Ovarian function and X chromosome tissue mosaicism in adolescents with Turner syndrome and ongoing spontaneous...

The maintenance of normal ovarian function depends on the presence of two structurally intact X chromosomes, which explains the high risk of premature ovarian insufficiency in individuals with Turner syndrome (TS). Most aneuploid germ cells undergo apoptosis during embryonic gonadal development, resulting in the formation of streak gonads in the majority of individuals with a 45,X karyotype. However, the role of X-monosomy in ovarian somatic cells, which provide the microenvironment essential for oocyte survival and development, remains poorly understood. To our knowledge, this is the first study to investigate the association between X chromosome aneuploidy in ovarian somatic cells and peripheral blood lymphocytes and ovarian function in adolescents with mosaic TS. The aim of this exploratory case-series study was to comprehensively evaluate the clinical, hormonal, ultrasonographic, morphological, morphometric, immunohistochemical, and molecular cytogenetic characteristics of the ovaries in adolescents with mosaic TS and spontaneous pubertal development.

Five adolescents with mosaic TS underwent assessment of ovarian reserve markers and ovarian tissue cryopreservation. Follicle density (FD), expression of oocyte-specific markers (GDF9, BMP15, and CD117), and X chromosome mosaicism in 2-6 oocytes, 50-300 granulosa cells (GCs), and 50 ovarian stromal cells per participant were evaluated.

Despite ongoing puberty and normal gonadotropin levels, reduced serum anti-Müllerian hormone (AMH) and inhibin B concentrations were observed in some participants. A normal X chromosome complement was identified in all analyzed oocytes. Ovarian stromal cells were predominantly monosomic for the X chromosome, whereas GCs demonstrated substantial intra- and inter-individual variability in X chromosome mosaicism. No clear relationship was observed between X chromosome mosaicism in peripheral blood lymphocytes and ovarian tissue. Age-appropriate FD was observed only in participants whose follicles contained more than 60% non-monosomic GCs (XX or XXX).

The findings suggest that ovarian function in adolescents with mosaic TS may be associated not only with the chromosomal status of oocytes but also with that of GCs. Peripheral blood karyotype did not reliably reflect ovarian tissue mosaicism in this exploratory series, highlighting the importance of comprehensive evaluation of ovarian reserve markers when counseling patients with TS regarding fertility preservation.