Source: PENNATEK, LLC submitted to
SYNCHRONIZED OVULATION WITH A NOVEL TRIPTORELIN GEL DELIVERY SYSTEM FOR USE OF FIXED TIME AI IN MATRIX TREATED GILTS.
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
0210120
Grant No.
2007-33610-18091
Cumulative Award Amt.
(N/A)
Proposal No.
2007-00023
Multistate No.
(N/A)
Project Start Date
Jun 15, 2007
Project End Date
Feb 14, 2008
Grant Year
2007
Program Code
[8.3]- (N/A)
Recipient Organization
PENNATEK, LLC
5 RADNOR CORPORATE CENTER, SUIT 520
RADNOR,PA 19087
Performing Department
(N/A)
Non Technical Summary
The success of the US pork industry depends upon high fertility in the breeding herd. Unfortunately, sow culling rates of 50% force producers to maintain large pools of replacement gilts. Until the progestagen, Matrix (altrenogest), was approved by the FDA there was no product available to synchronize the estrous cycle of females in the gilt pool. Greater than 85% of gilts display estrus within 4 to 9 days after withdrawal of Matrix. Unfortunately, the 4-5 day spread in estrus synchrony precludes use of fixed-time or single service AI. Therefore, an additional treatment to more precisely control ovulation is needed so that all gilts in a group may be inseminated without regard to estrus. The overall objective of this research is to develop a method to control time of ovulation in Matrix treated gilts. The new OvuGel treatment has successfully synchronized ovulation in weaned sows through delivery of a GnRH agonist gel by an intravaginal delivery system. These studies will determine the minimum effective dose and most effective time to administer OvuGel after withdrawal of Matrix in gilts. The direct economic benefits of this system include: decreased labor, feed and facilities costs, decreased number of boars, decreased days a female is not pregnant or not lactating and increased litter size. Indirect effects will also decrease consumption of natural resources and the environmental impact associated with swine production.
Animal Health Component
100%
Research Effort Categories
Basic
(N/A)
Applied
100%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
30135101020100%
Knowledge Area
301 - Reproductive Performance of Animals;

Subject Of Investigation
3510 - Swine, live animal;

Field Of Science
1020 - Physiology;
Goals / Objectives
The overall objective is to determine whether a gonadotropin releasing hormone agonist (GnRHa) can be used to effectively synchronize ovulation in Matrix-treated gilts. Pennatek LLC is currently developing a vaginally delivered GnRHa gel product, OvuGel, to synchronize ovulation in weaned-sows and will extend its research to Matrix-treated gilts under this grant. The first objective is to determine the optimal time of OvuGel treatment after withdrawal of Matrix on synchrony of ovulation in postpubertal gilts. This study will be performed in four replicates of 20 gilts each at the JBS United, Inc. research farms in Sheridan, Indiana during May-July 2007. Each gilt will be individually fed Matrix as a top dress for 14 days at the recommended rate of 15 mg/gilt/day. OvuGel without GnRHa (Control), or OvuGel containing a maximum dose of GnRHa will be administered intravaginally at 96 hours (OG96), 120 hours (OG120), or 144 hours (OG144) following Matrix withdrawal. The gilts will then be examined for ovarian follicle size and time of ovulation using transrectal real-time ultrasound at 8-hour intervals between 96 hours until 200 hours after last Matrix feeding. Data collection will include average follicle size at each ultrasound examination, interval from Matrix to onset of estrus, duration of estrus, interval from Matrix to ovulation, and the percentage of gilts ovulating at 8-hour intervals between 96 and 168 hours following Matrix withdrawal. The second objective is to determine the effect of dose of OvuGel after withdrawal of Matrix on the timing of ovulation and the timing and magnitude of the periovulatory LH surge. This study will be performed in four replicates at the JBS United, Inc. research farms in Sheridan, Indiana during August thru December 2007. Each gilt will be individually fed Matrix as a top dress for 14 days followed