What is it about?

Hormones are tiny biological signals, yet they play a decisive role in fertility and the creation of new life. Among them, follicle-stimulating hormone (FSH) is essential for follicular development, ovulation, and normal reproductive function. Although conventional FSH has long been used in reproductive medicine and fertility research, its effectiveness can still be limited by short biological activity and the need for repeated administration. In this study, we engineered a novel single-chain FSH (sc-hFSH LNN) by linking the two FSH subunits into one continuous molecule and introducing additional LNN N-glycosylation sites to improve stability and biological performance. Using ICR mice as an in vivo model, we evaluated how this engineered hormone influences reproductive organs, hormonal responses, and fertility outcomes. The findings revealed that sc-hFSH LNN is biologically active and capable of strongly stimulating reproductive function. A single injection produced greater effects than multiple split doses, while the highest response was observed at 5 µg/mL. Most importantly, pre-mating treatment significantly improved pregnancy rates and increased litter sizes in adult female mice, suggesting enhanced follicular maturation and ovulation. By combining protein engineering with reproductive biology, this work highlights the potential of single-chain FSH as a next-generation reproductive biopharmaceutical. Beyond its scientific value, the study opens promising opportunities for improving fertility treatments and advancing future applications in reproductive medicine and biotechnology.

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Why is it important?

This study is important because it demonstrates the potential of protein engineering to improve the effectiveness of reproductive hormones. By developing a novel single-chain FSH with additional LNN glycosylation sites, the research provides evidence that structural modification can enhance hormone stability and biological activity in vivo. The ability of sc-hFSH LNN to improve reproductive responses, pregnancy rates, and litter sizes highlights its promise as a next-generation gonadotropin for reproductive biology and fertility-related applications. These findings may contribute to the future development of more efficient and patient-friendly biopharmaceuticals in reproductive medicine and animal biotechnology.

Perspectives

Our study demonstrated promising biological activity of sc-hFSH LNN in live animals and improved reproductive outcomes in mice, but further studies are needed before clinical or commercial application. Future research will focus on detailed pharmacokinetic and pharmacodynamic characterization, receptor binding affinity, long-term safety, and immunogenicity assessment. Comparative studies in larger animal models and assisted reproductive systems will also be crucial to confirm its therapeutic potential. Additionally, optimization of large-scale recombinant production, purification processes, formulation stability, and regulatory quality standards will be essential for the development of this biopharmaceutical. We hope that with continued progress, sc-hFSH LNN could represent a next-generation gonadotropin with improved efficacy, reduced dosing frequency, and wider applications in reproductive medicine and animal biotechnology.

Assoc. Prof. Dr. NGUYEN Thi Mong Diep
Quy Nhon University

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This page is a summary of: Single-chain human Follicle-stimulating hormone promotes ovarian and testicular growth and improves pregnancy performance in mice, PLOS One, May 2026, PLOS,
DOI: 10.1371/journal.pone.0349398.
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