libraries will be prepared and sequenced. A scientist at University of Tennessee is awaiting the sequence data to begin analyzing the microbial profile.

Accomplishments
1. In swine, first-time mothers have increased tissue mobilization and metabolic signaling to increase feed intake. The period in which a sow is nursing a litter of piglets is very energetically demanding. In particular, young sows nursing their first litter are more susceptible to these demands and will respond differently than mature sows. Research by ARS scientists at Clay Center, Nebraska found that blood chemical profiles suggest first-time sows utilize body tissue reserves to support nursing and recovery while receiving chemical signals to increase feed intake. Of great interest, plasma lactate and creatine levels in first-time mothers became elevated shortly after farrowing and remained elevated through weaning, while creatinine, a by-product of creatine, decreased through weaning. Decreased levels of creatinine indicates the animal was maintaining the creatine for use in energy metabolism instead of converting it to a by-product for removal. Increased levels of lactate may be working in concert with creatine to assist with rebuilding skeletal muscle mobilized for milk production. Simultaneously, lactate could also be signaling feed intake and regulating insulin activity to support recovery from weight and muscle loss. The time it takes from when a mother’s litter is weaned and she is able to be rebred is referred to as weaning-to-estrus interval. In the current study, first-time mothers with increased plasma lactate levels at weaning had a longer weaning-to-estrus interval. Supplementing first-time mothers with creatine during lactation and shortly thereafter may assist with milk production and muscle loss recovery, decrease lactate levels, and improve time to rebreeding. Greater welfare and productivity of the sows and performance benefits to both the sow and her piglets could be realized.

2. Dietary development of gilts affects age at puberty. Proper development of female pigs (gilts) is critical for maximizing sow reproductive performance and longevity. Optimizing growth rates and body composition of gilts is vital to successful gilt development. For example, gilts that are too fat or too lean at puberty have reduced fertility and lifetime productivity, while faster growing gilts reach puberty sooner than slower growing gilts. To improve growth rate and reduce age at puberty while optimizing body condition, ARS scientists at Clay Center, Nebraska, used diets that differed in nutrient composition to produce high, medium, and low growth rates in gilts. Although gilts had different growth rates, composition of body growth as defined by the fat to lean ratio was not different among animals on different diets. For producers, this study demonstrates that diets can be developed to improve growth of gilts and reduce age at puberty, while optimizing body composition, resulting in greater longevity and lifetime productivity.

3. Colostrum deficiency in piglets affects the response of the uterus to pregnancy in adulthood. The first milk that a pig consumes from its mother is called colostrum. Colostrum is known to contain many hormones and morphoregulatory factors that impact development of multiple tissues and organ systems, which has important implications for the development of piglets to maturity. Previous research from ARS showed if female piglets do not get adequate colostrum at birth, their reproductive capacity is diminished. Therefore, ARS scientists at Clay Center, Nebraska, in collaboration with scientists from Auburn and Rutgers Universities, measured the amount of colostrum that gilt piglets consumed at birth and then followed these pigs to adulthood where they studied uterine performance during pregnancy. Scientists discovered over 1,100 genes in the pregnant uterus that were expressed differently in gilts that had consumed adequate amounts of colostrum as piglets compared with those that did not. Most of these genes were involved in immunity and in receptivity of the uterus to the fetus. Changes in gene expression in the uterus were likely controlled by an epigenetic mechanism called microRNA, which is programed by consumption of colostrum in the first day of life. This research strongly indicates that colostrum deficiency on the first day alters the development of the uterus with lasting effects on uterine responses to pregnancy, leading to impaired fertility and litter size. This research provides vital information that helps producers understand how managing colostrum consumption of gilts impacts long-term reproductive potential, which has important impacts on the productivity and profitability of pork production.

4. Gonadotropin-releasing hormone 2 receptor (GnRHR-2) controls testicular function in boars. Over 80% of sows in commercial pork production are artificially inseminated and thus semen production and fertility of male pigs (boars) has a major impact on the efficiency of swine production. Understanding testicular function of boars, therefore, is critically important in order to develop methods to improve reproductive efficiency in swine. ARS scientists at Clay Center, Nebraska, in collaboration with scientists at the University of Nebraska, blocked the gonadotropin-releasing hormone 2 receptor (GnRHR-2) in order to understand how testicular function in boars is controlled. In this study the expression of GnRHR-2 in the testes of pigs was reduced by almost 70%, resulting in pigs developing smaller testes and producing less testosterone, a hormone that is vital to sexual behavior and sperm production in males. This research is the first to demonstrate that GnRHR-2 is an important regulator of testicular function in boars and will lead to new methods to enhance fertility in swine.

