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Pituitary-derived Follicle stimulating hormone has greater follicle-stimulating bioactivity than recombinant Follicle stimulating hormone possibly due to glycoform variants†

文献类型: 外文期刊

作者: Wu, Zihui 1 ; Sun, Nan 1 ; Tang, Jiabin 1 ; Xu, Linghua 1 ; Zhou, Xinrui 1 ; Jiang, Menglei 1 ; Cheng, Jiarui 1 ; Zhu, Xuedan 1 ; Liu, Miaoyu 1 ; Yang, Liguo 1 ; Davis, John S. 6 ; Hua, Guohua 1 ;

作者机构: 1.Huazhong Agr Univ, Coll Anim Sci & Technol, Key Lab Agr Anim Genet Breeding & Reprod, Minist Educ, Wuhan, Hubei, Peoples R China

2.Huazhong Agr Univ, Frontiers Sci Ctr Anim Breeding & Sustainable Prod, Wuhan, Hubei, Peoples R China

3.Hubei Hongshan Lab, Wuhan, Hubei, Peoples R China

4.Natl Ctr Int Res Anim Genet Breeding & Reprod, Wuhan, Hubei, Peoples R China

5.Chinese Acad Agr Sci, Agr Genom Inst Shenzhen, Guangdong Lab Lingnan Modern Agr,Minist Agr, Genome Anal Lab,Minist Agr,Shenzhen Branch, Shenzhen 518000, Peoples R China

6.Univ Nebraska Med Ctr, Olson Ctr Womens Hlth, Dept Obstet & Gynecol, Omaha, NE 68198 USA

关键词: FSH; glycoform; follicular development; pre-antral follicles; antral follicles; ovulation

期刊名称:BIOLOGY OF REPRODUCTION ( 影响因子:3.0; 五年影响因子:3.5 )

ISSN: 0006-3363

年卷期: 2025 年

页码:

收录情况: SCI

摘要: Follicle-stimulating hormone is the primary gonadotropin regulating ovarian follicular development and is widely utilized in assisted reproduction. Our previous research indicated that different glycoforms of the follicle-stimulating hormone Beta-subunit influence follicular development in vivo, but their specific roles across various folliculogenesis stages remained unclear. In this study, we compared two commercial follicle-stimulating hormone preparations: pituitary-derived follicle-stimulating hormone, which contains both fully and hypo- glycosylated Beta-subunit forms, and recombination follicle-stimulating hormone, predominantly consisting of fully glycosylated forms. Using an in vitro follicular culture model, we observed that pituitary-derived follicle-stimulating hormone was more effective than recombination follicle-stimulating hormone in stimulating follicular growth and promoting antrum formation in preantral follicles. Pituitary-derived follicle-stimulating hormone also rescued insufficient preantral follicle growth and antrum formation caused by recombination follicle-stimulating hormone. Besides, pituitary-derived follicle-stimulating hormone more efficiently drove small antral follicle growth than recombination follicle-stimulating hormone. Additionally, pituitary-derived follicle-stimulating hormone significantly increased the granulosa cells proliferation and effectively inhibited apoptosis, thereby protecting growing follicles from atresia. Pituitary-derived follicle-stimulating hormone also induced higher steroidogenesis than recombination follicle-stimulating hormone. Mechanistically, pituitary-derived follicle-stimulating hormone activated key downstream signaling including protein kinase A/cAMP-response element binding protein, mitogen-activated protein kinase/extracellular signal-regulated kinase, and phosphatidylinositol 3-kinase/AKT more efficiently than recombination follicle-stimulating hormone. Importantly, pre-treating antral follicles with pituitary-derived follicle-stimulating hormone significantly improved ovulation rate following human chorionic gonadotropin administration. This was linked to a rapid upregulation of luteinizing hormone/choriogonadotropin receptor expression and enhanced mitogen-activated protein kinase/extracellular signal-regulated kinase signaling activity. Collectively, our data support that pituitary-derived follicle-stimulating hormone, with its mixture of fully and hypo-glycosylated forms, has greater bioactivity in promoting preantral-antral transition, antral follicle growth, and ovulation compared to recombination follicle-stimulating hormone, which mainly consists of fully glycosylated follicle-stimulating hormone. Application of mixed glycoforms or hypo-glycosylated follicle-stimulating hormone may improve the outcomes in assisted reproduction. Sentence: Pituitary-derived FSH, a mixture of fully and hypo-glycosylated forms, has greater bioactivity in facilitating murine follicular development and ovulation in vitro compared to recombinant FSH which primarily contains fully glycosylated FSH.

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