Friday, August 23, 2024

Adverse effect of bute on assisted reproduction in mares

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 Phenylbutazone (“bute”) may not be as harmless for breeding animals as previously thought.

 Recent research from the USA indicates that bute can interfere with oocyte maturation and development after fertilization when assisted reproduction techniques are used.

 

While Thoroughbred mares often start breeding young, many other mares only begin breeding after a long working life. Many of these mares retire from work or start breeding due to orthopaedic problems that limit their performance and require regular NSAID treatment.

 

Researchers at the Texas A&M School of Veterinary Medicine & Biomedical Sciences (VMBS) have found that phenylbutazone, a non-steroidal anti-inflammatory drug (NSAID) commonly prescribed in horses, can affect a mare’s egg cells (oocytes), hindering their ability to mature into viable embryos, which is crucial for assisted reproduction.

 

The study, led by Dr Luisa Ramírez-Agámez and colleagues, looked at the effect of bute on the developmental competence of in vitro-matured equine oocytes subjected to Intracytoplasmic Sperm Injection (ICSI). Their findings are published in the journal Theriogenology.

 

In a press release, Ramírez-Agámez explained: “Mare’s oocytes need approximately 30 hours to mature in the laboratory once they have been collected before they can be fertilized. Then, we have to inject the eggs with sperm to induce fertilization, a process known as Intracytoplasmic Sperm Injection (ICSI).

 

“We discovered that phenylbutazone, commonly known as bute, can affect both the ability of a mare’s eggs to mature correctly when cultured and whether the fertilized eggs will develop into a viable embryo. In either of those cases, the eggs affected by bute cannot be used in assisted reproduction.”

 

In a preliminary study, the research team compared cumulus-oocyte-complexes (COCs) harvested from two mares treated with bute for 10 days before collection with those from four untreated mares. (The term "cumulus-oocyte complex" (COC) refers to an oocyte and the surrounding cumulus cells within the follicle. The cumulus cells are essential for the oocyte's development and maturation, providing nutrients and signals, and aiding in fertilization and embryo development.)

 

They found that oocyte in vitro maturation and blastocyst rates were lower in bute-treated mares compared to the control mares.

 

In the main experiment, nine healthy mares received a daily dose of bute (4.4 mg/kg, orally, once a day) for 10 days, while ten control mares received a placebo.

 

The researchers performed ultrasound-guided transvaginal oocyte aspiration (TVA) on days 3, 33, and 77 following the last dose of bute. The COCs recovered from both groups were matured in vitro and subjected to ICSI.

 

They observed that while the in vitro oocyte maturation rate was similar between the bute and control groups, oocyte recovery, cleavage, and blastocyst rates were significantly lower in the bute-treated group. However, these effects were short-lived, as by 33 and 77 days post-treatment, in vitro maturation, cleavage, and blastocyst rates were similar between the two groups.

 

“In a future study, we hope to determine an alternative to bute that supplies the same level of pain management but does not interfere with reproduction,” she added. “The good news is that bute’s effect on equine oocytes appears to wear off within a few weeks.

 

“We found that eggs collected three days after administration of bute were not able to produce embryos, but those collected at 33 days were successful. We hope to find a more exact answer in terms of how bute affects egg cell quality in a future study.”

 

 

For more details, see:

 

Ramírez-Agámez L, Hernández-Avilés C, Whitfield-Cargile CM, Coleman MC, Love CC. 

Treatment of mares with the non-steroidal anti-inflammatory drug (NSAID) phenylbutazone transiently affects in vitro maturation of equine oocytes and blastocyst development after Intracytoplasmic Sperm Injection (ICSI). 

Theriogenology (2024) 223:53-58.

https://doi.org/10.1016/j.theriogenology.2024.04.017

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