Superovulation with a single administration of FSH in aluminum hydroxide gel: a novel superovulation method for cattle

Abstract

Superovulation (SOV) is a necessary technique to produce large numbers of embryos for embryo transfer. In the conventional methods, follicular stimulating hormone (FSH) is administered to donor cattle twice daily for 3 to 4 days. As this method is labor intensive and stresses cattle, improving this method has been desired. We previously developed a novel and simple SOV method, in which the intramuscular injection of a single dose of FSH in aluminum hydroxide gel (AH-gel) induced the growth of multiple follicles, ovulation and the production of multiple embryos. Here we show that AH-gel can efficiently adsorb FSH and release it effectively in the presence of BSA, a major interstitial protein. When a single intramuscular administration of the FSH and AH-gel mixture was performed to cattle, multiple follicular growth, ovulation and embryo production were induced. However, the treatments caused indurations at the administration sites in the muscle. To reduce the muscle damage, we investigated alternative administration routes and different amounts of aluminum in the gel. By administering the FSH in AH-gel subcutaneously rather than intramuscularly, the amount of aluminum in the gel could be reduced, thus reducing the size of the induration. Moreover, repeated administrations of FSH with AH-gel did not affect the superovulatory response. These results indicate that a single administration of FSH with AH-gel is an effective, novel and practical method for SOV treatment.

Ovarian responses and FSH profiles at superovulation with a single epidural administration of gonadotropin in the Thai-Holstein crossbreed

“…However, multiple injections of FSH are required due to its short half-life, which is time-consuming and may also be stressful for the cows (Sugano and Shinogi, 1999;Chasombat et al, 2013). Many previous studies proposed solving this issue by administering FSH dissolved in various agents that provide a slow release, such as polyvinylpyrrolidone (PVP) (Yamamoto et al, 1994;Takedomi et al, 1995;Ratsiri et al, 2021) and aluminium hydroxide gel (AH-gel) in cattle (Kimura, 2016). However, those diluting agents make the solution viscous and difficult to prepare well with FSH.…”

Superovulation in cattle – searching for the optimal dose, alternative routes of administration and a simplified FSH application program

“…Despite satisfying results (a large number of corpora lutea and transferable embryos collected), PVP seemed to be an adjuvant with some defects. The FSH suspension in PVP characterized with high viscosity, which created some difficulties to achieve a homogeneous mixture and limited its practical application (6,23). However, as no other undesirable effects have been demonstrated, PVP is still used in some countries as an adjuvant in commercial FSH preparations (10).…”

“…It was shown that for cattle receiving single intramuscular doses of 30 mg of pFSH with 5 ml of aluminum hydroxide gel, the number of corpora lutea, the total number of ova and the number of transferable embryos collected did not differ significantly from the conventional pFSH treatment. However, the disadvantage of AH-gel applied intramuscularly were pathological changes in the site of administration in the form of granulomas and swelling accompanied by a significant accumulation of macrophages, monocytes and giant cells (23). These pathological changes at the place of injection in meat cattle caused significant economic losses and growing consumer dissatisfaction.…”

“…For this reason, other routes of administration of FSH were searched for. It was hypothesized that subcutaneous administration would provide the possibility to decrease the amount of Aluminum contained in AH-gel and consequently reduce adverse reactions (23).…”

Recent progress in bovine in vitro‐derived embryo cryotolerance: Impact of in vitro culture systems, advances in cryopreservation and future considerations

“…Although some people feel that large offspring syndrome may be relegated Current donor follicle stimulation protocols require multiple daily injections due to the relative short half-life FSH preparation in the female blood circulation. Current strategies to overcome this labour-intensive situation are based on using long-acting FSH analogs through a slow release formulation (Kimura, 2016), or even more desirable, replacing pituitary-derived preparations with recombinant bovine FSH (Carvalho et al, 2014). Promising research developments in the near future will likely be associated with bovine recombinant FSH for donor stimulation (Hesser, Morris, & Gibbons, 2011).…”