Performing Department
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Non Technical Summary
This research project focuses on improving how often dairy cows successfully have calves, an important area for U.S. agriculture. Specifically, the project looks at why high-producing dairy cows (those that give a lot of milk) often have problems with pregnancies that do not go to term, particularly due to early death of embryos. This issue is costly for farmers and stems from complex biological problems not yet fully understood. Lactating cows experience changes in their body energy due to intense milk production right after giving birth. These changes can negatively affect the cows' reproductive organs and embryo health.The overall hypothesis of this research is that the balance of oxygen and sugar levels, controlled by the environment inside the uterus, plays a crucial role in the early development of embryos and their stem cells, ultimately influencing whether they can successfully attach to the uterus and continue developing.The study has two main goals:1. Understanding Embryo Needs: By measuring sugar and oxygen levels in the uterus, the research aims to find out what embryos need to develop healthily and if these needs are different in cows that are lactating compared to younger heifers. This could lead to better understanding of how to support embryo growth during early stages.2. Studying Gene Activity: The project also plans to examine how sugar and oxygen levels influence embryo development at the genetic level. This involves looking at how genes in the embryos are turned on or off by these conditions and could tell us more about why some embryos fail to develop properly.The findings from this research could lead to better ways to help cows have successful pregnancies and improve methods for creating embryos in the lab (in vitro). This would not only help reduce financial losses for farmers but also enhance the productivity and sustainability of dairy farming.
Animal Health Component
100%
Research Effort Categories
Basic
100%
Applied
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Developmental
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Goals / Objectives
This research addresses reproduction efficiency in dairy cattle by investigating embryonic development, a research focus in the USDA animal reproduction priority area. In contrast to heifers, high-producing dairy cows suffer increased pregnancy failures due to early embryo death. This is strongly associated with compromised embryo development and/or failed uterine attachment (implantation). Although the economic loss is quite significant for farms, there are no known fixes to this problem as underlying mechanisms remain largely unknown. Metabolic challenges of lactation such as negative energy balance are known to occur in the postpartum background in cows, but not in heifers during the breeding period. Yet, concomitant influence of such systemic energy partitioning on uterine function remains uncharacterized. In this project, we investigate the uterine environment to understand the favorable vs challenging metabolic settings and assess impact on developing embryos.Aim 1: By measuring in vivo uterine glucose and oxygen levels, we will uncover basic embryonic needs, and possible differences in lactating cows vs heifers. Concurrently, we will identify the optimal oxygen-calibrated glucose demands for rapid proliferation of embryonic trophoblasts (placental precursor cells) representative of growth during preimplantation embryo development.Aim 2: By mapping the transcriptional regulatory landscape of embryo growth and metabolism, we will define the influence of glucose and oxygen on the developmental regulation of trophoblasts (capturing both immediate embryonic and future possible placental problems).This research will advance the efficiency of US agriculture by uncovering mechanisms towards recovering high fertility in modern dairy cows, and providing information for biomimicry promoting superior in vitro embryo production systems.
Project Methods
The research project aims to enhance understanding of the conditions that support the early stages of embryo development in dairy cows. It is structured around two main aims, each with distinct methodologies:Aim 1: Determining Uterine Luminal Oxygen and Glucose LevelsMethods: This aim involves directly measuring in vivo levels of oxygen and aspects of glucose homeostasis within the uterus of both cycling and early pregnant dairy cows and heifers. We will use a fiber-optic oxygen sensing probe with built in temperature compensation to directly read out dissolved oxygen availability for the embryo within the uterine fluid at different stages of the preimplantation period. This approach of in vivo measurements will provide a clear understanding of the metabolic impact in this microenvironment and optimal conditions needed for preimplantation embryo development.Aim 2: Defining the Influence of Oxygen and Glucose on Trophoblast Transcriptional ProgramsMethods: The team will employ Precision Run-On sequencing (PRO-seq) to analyze gene loci that are transcriptionally active and are poised for stimulus-dependent activation in trophoblast stem cells. This technique will specifically assess how these loci are regulated under conditions of low oxygen or physiological hypoxia and varying glucose levels. The approach combines advanced sequencing techniques with novel bioinformatics tools developed at Cornell University.Together, these methods will provide critical insights into the environmental and genetic factors influencing embryo development and pave the way for technological advances in embryo production practices.