Progress 04/01/10 to 03/31/15
Outputs
Target Audience: Veterinarians, animal scientists, horse breeders, human andrologists Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided? Numerous opportunities to master clinical techniques, such as semen collection and evaluation, taking testicular biopsies, frequent blood draws, ultrasound evaluations of the scrotum, etc. How have the results been disseminated to communities of interest? Scientific and clinical presentations, review articles What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
IMPACT There are continues efforts to fight animal overpopulation.Whereas the main target of contraception in humans and animals is a female, there is a growing interest in developing a "pill" or "shot" for males as well. The recent studies on rodents suggested that an indenopyridine derivative l-CDB-4022 (current name - RTI-4587-073(l )) could be a good candidate of a male contraceptive. Therefore, the first goal of this research was to determine the effects of administration of a single dose of RTI-4587-073(l) on various parameters of stallion semen, sexual behavior, testicular histological structure and reproductive hormones. In addition, we investigated whether this treatment can be used to create a model of medically induced, reversible testicular degeneration in stallions, which is a major cause of male infertility in horses. In order to accomplish these two goals, two replicates of a similar study were conducted. In the first replicate, a single dose of the compound was given to three Miniature horse stallions, while other three stallions received placebo only. Semen was collected and evaluated from all stallions twice a week for three baseline weeks and 13 post-treatment weeks. Small samples of semen were frozen sent off for sperm chromatin structure (sperm DNA structure) analysis to the College of Veterinary Medicine, Texas A&M University. Sexual behavior was video-recorded and analyzed by a non-biased specialist in sexual behavior (Dr. Sue McDonnell, University of Pennsylvania). Testicular dimensions were measured using ultrasonography, and blood samples were drawn for endocrine evaluation once before treatment, and once a week during the post-treatment period. Endocrine analysis was performed in Roser lab, University of California Davis. The results of this study clearly showed that the single administration of (RTI-4587-073(l) (former l-CDB-4022) causes severe changes in stallion semen (very low sperm number, low motility, damages DNA structure, and increases concentrations of follicle stimulating hormone (FSH) in treated stallions. These effects were fully reversible within approximately 71 days. Libido and copulatory behavior remained unchanged throughout the entire experiment. The second replicate of the study focused on acute endocrine effects of the compound as well as histological changes in testicular parenchyma induced by the compound. After several months of rest, the groups of the Miniature stallions were switched and the previously treated animals served as controls and the other three stallions (previously controls) received a single dose of RTI-4587-073(l). Semen was collected and evaluated as previously. Frequent samples of blood were taken for endocrine analysis. Ultrasound exams were performed to monitor the dimensions of the stallions' testes. Testicular biopsies were obtained before treatment, one day after treatment, and every other week after treatment. All stallions were castrated six weeks after treatment and testicular tissues were taken from all specimens. All samples of testicular tissue were sent off for analysis to an unbiased specialist in testicular histomorphology (Dr. Rex Hess, University of Illinois. This analysis showed severe effects of the compound on the cellular architecture of treated stallions consistent with severe testicular degeneration. These changes were still present in the testicular samples taken from treated stallions after castration, six weeks post treatment. The combined results of both replicates of our study clearly showed that a single administration of RTI-4587-073(l) causes significant but reversible suppression of testicular function in stallions without affecting sexual behavior. These characteristics make the compound a good candidate for a male contraceptive. Furthermore, the compound causes severe changes in testicular histomorphology that are consistent with testicular degeneration. Based on our results, we can conclude that a single administration of RTI-4587-073(l) to stallions creates a great model of testicular degeneration. Objectives: Establish effects of a treatment with l-CDB-4022 on semen parameters in stallions Three Miniature horse stallions received a single dose of 12.5 mg/kg RTI-4587-073(l) per os (Group TREATED), while three other Miniature horse stallions received placebo only (Group CONTROL). Semen was collected and evaluated from