Gene expression analysis of ovarian follicles and stromal cells in girls with Turner syndrome

Abstract In patients with mosaic Turner syndrome, the ovarian somatic cells (granulosa and stromal cells) display a high level of aneuploidy with a 45,X karyotype, which may affect gene expression in the ovary and contribute to their reduced fertility. The aim of the current research is to study the effect of aneuploidy of somatic ovarian cells on gene expression in ovarian cortex stromal cells and small ovarian follicles from mosaic (45,X/46,XX) Turner syndrome patients. To this end, ovarian cortical tissue was obtained by laparoscopic surgery from eight mosaic Turner syndrome patients (aged 5–19 years) and eight controls (aged 6–18 years). The tissue was fractionated to obtain purified follicles and stromal cells. Part of the purified fractions was used to determine the X chromosomal content of ovarian cells of Turner syndrome patients by interphase FISH, while the remaining part was used to compare the gene expression profile of these cells to controls. The results demonstrated that high level 45,X haploidy in cortical stromal cells of Turner syndrome patients had no effect on gene expression, gross morphology of the ovary, or histological appearance of the cortex compared to controls. Gene expression analysis of purified small follicles of Turner syndrome patients with mainly 45,X granulosa cells revealed aberrant expression of 11 genes. Of these, six were upregulated (CD24, TLR1, EPHA2, PLXND1, ST6GALNAC5, and NOX4) while five genes (CRYAB, DLX1, PCYT2, TNFRSF8, and CA12) were downregulated compared to follicles of controls. Interestingly, the overexpressed genes in these small follicles were all associated with more advanced stages of follicular development. The consequences of this abnormal gene expression in follicles for Turner syndrome patients remain to be investigated, but they are likely to affect fertility.