5. Energy balance affects secretion of reproductive hormones controlling puberty in pigs. Female pigs (gilts) are typically selected for the breeding herd at an early age before they reach puberty. There is substantial variation in the age at which gilts reach puberty and many gilts fail to reach puberty on time, which results in being culled from the herd without producing pigs. Growth rates are known to affect age at puberty in pigs, consequently, ARS scientists at Clay Center, Nebraska, studied how short-term changes in energy balance affect physiological mechanisms that control attainment of puberty. Scientists discovered that release of a reproductive hormone called luteinizing hormone (LH) can be affected by subtle differences in energy balance. They also discovered that expression of several genes that control secretion of reproductive hormones also change with energy balance. This research provides important insights that can now be used to develop methods to improve pubertal development of gilts, resulting in improved sow reproductive performance for pork producers.

Review Publications
Rempel, L.A., Vallet, J.L., Nonneman, D.J. 2018. Characterization of plasma metabolites at late gestation and lactation in early parity sows on production and post-weaning reproductive performance. Journal of Animal Science. 96(2):521-531. https://doi.org/10.1093/jas/skx066.
Rempel, L.A., Rohrer, G.A., Nonneman, D.J. 2017. Genomics and metabolomics of post-weaning return to estrus. Molecular Reproduction and Development. 84(9):987-993. https://doi.org/10.1002/mrd.22820.
Laughlin, T.D., Miles, J.R., Wright-Johnson, E.C., Rempel, L.A., Lents, C.A., Pannier, A.K. 2017. Development of pre-implantation porcine blastocysts cultured within alginate hydrogel systems either supplemented with secreted phosphoprotein 1 or conjugated with Arg-Gly-Asp Peptide. Reproduction, Fertility and Development. 29(12):2345-2356. https://doi.org/10.1071/RD16366.
Rempel, L.A., Krautkramer, M.M., Loether, T.M., Parrish, J.J., Miles, J.R. 2018. Season of collection and sperm head shape impacts expression of CARHSP and FTL from motile-rich boar sperm. AGRI GENE. 7:1-6. https://doi.org/10.1016/j.aggene.2017.10.002.
Rempel, L.A., Miles, J.R., Parrish, J. 2016. Evaluation of contributions to seasonal reproductive inefficiency; NPB #14-052. National Pork Board. Available: http://research.pork.org/FileLibrary/ResearchDocuments/14-052-REMPEL-final%20rpt.pdf.
Calderon-Diaz, J.A., Vallet, J.L., Boyd, R.D., Lents, C.A., Prince, T.J., DeDecker, A.E., Phillips, C.E., Foxcroft, G., Stalder, K.J. 2017. Effect of feeding three lysine to energy diets on growth, body composition and age at puberty in replacement gilts. Animal Reproduction Science. 184:1-10. https://doi.org/10.1016/j.anireprosci.2017.06.007.
Caperna, T.J., Shannon, A.E., Stoll, M.J., Kahl, S., Blomberg, L., Vallet, J.L., Ramsay, T.G. 2017. A sandwich ELISA for porcine alpha-1acid glycoprotein (pAGP, ORM-1) and further demonstration of its use to evaluate growth potential in newborn pigs. Domestic Animal Endocrinology. 60:75-82. doi: 10.1016/j.domaniend.2017.04.001.
Vallet, J.L., Miles, J.R., Freking, B.A., Meyer, S. 2017. Glucosamine supplementation during late gestation alters placental development and increases litter size. JOURNAL OF ANIMAL SCIENCE AND BIOTECHNOLOGY. 8:68. https://doi.org/10.1186/s40104-017-0198-9.
Miles, J.R., Laughlin, T.D., Sargus-Patino, C.N., Pannier, A.K. 2017. In vitro porcine blastocyst development in three-dimentional alginate hydrogels. Molecular Reproduction and Development. 84(9):775-787. https://doi.org/10.1002/mrd.22814.
Prezotto, L.D., Thorson, J.F., Borowicz, P.P., Peine, J.L., Bedenbaugh, M., Hileman, S.M., Lents, C.A., Caton, J.S., Swanson, K.C. 2018. Influences of maternal nutrient restriction and arginine supplementation on visceral metabolism and hypothalamic circuitry of offspring. Domestic Animal Endocrinology. 65:71-79. https://doi.org/10.1016/j.domaniend.2018.06.001.
Thorson, J.F., Prezotto, L.D., Adams, H., Petersen, S.L., Clapper, J.A., Wright, E.C., Oliver, W.T., Freking, B.A., Foote, A.P., Berry, E.D., Nonneman, D.J., Lents, C.A. 2018. Energy balance affects pulsatile secretion of luteinizing hormone from the adenohypophesis and expression of neurokinin B in the hypothalamus of ovariectomized gilts. Biology of Reproduction. 99(2):433-445. https://doi.org/10.1093/biolre/ioy069.