Development of a Long-Acting Follicle-Stimulating Hormone Using Serum Albumin Fab-Associated Technology for Female Infertility

Daham Kim; Yoon Hee Cho; Min Jeong Kang; So Jeong Lee; Soohyun Lee; Bo Hyon Yun; Hyunjin Chi; Jeongsuk An; Kyungsun Lee; Jaekyu Han; Susan Chi; Moo Young Song; Sang-Hoon Cha; Eun Jig Lee

doi:10.3803/enm.2024.2090

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Development of a Long-Acting Follicle-Stimulating Hormone Using Serum Albumin Fab-Associated Technology for Female Infertility

Authors: Daham Kim ; Yoon Hee Cho ; Min Jeong Kang ; So Jeong Lee ; Soohyun Lee ; Bo Hyon Yun ; Hyunjin Chi ; Jeongsuk An ; Kyungsun Lee ; Jaekyu Han ; Susan Chi ; Moo Young Song ; Sang-Hoon Cha ; Eun Jig Lee

Citation: Endocrinology and Metabolism (대한내분비학회지), Vol.40(1) : 146-155, 2025-02

Journal Title: Endocrinology and Metabolism(대한내분비학회지)

ISSN: 2093-596X

Issue Date: 2025-02

MeSH: Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Cyclic AMP / metabolism ; Estradiol / blood ; Female ; Follicle Stimulating Hormone* / pharmacology ; Follicle Stimulating Hormone* / therapeutic use ; Humans ; Infertility, Female* / drug therapy ; Ovary / drug effects ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins / pharmacology ; Serum Albumin* ; Steroidogenic Acute Regulatory Protein

Keywords: Female infertility ; Follicle stimulating hormone ; Gonadotropins ; Ovulation

Abstract: Backgruound: Recombinant human follicle-stimulating hormone (rhFSH) is commonly used to treat female infertility, but its short half-life necessitates multiple doses. Even corifollitropin alfa, with an extended half-life, requires supplementary injections of rhFSH after 7 days. This study aimed to develop and evaluate a long-acting follicle-stimulating hormone (FSH) formulation using anti-serum albumin Fab-associated (SAFA) technology to avoid additional injections and enhance ovarian function.

Methods: SAFA-FSH was synthesized using a Chinese hamster ovary expression system. Its biological efficacy was confirmed through assays measuring its ability to stimulate cyclic adenosine monophosphate (cAMP) production, estradiol synthesis, and the expression of human cytochrome P450 family 19 subfamily A member 1 (hCYP19α1) and human steroidogenic acute regulatory protein (hSTAR) in human ovarian granulosa (KGN) cells. To evaluate the effects of SAFA-FSH, we compared its impact on serum estradiol levels and ovarian weight increase with that of rhFSH in Sprague-Dawley (SD) rats using the modified Steelman-Pohley test.

Results: The results indicated that SAFA-FSH induces cAMP synthesis in KGN cells and upregulates the expression of hCYP19α1 and hSTAR in a dose-dependent manner. Female SD rats, aged 21 days, receiving daily subcutaneous human chorionic gonadotropin injections for 5 days exhibited a significant increase in serum estradiol levels and ovarian weight when administered SAFA-FSH on the first day or when given nine injections of rhFSH over 5 days. Notably, the group receiving SAFA-FSH on the first and third days demonstrated an even greater rise in serum estradiol levels and ovarian weight.

Conclusion: These findings suggest that SAFA-FSH presents a promising alternative to current rhFSH treatments for female infertility. However, further research is essential to thoroughly assess its safety and efficacy in clinical contexts.