Single-chain human gonadotropin analogs induce follicle development in sheep

The biopotency of single-chain analogs of human hFSH, human chorionic gonadotropin (hCG), and a dually active gonadotropin construct (FcCGβα) was examined. Sheep (bwt=61.4±1.1 kg; n=6 ewes/treatment) received a single injection (5 IU/kg, i.v.) of the hFSH analog (Fcα), the hCG analog (CGβα), FcCGβα, or Fcα and CGβα. Control animals received conditioned media. Ovulation was induced 3 days after analog administration using hCG (1000 IU, i.v.). Basal serum concentrations of estradiol (E₂) were maintained in control animals. Neither Fcα nor CGβα alone induced significant E₂ production during the pre-hCG period. Conversely, serum concentrations of E₂ were increased (P<0.05) 2 days after administration of FcCGβα or Fcα + CGβα. Although P₄ concentrations were maintained at basal levels in control animals, significant increase was noted in all other treatment groups during the post-hCG period. Final ovarian weight was significantly increased (P<0.05) in animals receiving Fcα, Fcα + CGβα, or FcCGβα, but not CGβα alone. Most of the ovarian enlargement was attributed to the formation of corpora lutea. Collectively, these observations demonstrate that the single-chain analogs of the human gonadotropins are active in sheep. The construct with singular FSH activity supports follicle development but not E₂ production. Conversely, the construct that incorporates β-domains from both CG and FSH has dual activity. The long-lived nature of the single-chain constructs suggests that these recombinant gonadotropins may be effective alternatives to pituitary- or placenta-derived gonadotropins in out-of-season breeding and/or superovulation protocols.