Departamento de Ciencias Clínicas, Facultad de Veterinaria, Universidad de Concepción, Chile.
Departamento de Farmacología, Universidad de Concepción, Chile.
Theriogenology. 2024 Sep 15;226:76-86. doi: 10.1016/j.theriogenology.2024.05.038. Epub 2024 May 29.
Assisted reproduction is a key aspect of modern animal breeding, providing valuable assistance in improving breeding programs. In this field, the administration of exogenous hormones, such as follicle-stimulating hormone (FSH), plays a crucial role in the induction of multiple ovulations. However, commercial FSH used in veterinary practice has been derived primarily from pituitary glands, obtained mostly from pigs for nearly four decades. Although these hormones have contributed significantly to the advancement of assisted reproductive techniques, they have certain limitations that warrant further improvements. These limitations include contamination with luteinizing hormone (LH), the potential risk of pathogen contamination, the potential to trigger an immune response in non-pig species, and the short half-life in circulation, requiring the implementation of complex 8-dose superovulation schedules. Our research team has developed and characterized a new variant of bovine follicle-stimulating hormone (bscrFSH) to address these limitations. The new hormone is produced recombinantly in CHO cell cultures, with a specific productivity of about 30 pg/cell/day. The bscrFSH can be purified to a high purity of 97 % using a single step of immobilized metal affinity chromatography (IMAC). N-glycan analysis of bscrFSH showed that approximately 74 % of the glycans corresponded to charged structures, including mono-, di-, tri-, and tetra-sialylated glycans. Superovulation trials conducted in cattle revealed that bscrFSH, administered at a total dose of about 0.5 μg per kg of body weight, using a decrescent schedule of 4 doses with 24-h intervals, resulted in an average yield of 8-12 transferable embryos per animal. Further research is required; however, the preliminary findings indicate that bscrFSH, currently packaged under the provisional brand name of Cebitropin B, holds potential as a commercial product for assisted reproduction in ruminants.
辅助生殖是现代动物繁殖的一个关键方面，为改进繁殖计划提供了有价值的帮助。在这个领域，外源性激素（如促卵泡激素（FSH））的管理在诱导多次排卵中起着至关重要的作用。然而，兽医实践中使用的商业 FSH 主要来源于垂体，近四十年来，这些激素主要从猪中获得。尽管这些激素为辅助生殖技术的进步做出了巨大贡献，但它们存在一定的局限性，需要进一步改进。这些局限性包括与黄体生成素（LH）的污染、潜在的病原体污染风险、在非猪物种中引发免疫反应的潜力以及在循环中的半衰期短，需要实施复杂的 8 剂量超排卵方案。我们的研究团队开发并表征了一种新的牛促卵泡激素（bscrFSH）变体，以解决这些局限性。新激素通过 CHO 细胞培养进行重组生产，特定产率约为 30pg/细胞/天。bscrFSH 可以使用固定化金属亲和层析（IMAC）的单一步骤纯化到 97%的高纯度。bscrFSH 的 N-糖基分析表明，大约 74%的聚糖对应于带电结构，包括单、二、三、四唾液酸化聚糖。在牛中进行的超排卵试验表明，bscrFSH 以约 0.5μg/公斤体重的总剂量，使用递减方案，4 次剂量，间隔 24 小时，每头动物的平均产率为 8-12 个可转移胚胎。还需要进一步研究；然而，初步研究结果表明，bscrFSH 目前以暂定品牌名称 Cebitropin B 包装，作为反刍动物辅助生殖的商业产品具有潜力。