by 2 mL of OvuGel without GnRHa (Control), or 2 mL of OvuGel containing increasing doses of GnRHa at a single time point established by the results from the study described above. Again, the gilts will be examined for ovarian follicle size and time of ovulation using transrectal real-time ultrasound at the time of OvuGel treatments and at 8-hour intervals for 56 hours. Data collection will include average follicle size at each ultrasound examination, the interval from Matrix withdrawal until estrus, duration of estrus, interval from withdrawal until ovulation, and the percentage of gilts ovulated at selected intervals following withdrawal of Matrix (96 h, 104 h, 112 h etc.). The hormone data will include the magnitude of the LH surge, the area under the curve for the LH surge, and the interval from last feeding of Matrix until the LH peak. Together these studies will demonstrate whether a vaginally applied GnRHa can be used to effectively synchronize ovulation in Matrix-treated gilts and will determine the optimal dose and time of treatment for the GnRHa administration.
Project Methods
The first objective will be to determine the effect of time of OvuGel treatment after withdrawal of Matrix on synchrony of ovulation in postpubertal gilts. This study will be performed in four replicates of 20 gilts each at the JBS United, Inc. research farms in Sheridan, Indiana. Maternal line PIC C-22 replacement gilts, which have expressed at least one estrus will be weighed and moved to gestation stalls. Each gilt will be individually fed Matrix as a top dress for 14 days at the recommended rate of 15 mg/gilt/day. Within each replicate, 5 gilts each will be assigned by weight and age to receive 2 mL of OvuGel without triptorelin acetate (Control), or to receive OvuGel containing 200 mcg of triptorelin acetate at 96 hours (OG96), 120 hours (OG120), or 144 hours (OG144) following last Matrix feeding. OvuGel will be administered intravaginally using a multi-dose applicator. Gilts will be examined for ovarian follicle size and time of ovulation using transrectal real-time ultrasound at 8-hour intervals from 96 hours until 200 hours following last Matrix feeding. An Aloka 500 ultrasound machine is used for this purpose, with a 7.5 MHz linear array transducer attached to a fixed-angle PVC stabilizing rod to facilitate insertion into the rectum. The transducer and PVC rod are coated with a gynecological lubricant and gently inserted into the rectum until the ovaries can be visualized, one at a time. The second objective will be to determine the effect of dose of OvuGel after withdrawal of Matrix on the timing of ovulation and the timing and magnitude of the periovulatory LH surge. This study will be performed in four replicates of 20 gilts each at the JBS United, Inc. research farms in Sheridan, Indiana. Maternal line PIC C-22 replacement gilts, which have expressed at least one estrus will be weighed and moved to gestation stalls. Each gilt will be individually fed Matrix as a top dress for 14 days at the recommended rate of 15 mg/gilt/day. Within each replicate, 5 gilts each will be assigned by weight and age to receive 2 mL of OvuGel without GnRHa (Control), or 2 mL of OvuGel containing 3 different doses of GnRHa at a single time point established by the results from study described above (96-200 hours following Matrix withdrawal). Gilts will be examined for ovarian follicle size and time of ovulation using transrectal real-time ultrasound at the time of OvuGel treatments and at 8-hour intervals for 56 hours. A subpopulation of gilts (n=6/treatment) will receive a non-surgical catheter in the jugular vein. Ten mL blood samples will be collected into EDTA treated tubes every 15 minutes for one hour prior to treatment, immediately following treatment (0) and at 0.5, 1, 2, 4, 6, 12, 18, 24, 36, 42, and 48 hours after treatment. Blood samples will be maintained at 4 degrees Celsius until centrifuged at 800 x g for 15 min within 12 h of collection. The plasma will be aliquotted into tubes and stored frozen until assayed for LH using reagents from the National Hormone and Peptide Program (Harbor-UCLA Medical Center, Torrence, CA).