all stallions twice a week for three baseline weeks and 13 post-treatment weeks. Significant effects of RTI-4587-073(l) or vehicle on semen parameters, endocrine values, and behavioral endpoints within each group, were determined using one-way ANOVA tests with comparisons to the last week before treatment (BASELINE). Differences between groups were determined using linear models ANOVA with two factors, and with interactions (groups and collection days), followed by Tukey's test. The single administration of RTI-4587-073(l) caused severe oligoasthenozoospermia (low sperm number and low motility) and shedding large numbers of immature germ cells in semen. These effects were fully reversible within approximately 71 d. Establish effects of a treatment with RTI-4587-073(l) (former l-CDB-4022) on sexual behavior in stallions Sexual behavior was recorded and analyzed, using objective methods. There were no differences between groups or within any of the groups in the behavioral endpoints, including the overall efficiency of semen collection between both groups, as expressed by individual ranks. All stallions showed adequate sexual interest and normal copulatory behavior throughout the study. The key outcome of these two parts of the study (Objective #1 and #2) is that a single administration of RTI-4587-073(l) severely but transiently suppresses testicular function without affecting sexual behavior. This makes this compound a great candidate for a male contraceptive. Establish effects of a treatment with l-CDB-4022 on concentrations of reproductive hormones in stallion During the second replicate of the study, multiple blood samples were collected for endocrine analysis. Testicular biopsies were obtained before treatment, one day after treatment, and every other week after treatment. Samples of blood and testicular tissue were submitted for endocrine analysis. Testicular tissue was submitted for histological analysis as well. The effects of treatment with RTI-4587-073(l) concentration of hormones were analyzed with the two-factor ANOVA with interactions (treatment and hour), and means were compared using Tukey's test. Testosterone concentrations transiently decreased, followed by a slight increase in LH concentration after administration of RTI-4587-073(l). Testicular content of testosterone and estradiol 17-β was lower in treated stallions than in control stallions on Day 1 after treatment. There was a trend for testicular inhibin to be lower in treated stallions as well. Significant alterations of testicular tissue were observed in testicular biopsies obtained from treated stallions one day after treatment. These changes were still present in the testicular samples taken from treated stallions after castration. The results of this study demonstrated that RTI-4587-073(l) causes acute sloughing of immature germ cells from the seminiferous tubules, but sufficient numbers of germ cells are left to continue and restore spermatogenesis. RTI-4587-073(l) has significant but transient effects on Leydig cell function in stallions. The key outcome of this part of the study is a single administration of RTI-4587-073(l) does affect semen quality and sperm quantity, as well testicular histological structure, but does not drastically affect reproductive hormones. Therefore, endocrine tests may not be the best way to diagnose testicular degeneration in the horse. The investigated treatment with RTI-4587-073(l) seems to be a good way to induce a good model of testicular degeneration.
Publications
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2014
Citation:
Nollin M, Zambrano G, Pozor M. Effects of the contraceptive compound RTI-4587-073(l) on stallion behavior and semen. Havemeyer Workshop RM Kenney Symposium II - September 26-28, 2014
- Type:
Journal Articles
Status:
Published
Year Published:
2013
Citation:
Pozor MA, Macpherson ML, McDonnell SM, Nollin M, Roser JF, Love C, Runyon S, Thomas BF, Troedsson MH. Indenopyride derivative RTI-4587-073(l): A candidate for male contraception in stallions. Theriogenology 2013;80:1006 16.
- Type:
Journal Articles
Status:
Published
Year Published:
2014
Citation:
Pozor M, Nollin M, Roser J, Runyon S, Macpherson M, Kelleman A. Doppler indices of vascular impedance as indicator of testicular dysfunction in stallions. J Eq Vet Sci 2014; 34:38-39.
- Type:
Journal Articles
Status:
Published
Year Published:
2014
Citation:
Pozor MA, Zambrano G, Roser J, Hess R, Runyon S, Runcan E, Thomas BF, Dymock D, Macpherson M, Troedsson MH, Kelleman A. Acute and chronic effects of a contraceptive compound RTI-4587-073(l) on testicular histology and endocrine function in Miniature Horse stallion. Reprod Domest Anim 2014;49:392-402.
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Progress 10/01/13 to 09/30/14
Outputs
Target Audience: Veterinarians, animal scientists, horse breeders and human andrologists Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?
