The glycan structure in recombinant human FSH affects endocrine activity and global gene expression in human granulosa cells

The aim of this study was to analyse the biological response to different recombinant human FSH (rhFSH) glycosylation variants on the endocrine activity and gene expression at whole-genome scale in human granulosa-like tumor cell line, KGN. The effects of differences in rhFSH sialylation and oligosaccharide complexity were determined on steroid hormone and inhibin production. A microarray approach was used to explore gene expression patterns induced by rhFSH glycosylation variants. Set enrichment analysis revealed that hormone sialylation and oligosaccharide complexity in rhFSH differentially affected the expression of genes involved in essential biological processes and molecular functions of KGN cells. The relevance of rhFSH oligosaccharide structure on steroidogenesis was confirmed assessing gene expression by real time-PCR. The results demonstrate that FSH oligosaccharide structure affects expression of genes encoding proteins, growth factors and hormones essential for granulosa cells function.

► FSH sialylation and its oligosaccharides complexity differentially affected endocrine activity.
► Global gene expression was differentially regulated by rhFSH glycoforms.
► Set enrichment analysis revealed that rhFSH glycoforms modulate relevant functions in granulosa cells.
► FSH sialylation and oligosaccharide complexity differentially affected gene expression of steroidogenic enzymes.