Progress 06/15/07 to 02/14/08

Outputs
OUTPUTS: Unfortunately, sow culling rates of 50% in the US pork industry force producers to maintain large pools of replacement gilts. A FDA approved orally active progestagen, MATRIX (altrenogest), effectively synchronizes the estrous cycle of females in the gilt pool. Greater than 85% of gilts display estrus within 4 to 9 days after withdrawal of MATRIX. The 4-5 day spread in estrus synchrony precludes use of fixed time or single service AI. Therefore, an additional treatment to more precisely control ovulation is needed so that all gilts in a group may be inseminated without regard to estrus. Pennatek LLC has developed the ovulation induction product, OvuGel, a slow release formulation of the gonadotropin releasing hormone (GnRH) analog, triptorelin acetate, which is delivered intravaginally. This project was designed to understand the variation in onset of ovulation after the last feeding of MATRIX to post pubertal gilts, and to develop an OvuGel treatment protocol to precisely synchronize ovulation in MATRIX-treated gilts. The objectives were: (A) to determine the effect of time of OvuGel treatment after last feeding of MATRIX on synchrony of ovulation and (B) to determine the effect of dose of OvuGel after last feeding of MATRIX on timing of ovulation and timing and magnitude of the periovulatory LH surge. In Objective A, gilts were individually fed MATRIX for 14 days. Gilts then received OvuGel without triptorelin acetate or OvuGel containing 200 mcg of triptorelin at 96, 120, or 144 hours after last MATRIX feeding. Results indicated that an interval between 96 and 120 hours after last feeding of MATRIX is the optimum time for OvuGel treatment. In Objective B, gilts were individually fed MATRIX as in Objective A. Gilts then received OvuGel without triptorelin acetate or OvuGel containing 100 mcg, 200 mcg or 400 mcg of triptorelin at 120 hours after last feeding of MATRIX. Blood samples were collected from a subpopulation of gilts in each treatment group via a jugular vein catheter to characterize LH secretion. Collectively, there was a beneficial effect of the OvuGel treatments on ovulation synchrony. Results demonstrated that OvuGel doses between 100-400 mcg triptorelin, administered at 120 hours after last feeding of MATRIX advanced ovulation compared to placebo at 160 to 176 hours after last feeding of MATRIX. Therefore, this dose range of OvuGel is effective for synchronizing ovulation after estrous cycle synchronization with MATRIX in gilts. The serum LH data are consistent with these conclusions. Based on our previous investigations in gilts and postpartum sows and results from these studies it is feasible to develop a standard ovulation synchronization protocol, which is equally effective in both sows after weaning and gilts after synchronization of estrus with MATRIX treatment. PARTICIPANTS: Dr. Stephen Webel is the Principle Investigator of this proposed research project. Dr. Webel is Director of Reproduction Research and Development at JBS United, Inc., which is one of the founding partners of the joint venture company, Pennatek LLC. He has over 40 of years of experience in research, teaching, consulting and administration in swine reproductive physiology. Dr. Webel is also an Officer at Pennatek LLC and serves as the company's Vice President of Research. Dr. Robert Kraeling, L&R Research Associates, Inc., is a co-principle investigator/collaborator on this research project. He has over 35 years of experience in research, teaching and administration in swine reproductive physiology. Dr. Kraeling retired from a 34 year career with ARS, USDA in 2004. Dr. Robert Knox is Associate Professor of Animal Science, University of Illinois is a co-principle investigator/collaborator on this research project. He has over 15 years of experience in research, teaching and extension in swine reproduction, including specific expertise in transrectal ultrasound techniques used to monitor ovulation in swine. Mark Swanson, Vice President of Product Development at Pennatek, served a supporting role in administration and project management. He has over 21 years of experience in research and administration in the pharmaceutical and biotechnology industries. Chris Anderson of Pennatek provided administrative support. Dr. Clay Lents, Assistant Professor, Department of Animal and Dairy Science conducted the luteinizing hormone assays. Dr. Lents joined the University of Georgia faculty three years ago. His research program focuses on investigating neuroendocrine control of gonadotropin secretion in ruminants and swine. This project provided training opportunities to graduate students; primarily, Jessica Taibl and Shawn Breen, and others under the direction of Dr. Knox. These graduate students as well as undergraduate students assisted in the experimental design, data entry and analysis, and report preparation. They also assisted with execution of ultrasonography, blood sampling and processing, and hormone assays. Farm managers and research technicians employed at JBS United's Sheridan and Burton Russell Research Farms provided animal handling support for the animals used in these studies, as well as the care and well being of all animals involved in these studies. TARGET AUDIENCES: There are approximately 67,000 pig producers in the U.S. Of these, 25 producers maintain more than 25,000 sows/gilts and represent approximately 40% of production. These largest producers will be our primary target. Our secondary target will be the 130 producers with 2,500 - 25,000 sows/gilts who account for approximately 20% of production. We will also market to the 2,400 producers with 250 - 2,500 sows/gilts who account for 28% of production. The key players involved in the purchase decision, in order of likely influence, will include swine veterinarians, pig production operators, and purchasing personnel. Swine veterinarians may be employed by the producer or serve as independent consultants. We will also target pork producers in the U.S., Canada and the EU. When the results from this project are published, other scientists in academia and the animal pharmaceutical industry will use this information as a basis for further research and university extension personnel will use this information to make swine producers aware of this new technology.

Impacts
Application of this method to precisely control ovulation in both weaned sows and Matrix treated gilts will revolutionize how pigs are mated. Synchronized ovulation facilitates the use of fixed-time, single service AI, while eliminating the labor previously required for detection of estrus. This synchronized estrus and ovulation system allows for insemination of all females in a particular group at the same time and at the peak time of fertility. Adoption of this system will result in increased genetic progress because sires of higher genetic merit will be used across the entire breeding herd. The labor costs associated with operation of the replacement gilt pool will be reduced due to elimination of estrus detection during the combined estrous cycle synchronization and ovulation synchronization procedures. This needle free administration system will reduce the risk of needle shafts in pork carcasses and the need to trim pork cuts due to the presence of needle injection sites. Preliminary market research has demonstrated a very strong interest among swine producers for this technology. Because there are currently no products or technology available to producers for inducing ovulation to permit timed insemination, producer interest in this concept has been very high. Cost of feed, labor, manure handling, utilities, transportation expenses, insurance, taxes, facility and equipment maintenance, and animal health expenses, such as vaccines, parasite control, antibiotics and veterinary charges continue to increase, while the price received by pork producers has failed to increase at the same rate resulting in shrinking profit margins. Thus, pork producers are under pressure to do everything possible to increase efficiency of production. Demand for OvuGel is based on the fact that reproductive efficiency is a major factor in determining the overall efficiency of pork production. The key players involved in the purchase decision, in order of likely influence, will include swine veterinarians, pig production operators, and purchasing personnel. Swine veterinarians may be employed by the producer or serve as independent consultants. In smaller companies, those with less than 2,500 sows, the owner of the company is the primary decision maker with the other key players serving as influencers. Currently there are no products on the market, nor are we aware of any products in development, that facilitate a fixed-time insemination of postpartum sows or MATRIX-treated gilts. We expect to successfully compete with competitive entrants by being first to market, providing a product with proven efficacy in a non-injectable form.

Publications

  • No publications reported this period