Impaired Gremlin 1 (GREM1) expression in cumulus cells in young women with diminished ovarian reserve (DOR)

A symbiotic relationship between ovarian granulosa cells (GC) and the developing oocyte is critical. Genetic modulations in GC's can lead to reproductive insufficiency, highlighting the role of GC's in reproductive competence. Utilizing gene expression analyses in cumulus GC's, we attempt to enhance our understanding of mechanisms that may contribute to poor reproductive capacity in young women with diminished ovarian reserve (DOR). We measured gremlin 1 (GREM1) gene expression in GC's from infertile women < 38 years undergoing in vitro fertilization in the context of DOR. GREM1, a member of the differential screening-selected gene aberrative in neuroblastoma (DAN) family of genes known for its highly regulated expression pattern during folliculogenesis and a downstream effecter of oocyte-derived growth and differentiation factor 9, was down-regulated 3-fold (-3.08) in women with DOR versus control; down-regulation was confirmed by qRT-PCR (-4.02). This is the first demonstration linking differential expression of Gremlin with etiology of infertility in women.