Nothing Reported
How have the results been disseminated to communities of interest? The results were published in three scientific journals and were presented at the International Symposium of Equine Reproduction in New Zealand. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
All samples from the second replicate of the study were evaluated and analyzed. All data of both replicates of the study were analyzed, manuscripts were prepared and submitted for publications, as well as for presentation at the international conference.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2014
Citation:
Pozor MA, Zambrano G, Roser J, Hess R, Runyon S, Runcan E, Thomas BF, Dymock D, Macpherson M, Troedsson MH, Kelleman A. Acute and chronic effects of a contraceptive compound RTI-4587-073(l) on testicular histology and endocrine function in Miniature Horse stallion. Reprod Domest Anim 2014;49:392-402.
- Type:
Journal Articles
Status:
Published
Year Published:
2014
Citation:
Runcan EE, Pozor MA, Zambrano GL, Benson S, Macpherson ML. Use of two conventional staining methods to assess the acrosomal status of stallion spermatozoa. Equine Vet J 2014; 46:503-506.
- Type:
Journal Articles
Status:
Published
Year Published:
2014
Citation:
Pozor M, Nollin M, Roser J, Runyon S, Macpherson M, Kelleman A. Doppler indices of vascular impedance as indicator of testicular dysfunction in stallions. J Eq Vet Sci 2014; 34:38-39.
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Progress 10/01/12 to 09/30/13
Outputs
Target Audience: Veterinarians, animal scientists, horse breeders, human andrologists Changes/Problems: We do not expect any problems. What opportunities for training and professional development has the project provided? This project provided very valuable opportunities for collaboration with the top scientists specializing in testicular histomorphology and in endocrinology. Furthermore, we performed numerous testicular biopsies on our research stallions and mastered this clinically useful technique. How have the results been disseminated to communities of interest? The results of this study were publishedin twojournals and presented at the Annual Convention of the American Association of Equine Practitioners. What do you plan to do during the next reporting period to accomplish the goals? The samples obtained during this reporting period will be analysed and submitted for publication.
Impacts
What was accomplished under these goals?
A second replicate of the study was performed In this reporting period of time. This replicate focused on the acute and chronic effects of a single administration of the contraceptive compound - RTI-4587-073(l), (former name - l-CDB-4022) on testicular histomorphology and endocrinology in stallions. Six Miniature stallions were used in this experiment. The treatment group (n = 3) received one oral dose of 12.5mg/kg of RTI-4587-073(l), the control group (n = 3) received placebo only. The stallions' baseline parameters (semen, testicular dimensions, endocrine values) were collected and recorded for five weeks before treatment and for five weeks after treatment. Semen was collected and evaluated weekly after treatment. Multiple blood samples were collected for endocrine analysis. Testicular biopsies were obtained before treatment, one day after treatment, and every other week after treatment. Ultrasound exams were performed to monitor the dimensions of the stallions' testes. All stallions were castrated six weeks after treatment. Sperm numbers, motility and percentage of morphologically normal sperm, decreased (P < 0.05), while the number of immature germ cells increased in ejaculates from treated animals (P < 0.05). Serum concentrations of inhibin and FSH did not change. Testosterone concentrations initially transiently decreased (P < 0.05) after administration of RTI-4587-073(l), and increased several days later (P <0.05). Testicular content of testosterone and estradiol 17-β was lower in treated stallions than in control stallions on Day 1 after treatment (P < 0.05). Severe disorganization of the seminiferous tubules, significant loss of immature germ cells, and complete depletion of elongated spermatids, were observed in testicular biopsies obtained from treated stallions one day, two weeks and four weeks after treatment. These changes were still present in the testicular samples taken from treated stallions after castration, six weeks post treatment. The results of this study confirmed that RTI-4587-073(l) has anti-spermatogenic effects in stallions. Furthermore, we concluded that this compound causes acute sloughing of immature germ cells from the seminiferous tubules. RTI-4587-073(l) has transient but significant effects on Leydig cell function in stallions.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2013
Citation:
Pozor MA, Macpherson ML, McDonnell SM, Nollin M, Roser JF, Love C, Runyon S, Thomas BF, Troedsson MH. Indenopyride derivative RTI-4587-073(l): A candidate for male contraception in stallions. Theriogenology 2013;80:1006 16.
