PHYSIOLOGICAL ROLES OF PROSTAGLANDINS AND INTERFERON TAU IN CONCEPTUS DEVELOPMENT AND ENDOMETRIAL FUNCTION

• Sponsoring Institution: National Institute of Food and Agriculture
• Project Status: COMPLETE
• Funding Source: AFRI COMPETITIVE GRANT
• Reporting Frequency: Annual
• Accession No.: 0226771
• Grant No.: 2009-65203-31188
• Proposal No.: 2011-04464
• Project Start Date: May 1, 2011
• Project End Date: Jul 31, 2013
• Grant Year: 2012
• Program Code: [92320]- Animal Reproduction

Recipient Organization
WASHINGTON STATE UNIVERSITY
240 FRENCH ADMINISTRATION BLDG
PULLMAN,WA 99164-0001

Performing Department
Animal Science

Non Technical Summary
The proposed research supports objectives of the Animal Reproduction Program to increase our knowledge base for reproductive biology of agriculturally important animals with the goal of reducing infertility and improving fertility in breeding populations of agriculturally important animals. This proposal specifically addresses the FY2009 priority area of embryonic and fetal development, including the interaction between the conceptus and its uterine environment. The greatest limitation to reproductive efficiency across mammalian species is embryonic mortality, estimated to be 25% to 45% or greater in ruminants. Most early pregnancy losses are characterized by asynchrony between the conceptus and uterus, resulting in defective recognition and establishment of pregnancy. Although the cellular events that define the various stages of conceptus elongation and implantation have been described in ruminants, the underlying physiological pathways that are crucial to this process, and how they interact, are not clearly understood. Our central hypothesis is that peri-implantation conceptus growth and development in ruminants is modulated by secretions of the endometrium that are regulated by factors produced by the ovary (progesterone), the conceptus (interferon tau and prostaglandins), and perhaps endometrium itself (prostaglandins). The proposed research focuses specifically on the physiological roles of conceptus-derived factors (prostaglandins and interferon tau) on endometrial function and conceptus development during the peri-implantation period of early pregnancy using sheep as a model. Discovery of physiological pathways mediating conceptus-uterine interactions provide fundamental knowledge that is important for the development of strategies to reduce infertility and improve fertility, thereby impacting the profitability of animal production enterprises.

Animal Health Component

20%

Research Effort Categories

Basic

60%

Applied

20%

Developmental

20%

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
301	3610	1020	50%
301	3610	1050	25%
301	3610	1030	25%

Knowledge Area
301 - Reproductive Performance of Animals;

Subject Of Investigation
3610 - Sheep, live animal;

Field Of Science
1030 - Cellular biology; 1020 - Physiology; 1050 - Developmental biology;

Keywords

sheep

uterus

reproduction

prostaglandin

interferon

embryo

Goals / Objectives
Long-term research goals are to: (1) identify and determine the function of physiological pathways regulating uterine-conceptus (embryo/fetus and associated extraembryonic membranes) interactions that are crucial for conceptus survival and development; and (2) use this fundamental knowledge to improve reproductive efficiency and profitability of animal production enterprises. Although the cellular events that define the various stages of conceptus development and implantation have been described, the physiological pathways that underlie this process in the uterus and conceptus, and how they interact, are not clearly understood. The central hypothesis is that peri-implantation conceptus growth and development in ruminants is modulated by secretions of the uterine endometrium that are regulated by factors produced by the ovary (progesterone or P4), conceptus (interferon tau or IFNT and prostaglandins or PGs), and perhaps endometrium itself (PGs). The central hypothesis will be addressed by three objectives using sheep as a model ruminant to determine the physiological role of: (1) conceptus-derived prostaglandins on endometrial function and conceptus development; (2) interactions between prostaglandins, IFNT and progesterone on endometrial function and conceptus development; and (3) prostaglandin receptors in conceptus development and trophoblast differentiation. Successful completion of these aims will fill a substantial gap in our knowledge of the physiological pathways governing interactions between the conceptus and its uterine environment during early pregnancy. Such fundamental knowledge is crucial for developing strategies to reduce infertility and improve fertility in breeding populations of agriculturally important animals.

Project Methods
The biological role of prostaglandins and interferon tau in endometrial function and conceptus development will be studied using in vivo physiological approaches. The experiments will be statistically analyzed and the results used to test the scientific hypotheses. The experimental results and findings will be published in scientific journals. The project will be evaluated by timely completion of the goals and objectives and the publication of findings in scientific journals. Measurable indicators of success will include presentation of abstracts at national and international meetings as well as scientific publications. In this way, the project will impact the larger scientific community and be transmitted to stakeholders.

