Age-related testicular degeneration is a common problem in older stallions. This type of testicular degeneration is different than the degeneration that can be seen after, for example, an injury to the testes in a younger stallion. Following testicular trauma, many stallions are able to fully recover. However, age-related testicular degeneration results in progressive deterioration of the testes and an associated progressive decline in testicular function. Over time, affected stallions become progressively more subfertile and eventually may become sterile in association with decreases in semen quality, sperm numbers and testicular size. There is no proven treatment for age related testicular degeneration, although many therapies have been tried. In this article, Dr. Regina Turner of the New Bolton Center at the University of Pennsylvania, discusses the causes of age-related testicular degeneration, current research and how one can manage the breeding career of an aged stallion until a treatment or cure is found.
This problem is very important in the equine industry because genetically valuable stallions often are asked to continue breeding well into old age. Economic losses caused by age-related declining fertility can be substantial and result from losses of breeding fees, increases in mare and stallion management costs, and losses of valuable male genetics. There also can be significant human emotional upset when the problem occurs in a much-loved and highly successful breeding stallion. Yet in spite of its impact, we know very little about the underlying causes of age-related testicular degeneration in the horse, in part because the problem is so difficult to study in this species. The significant genetic variation among different stallions as well as the differences in how stallions are fed, housed, exercised, and managed all make carefully controlled studies of what is likely to be a multigenic, complex disease process very difficult to perform.
Cause of Testicular Degeneration in the Aged Stallion
Research in our lab, supported by the Grayson Jockey Club Research Foundation, has shown that the defect that is causing the degeneration of the testes in old horses lies within the cells of the testes themselves, and not within the larger hormonal environment in which the testes are supported. As might be expected if the testis itself is defective, the condition does not improve following treatment with substances designed to stimulate testicular function (e.g. hormone supplements and nutraceuticals). We hypothesized that, if the problem lies with the aged testis cells themselves, then one would need to restore young cells to the old, degenerate testis to have a positive effect on sperm development. In essence, we would need to recreate a young cellular support system for the aged sperm producing cells.
Research Performed on Age Related Testicular Degeneration
In this regard, we have performed experiments in which we have grafted testicular supporting and steroid producing cells from young, healthy stallion testicular tissue into aged, degenerate stallion testicular tissue and have found that the presence of the young cells can improve the survival of the aged sperm producing cells. This improvement is small, but is noticeable and strongly suggests that the young testis cells (or some substance that these cells are producing) are supporting the aged sperm producing cells. If our data proves to be correct, this could lead to the development of a cell-based (e.g. stem cell) treatment for the disorder.
In an attempt to determine what is different between young testis cells and old testis cells (and so hopefully determine what it is about the young testis cells that is beneficial to old cells), we performed large-scale sequencing of all the genes expressed in the normal, fertile stallion testis and the aged, degenerate stallion testes. We found over 500 genes that were expressed differently in the young and old testicular tissue and are just beginning to wade through this list to identify genes that are candidates either for the cause of the problem or for a treatment for the problem. So far, it appears that most of these differentially expressed genes originate from the supporting and steroid producing cells of the testis. Genes originating from the spermatogonial stem cells (the stem cells that are responsible for forming sperm) seem relatively less affected. This is exciting because it suggests that, if we can provide young supporting cells to aged spermatogonial stem cells, we might be able to develop a cell-based therapy that could slow down or potentially even reverse the problems of decreased semen quality and decreased sperm numbers that are seen in age-related testicular degeneration in stallions.
Ways to Manage the Breeding Career of an Aged Stallion
As of now, this is only a hope and remains far from reality. There is no magic bullet that can correct the problem of aging in a stallion’s testicles. So until some type of potentially cell-based therapy can be developed, we are left with the approach of managing our aging stallions to try and preserve fertility in the face of declining testicular function. Management techniques that may help improve the reproductive efficiency of affected stallions include breeding mares as close to ovulation as possible and as close to the sight of fertilization as possible (deep horn insemination), and limiting the book size of affected stallions so that ejaculation frequency is reduced and sperm numbers are maximized.
Additionally, there is some evidence to suggest that sperm processing techniques can be used to improve the fertility of affected stallions. For example special gradients can be used to separate ‘good quality’ sperm from ‘poor quality’ sperm thus allowing us to breed each mare with semen that is enriched in sperm that are likely to be more fertile. In severe cases, intracytoplasmic sperm injection (ICSI) can be performed. ICSI (photo left) involves recovering individual oocytes (eggs) from the ovaries of the mare, then injecting each egg with a single sperm from the stallion. The ‘fertilized’ egg is then cultured in the laboratory and, if an embryo is produced, the embryo is transferred to a surrogate mare to produce a pregnancy. This technique can be quite expensive, but can result in pregnancies from stallions that are producing very low numbers of normal sperm. Another excellent management tip is to freeze sperm from fertile stallions while they are younger and before this problem begins. Banking frozen semen while a stallion is highly fertile remains the best and most cost-effective way of insuring that a genetic safety net is created in case age-related testicular degeneration sets in.
So far, a testicular fountain of youth remains elusive. The problem of aging in all tissues is extremely complex, involving many organ systems and cell types, and numerous genetic and environmental causes. Nonetheless, with the development of large scale genetic testing and cell-based/stem cell therapies, there is hope that in the future we may be able to delay or even prevent the adverse effects that aging has on sperm-producing cells and so preserve the fertility of our stallions into advanced old age.
If you like this article you may also be interested in reading: