Bioactivity and Pharmacodynamics of X002, A Follicle-Stimulating Hormone-IgG4 Fc Fusion Protein.

IF 1.3 4区 农林科学 Q2 VETERINARY SCIENCES
Guili Xu, Yi Yang, Yunhui Liu, Fang Chen, Lihou Dong, Deyou Wan, Hongjie Li, Cuima Yang, Xin Gao
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引用次数: 0

Abstract

Current follicle-stimulating hormone (FSH) drugs meet safety criteria but have suboptimal efficacy, poor patient compliance, and high cost. Alternative FSH-like drugs would help to meet the high market demand. Here, we evaluated X002, an FSH-Fc fusion protein, for bioactivity and half-life in vitro and in vivo. In all cases, the effects of X002 were compared with those of a commercially available short-acting FSH recombinant hormone. First, female Kunming mice (age, 21 to 24 d) were stimulated with pregnant mare serum gonadotropin (PMSG) for 46 h, after which naked oocytes were harvested, treated with X002 or the comparison agent at 37 °C for 4 h, and then evaluated for germinal vesicle breakdown. Second, cumulus-oocyte complexes (COC) were collected from PMSG-stimulated mice and cocultured with X002 or the comparison agent for 14 h; the COC diameters were then measured, and the expression of genes involved in COC expansion were evaluated using quantitative RT-PCR analysis. Third, to assess the pharmacokinetics of X002, female Sprague-Dawley rats (age, 6 to 8 wk) were injected subcutaneously with X002 or the comparison agent; serum samples then were collected at various times and assessed via ELISA. Fourth, to evaluate X002 pharmacodynamics, 26-d-old female Sprague-Dawley rats were treated with X002 or the comparison agent; 84 h later, the rats were stimulated with human chorionic gonadotropin (hCG). At 12 h after hCG injection, euthanasia was performed. Ovaries were removed and weighed, and serum levels of estradiol and progesterone were measured. Finally, to assess superovulation, the oocytes in the fallopian tubes were counted at 108 h after in vivo treatment of rats with X002 or the comparison agent. The data show that X002, a long-acting agent, promoted germinal vesicle breakdown and COC expansion in vitro and in vivo ovarian weight gain and superovulation to a degree similar to the short-acting comparison agent.

X002的生物活性和药效学,一个卵泡刺激激素IgG4-Fc融合蛋白。
目前的卵泡刺激素(FSH)药物符合安全标准,但疗效不佳,患者依从性差,成本高。替代类FSH药物将有助于满足高市场需求。在这里,我们评估了X002,一种FSH-Fc融合蛋白,在体外和体内的生物活性和半衰期。在所有情况下,将X002的效果与市售的短效FSH重组激素的效果进行比较。首先,用孕马血清促性腺激素(PMSG)刺激雌性昆明小鼠(年龄,21-24天)46小时,然后收获裸卵母细胞,用X002或对照剂在37°C下处理4小时,然后评估生发泡破裂。其次,从PMSG刺激的小鼠中收集卵丘-卵母细胞复合物(COC),并与X002或对照剂共培养14小时;然后测量COC直径,并使用定量RT-PCR分析评估参与COC扩增的基因的表达。第三,为了评估X002的药代动力学,雌性Sprague-Dawley大鼠(年龄,6-8周)皮下注射X002或对照剂;然后在不同时间收集血清样品并通过ELISA进行评估。第四,为了评价X002的药效学,用X002或对照剂治疗26日龄雌性Sprague-Dawley大鼠;84小时后,用人绒毛膜促性腺激素(hCG)刺激大鼠。在注射hCG后12小时,进行安乐死。取出卵巢并称重,测量血清雌二醇和孕酮水平。最后,为了评估超排卵,在用X002或对照剂对大鼠进行体内治疗后108小时,对输卵管中的卵母细胞进行计数。数据显示,X002是一种长效制剂,在体外和体内促进生发囊泡破裂和COC扩张,卵巢增重和超排卵的程度与短效对照剂相似。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Comparative medicine
Comparative medicine 医学-动物学
CiteScore
1.90
自引率
0.00%
发文量
71
审稿时长
6-12 weeks
期刊介绍: Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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