Progress 05/01/11 to 07/31/13

Outputs
Target Audience: Target audiences include scientists in academia and the private sector as well as livestock producers. Efforts included presentations of seminars to deliver science-based knowledge to stakeholders and experiential learning opportunities. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Services performed include consulting and counseling of a graduate student assigned to the project. The graduate student, Piotr Dorniak, conducted research towards his doctorate, which was awarded in 2013. How have the results been disseminated to communities of interest? Publication of scientific findings and dissemination of research findings through presentations of project findings by the project director and graduate student. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Outcomes/impacts of the project included new fundamental and applied knowledgedisseminated throughpublications. In addition, one important outcome and impact of the project is the knowledge that prostaglandins are fundamentally important for establishment and maintenance of pregnancy in ruminants. For many years, one idea to improve pregnancy rates in cattlewas to treat the animals with an inhibitor of prostaglandin synthesis. The outcomes of the research clearly indicate that this idea is not correct and will lead to an increase in early pregnancy loss. Translation of this outcome should impact development of approaches to increase pregnancy rates in cattle, thereby impacting the sustainability and profitability of cattle production enterprises.

Publications

• Type: Conference Papers and Presentations Status: Published Year Published: 2013 Citation: Dorniak P, Bazer FW, Spencer TE. Physiology and Endocrinology Symposium: biological role of interferon tau in endometrial function and conceptus elongation. Journal of Animal Science 2013; 91:1627-1638
• Type: Journal Articles Status: Published Year Published: 2013 Citation: Dorniak P, Bazer FW, Wu G, Spencer TE. Conceptus-derived prostaglandins regulate endometrial function in sheep. Biology of Reproduction 2012; 87:9, 1-7.
• Type: Journal Articles Status: Published Year Published: 2013 Citation: Dorniak P, Welsh TH Jr, Bazer FW, Spencer TE. Cortisol and interferon tau regulation of endometrial function and conceptus development in female sheep. Endocrinology 2013; 154:931-941
• Type: Journal Articles Status: Published Year Published: 2013 Citation: Spencer TE, Forde N, Dorniak P, Hansen TR, Romero JJ, Lonergan P. Conceptus-derived prostaglandins regulate gene expression in the endometrium prior to pregnancy recognition in ruminants. Reproduction 2013; 146:377-387

Progress 05/01/11 to 04/30/12

Outputs
OUTPUTS: Activities performed during the reporting period included conducting and analyzing experiments, facilitating, and mentoring graduate students. One graduate student, Piotr Dorniak, presented experimental findings at the annual meeting of the Society for the Study of Reproduction in Portland, Oregon. In addition, the Project Director presented experimental findings at several invited talks including the University of Florida, Ludwig-Maximilians-Universitaet in Munich, Germany, Michigan State University, and at the Frontiers in Reproductive Sciences course at the Marine Biological Laboratory in Woods Hole, Massachusetts. Services performed include consulting and counseling of a graduate student assigned to the project. Products include an enhanced understanding the genetics of early pregnancy success in ruminants as well as graduate students trained in animal sciences. Outreach activities include publication of scientific findings and dissemination of research findings through presentation of project findings by the project director and graduate student. PARTICIPANTS: Project Director: Thomas E. Spencer, Washington State University; Graduate Student: Piotr Dorniak, Washington State University; Collaborators: Fuller W. Bazer, Thomas H. Welsh, Jr. and Guoyao Wu, Texas A&M University. Opportunities for training was primarily via Piotr Dorniak who is pursuing a Ph.D. and conducting experiments in the project. TARGET AUDIENCES: Target audiences include scientists and producers. Efforts included presentation of seminars to deliver science-based knowledge to stakeholders and experiential learning opportunities. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Outcomes/impacts of the project included new fundamental and applied knowledge included in publications. In addition, one important outcome and impact of the project is the knowledge that prostaglandins are fundamentally important for establishment and maintenance of pregnancy in ruminants. For many years, one idea to improve pregnancy rates in cattle has been to treat the animals with an inhibitor of prostaglandin synthesis. The outcomes of the research clearly indicate that this idea is not correct and will lead to an increase in early pregnancy loss. Translation of this outcome should impact development of approaches to increase pregnancy rates in cattle, thereby impacting the sustainability and profitability of cattle production enterprises.

Publications

• Dorniak P, Bazer FW, Spencer TE. Prostaglandins regulate conceptus elongation and mediate effects of interferon tau on the ovine uterine endometrium. Biology of Reproduction 2011; 84:1119-1127.
• Dorniak P, Bazer FW, Welsh Jr TH, Spencer TE. Endometrial HSD11B1 and cortisol regeneration in the ovine uterus: effects of pregnancy, interferon tau and prostaglandins. Biology of Reproduction 2012; 86:124.