Researchers have found that phenylbutazone, a commonly used non-steroidal anti-inflammatory drug (NSAID) for horses, has a negative impact on the maturation of mare’s egg cells, or ‘oocytes,’ which is essential for creating viable embryos during assisted reproduction in horses.
Researchers at the Texas A&M School of Veterinary Medicine & Biomedical Sciences (VMBS) have found that phenylbutazone, a frequently prescribed non-steroidal anti-inflammatory drug (NSAID) for horses, can influence the capability of a mare’s egg cells, known as “oocytes,” to develop into viable embryos. This process is vital for successful assisted reproduction in horses.
This important finding, recently published in the journal Theriogenology, is noteworthy due to the significant time and financial investment horse owners often make in assisted reproduction.
Similar to humans, horses may sometimes require scientific assistance to reproduce. Because of the unique characteristics of equine sex cells, specialized procedures are necessary for a successful pregnancy.
“The in-vitro fertilization (IVF) procedure in horses is more intricate than it is in humans,” noted Dr. Luisa Ramirez-Agamez, a Ph.D. candidate in VMBS’ Department of Large Animal Clinical Sciences (VLCS), who is researching equine reproduction. “Firstly, a mare’s oocytes need about 30 hours to mature in the lab after being collected before they can be fertilized. After that, we must inject the eggs with sperm through a method called Intracytoplasmic Sperm Injection (ICSI).
“We found that phenylbutazone, often referred to as bute, can influence both the maturation of a mare’s eggs during culture and whether the fertilized eggs can turn into viable embryos,” she explained. “In either case, eggs affected by bute cannot be utilized for assisted reproduction.”
The Importance of Equine Assisted Reproduction
Assisted reproduction serves as a crucial tool for many horse owners, particularly those who depend on their herds for income. Additionally, many horse owners are passionate about producing offspring from their beloved horses to perpetuate their legacies.
In certain situations, mares that are permanently lame and cannot carry a pregnancy may still contribute as egg donors. Their eggs can be fertilized in a laboratory and later carried to term by a surrogate.
“This is one specific scenario affected by our findings,” said Ramirez. “Mares that are chronically lame often rely on bute for pain relief, particularly for issues in their musculoskeletal system, which our results indicate can hinder their eligibility for assisted reproduction programs.”
“In future research, we aim to identify an alternative to bute that provides similar pain relief without interfering with reproductive functions,” she added.
Fortunately, the impact of bute on equine oocytes seems to diminish after a few weeks.
“We gathered eggs at three days post-treatment, then again at 33 days, and finally at 77 days,” she explained. “Our findings showed that eggs collected three days following bute administration couldn’t produce embryos, but those retrieved at 33 days were viable. We hope to provide a more precise understanding of how bute affects egg cell quality in subsequent studies.”
Potential Implications for Human Medicine
Looking ahead, Ramirez is interested in collaborating with human medicine researchers due to the possible implications of her findings for IVF in women.
“NSAIDs are frequently administered to women during IVF to delay their ovulation cycle, which is the ovaries’ natural egg release each month,” she clarified. “Ordinarily, most women produce just one egg each month, but due to the high costs and time demands of IVF, women are given hormones to stimulate the production of multiple eggs each cycle. This ensures there are several eggs available for collection. NSAIDs can help prevent early ovulation, allowing women to retain those eggs.”
However, following her recent discoveries regarding NSAIDs and equine reproduction, Ramirez is curious about whether NSAIDs could also have unrecognized adverse effects on IVF.
“NSAIDs are generally considered beneficial for IVF in women; however, our findings imply that these medications may not be harmless for reproduction in horses,” she noted. “Some NSAIDs, like Banamine, can actually create non-ovulating follicles in horses—follicles that fail to release eggs as intended during ovulation.
“This situation does not occur in women, leading to the belief that NSAIDs are safe. But now we understand that bute can prevent fertilized eggs from progressing to embryos, raising the possibility that certain NSAIDs could exhibit a similar effect in women,” she remarked. “This is something I intend to explore further.”