- Type:
Journal Articles
Status:
Accepted
Year Published:
2013
Citation:
Runcan EE, Pozor MA, Zambrano GL, Benson S, Macpherson ML. Use of two conventional staining methods to assess the acrosomal status of stallion spermatozoa. Equine Vet J
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Progress 10/01/11 to 09/30/12
Outputs
Target Audience: The target audiences of this research are: veterinarians, animals scientists and horse breeders Changes/Problems: We do not anticipate any major problems What opportunities for training and professional development has the project provided? This project provided material to train student workers and veterinary students participating in this study, in various techniques used in equine reproduction, such as: stallion handling, administration of medications, blood draws, semen collections and evaluations. How have the results been disseminated to communities of interest? The selected results of these study were submitted for presentation at the Annual Convention of the American Association of Equine Practitioners. What do you plan to do during the next reporting period to accomplish the goals? The second part of the study will be performed. This replicate will focus mainly on the acute and chronic effect of a single administration of histological changes and on the endocrine effects of a single administration of RTI-4587-073(l) on testicular histomorphology and on endocrinology.
Impacts
What was accomplished under these goals?
During the reported period of time the first replicate of the study was performed. Three Miniature horse stallions received a single dose of 12.5 mg/kg RTI-4587-073(l) orally (group "treated"), whereas three other Miniature horse stallions received placebo only (group "control"). Semen was collected and evaluated from all stallions twice a week for three baseline weeks and 13 post-treatment weeks. Sexual behavior was video-recorded and analyzed. Testicular dimensions were measured using ultrasonography, and blood samples were drawn for endocrine evaluation once before treatment and once a week during the post-treatment period. The single administration of RTI-4587-073(l) caused severe oligoasthenozoospermia (low sperm number and low motility), shedding large numbers of immature germ cells in semen, and increased concentrations of FSH in treated stallions. These effects were fully reversible within approximately 71 d. Libido and copulatory behavior remained unchanged throughout the entire experiment. We concluded that RTI-4587-073(l) is a promising candidate for male contraceptive in domestic stallions and is ideal to create a model of testicular degeneration. Further research should be performed to test applications of this compound in fertility control in wildlife and in humans.
Publications
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2012
Citation:
Proceedings of the Annual Convention of the American Association of Equine Practitioners, Anaheim, 2012
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Progress 10/01/10 to 09/30/11
Outputs
OUTPUTS: The second replicate of our study was conducted during the second year of our project May to July 2011), approximately a year after the first replicate. All treatments, semen collections and evaluations, testicular ultrasound evaluations were performed the same way as in the first replicate. Blood samples were collected from all stallions four weeks prior to the treatment. One sample of blood was also collected immediately before administration of l-CDB-4022 or vehicle (time 0). Multiple samples of blood were taken during first 24 hours after treatment. Daily collections of blood samples were performed once a day for the next 13 days, and twice a week for the next 4 weeks. Testicular biopsies were taken one week before treatment, one day after treatment, two weeks after treatment, and four weeks after treatment. Two samples of testicular tissue were taken each time using the automatic 18 G tru-cut instrument (Temno, Bauer Medical Instruments, S.A.), as previously described. One sample of each biopsy was processed for histological evaluation, while the second one was snap frozen for the endocrine analysis. Plasma concentrations of testosterone, estradiol, estrogen conjugates, LH, FSH and inhibin are currently being measured by RIA assay in the Endocrinology Laboratory, University of California, Davis, as previously described. PARTICIPANTS: Malgorzata Pozor - PI; University of Florida, College of Veterinary Medicine; Study design, coordination, data collection; interpretation of data Margo Macpherson - Co-I; University of Florida, College of Veterinary Medicine; Study design,interpretation of data Sue McDonnell- Co-I: School of Veterinary Medicine, University of Pennsylvania; Analysis of behavioral data Janet Roser - Co-I: University of California, Department of Animal Science, #College of Veterinary Medicine; Analysis of endocrine samples and interpretation Charles Love - Co-I: College of Veterinary Medicine, T&M University; Analysis of Sperm Chromatine Structure Scott Runyon, Brian Thomas - Co-I; Research Triangle Institute, Research Triangle Park, NC; Provided the compund and helped in study design and interpretation of data Mats Troedsson - Co-I; College of Agriculture, University of Kentucky; Participated in study design and interpretation of data Rex Hess - Co-I; College of veterinary Medicine; University of Illinois; Analysis of histological samples (testicular biopsies) David Dymock - sugery resident; University of Florida, College of Veterinary Medicine; performing castrations Erin Runcan - resident; University of Florida, College of Veterinary Medicine; help in data collection Maggie Nollin - veterinary student; University of Florida, College of Veterinary Medicine; data collection and processing Gina Zambrano - veterinary student; University of Florida, College of Veterinary Medicine; data collection and processing Student workers: Christina Divine; Julia Dietz; Allie Wetzel; data collection and processing TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Based on the results of the first replicate of our study, we have increased frequency of collection of blood samples from all animals after the administration of the compund or placebo. One sample of blood was collected immediately before administration of l-CDB-4022 or vehicle. Multiple samples of blood were taken during first 24 hours after treatment (six hourly samples, and three samples taken every other hour. Daily collections of blood samples were performed once a day for the next 13 days, and twice a week for the next 4.5 weeks. We were awarded additional funding for analysis of these additional samples. This process is currently in progress.
Impacts
Similarily, as in the first replicate, semen parameters were severely affected by the single administration of l-CDB-4022 to the stallions in Group TREATED. We do not have the results of the endocrine assays from the second replicate of the study yet, except testosterone. Concentration of this hormone had a tendency to decrease in Group TREATED within 3 hours after the administration of the compound (P<0.1); then testosterone concentrations increased significantly, but transiently, by day five after treatment. While evaluation of tissue samples have not been completed yet, our preliminary observations suggest that a single administration of l-CDB-4022 had severe effects on seminiferous tubules in treated stallions, such as: disorganization of seminiferous tubules, immature round germ cells present in the lumen of seminferous tubules and in epididymal duct; collapse of seminiferous tubules, vacuolization of Sertoli cells and germ cells, decrease of numbers of layers in seminiferous tubules. There was only slight, but significant decrease in testicular volume in treated stallions, mostly due to a pronounced effect of the compound on a stallion with largest testes in Group TREATED in second replicate. Conclusion: Administration of a single oral dose of l-CDB-4022 to Miniature horse stallions produces similar changes to naturaly occuring, idiopathic testicular degeneration in horses. We conclude that this compound can be used to induce a suitable model of testicular degeneration in stallions to study the effects of various therapies for this condition.
Publications
- No publications reported this period
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Progress 04/01/10 to 03/31/11
Outputs
OUTPUTS: We have conducted our first experiment in this study. This experiment was done in the spring and summer months (April to August 2011), when horses have their physiological breeding season. Four weeks before treatment with a new male contraceptive l-CDB-4022 semen was collected from all stallions for five consecutive days in order to remove extragonadal sperm reserves. Ejaculates collected on the fifth day were also evaluated in order to establish a daily sperm output (DSO) for each animal. After this period (DSO I) semen was collected and evaluated twice a week, for three baseline weeks (BASELINE). In addition, the initial ultrasound evaluation of the scrotal testes was performed, and blood was drawn for the baseline endocrine analysis (two weeks before treatment). Then stallions were randomly assigned into two groups: Group TREATED (n=3) and Group CONTROL (n=3). Stallions in Group TREATED received a single dose of l-CDB-4022 (12.5 mg/kg dissolved in 60 mL of 10% EtOH; PO; Research Triangle Institute, NC); stallions from Group CONTROL received 60 mL of 10% EtOH, as a placebo treatment. This treatment was administered orally, using a dose syringe. Subsequently semen was collected and evaluated twice a week from all stallions for 12 consecutive weeks (POST-TREATMENT). Ultrasound evaluations of scrotal testes and blood draws were performed once a week during this period. Another series of five daily semen collections (DSO II) was performed during 13th week after treatment, in order to establish any long-term effects of treatment on sperm production in stallions. All semen collection sessions were recorded using a video camera mounted on a tripod (digital camera Sony HDR-XR550, equipped with the wide lens), and submitted for analysis in the Equine Behavior Lab, University of Pennsylvania School of Veterinary Medicine, New Bolton Center. Recorded material was viewed by one, trained behaviorist, who was blind to the treatment. Numerous behavioral endpoints were derived. Both testes were evaluated once a week throughout a study, using a portable ultrasound equipped with a 4-7 MHz curved array transducer (Tytan, SonoSite, Inc, Bothell, WA). The length, height, and width of each testicle were measured using B-mode ultrasonography to calculate the total testicular volume using the formula for ellipsoid volume [Vt=(4/3 Pi) (W/2)(H/2)(L/2); where W=width, H=height, and L=length]. A ten mL sample of blood was collected from the jugular vein of each stallion every week throughout the study in order to measure concentrations of the reproductive hormones. Plasma will be harvested and stored at -70 degrees C until the assays were completed. Plasma concentrations of testosterone, estradiol, estrogen conjugates, LH, FSH and inhibin were measured by RIA assay in the Endocrinology Laboratory, University of California, Davis. PARTICIPANTS: A team of investigators participated in this study. Dr.Sue McDonnell is a world renowned specialist in the reproductive behavior of horses and she performed the objective analysis of all behavioral data. Dr. Love established a method of analysis of sperm chromatin structure in his laboratory, and he performed perform this test on all semen samples collected during our experiment. All blood samples were sent for endocrine analysis to the Endocrinology Laboratory, California Davis, which has well validated methods of detecting concentrations of equine gonadotropins and reproductive steroids. Dr. Parekattil was a Director of Male Infertility and Microsurgery and a Professor of Urology in the College of Medicine, University of Florida. He has extensive experience in performing invasive testicular procedures in humans and he is our adviser on performing invasive procedures such as testicular biopsies from our experimental animals (this part of the experiment was not conduceted yet). Drs.Pozor, Macpherson, DeLuca and Diaw were directly involved in performing this study and they all have experience in this type of investigations. Dr.Troedsson participated in our previous studies and actively participated in preparing our study. He served as an adviser in the analysis of the data from this study. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
There were no changes in any of the behavioral endpoints during the experiment for any of the groups. There were no problems with collecting semen from any of the stallions, except a few instances when there were some technical difficulties with the equipment (artificial vagina). We have not observed any patterns in the overall efficiency of semen collection in any of the groups. All stallions showed an adequate sexual interest and a normal copulatory behavior throughout the experiment. There were no changes in the concentration of inhibin within any of the groups during this study. One stallion from Group CONTROL had unusually high concentration of inhibin throughout the study. This stallion had a very good quality of semen and normal concentrations of other reproductive hormones. Concentration of FSH increased in Group TREATED on day 17 after the administration of the compound (P<0.05). There was a sharp pick in the concentration of LH in Group TREATED three days after the administration of l-CDB-4022 (P<0.05). Testosterone concentration increased temporarily on day 24 after treatment. The concentrations of estradiol 17-beta fluctuated throughout the experiment in both groups, but these changes were significant only in Group TREATED. In addition, the ratio of testosterone to estradiol 17-beta increased on day 3 and 24 after treatment (P<0.05). This ratio had a tendency to decrease on day 52 and 80 after treatment (P=0.01). The results of the present study confirmed that l-CDB-4022 has a strong anti-spermatogenic effect in stallions. Severe oligoasthenozoospermia and high number of the immature germ cells appeared in semen of treated stallions two weeks after administration of a single dose of this compound. This is consistent with the results of similar studies on other species. In addition, spermatozoa with morphological defects such as bent tails as well as with tailess heads increased their numbers. These effects were fully reversible slowly decreasing until sperm numbers reached the pre-treatment levels, which occurred 10 weeks after treatment. These changes in semen parameters were accompanied by the gradual increase in FSH concentrations, however, testosterone concentrations or libido did not decrease. Interestingly, testicular perfusion initially decreased in treated animals (1st and 2nd week after treatment) and then significantly increased (4th and 5th week after treatment). All these findings provide strong evidence that a single administration of l-CDB-4022 can induce severe but reversible testicular dysfunction in stallions consistent with a process of testicular degeneration. The investigators learnt from these reults that l-CDB-4022 can be used to create a model of testicular degeneration in stallions. Further studies need to be done in order to learn about the meachanism of action of the compund. This question will be addressed in the second part of the study.
Publications
- No publications reported this period
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