Peek Ron, van der Coelen Sanne, Dolmans Marie-Madeleine
Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands.
Gynaecology Research Unit, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.
Mol Hum Reprod. 2024 Dec 11;30(12). doi: 10.1093/molehr/gaae043.
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.
在嵌合型特纳综合征患者中，卵巢体细胞（颗粒细胞和基质细胞）呈现高水平的非整倍体，核型为45,X，这可能影响卵巢中的基因表达并导致其生育力下降。当前研究的目的是探讨卵巢体细胞非整倍体对嵌合型（45,X/46,XX）特纳综合征患者卵巢皮质基质细胞和小卵泡基因表达的影响。为此，通过腹腔镜手术从8名嵌合型特纳综合征患者（年龄5 - 19岁）和8名对照者（年龄6 - 18岁）获取卵巢皮质组织。将组织进行分离以获得纯化的卵泡和基质细胞。部分纯化组分用于通过间期荧光原位杂交确定特纳综合征患者卵巢细胞的X染色体含量，而其余部分用于将这些细胞的基因表达谱与对照者进行比较。结果表明，与对照者相比，特纳综合征患者皮质基质细胞中高水平的45,X单倍体对基因表达、卵巢大体形态或皮质组织学外观均无影响。对主要含有45,X颗粒细胞的特纳综合征患者纯化小卵泡进行基因表达分析，发现11个基因表达异常。其中，与对照卵泡相比，6个基因上调（CD24、TLR1、EPHA²、PLXND¹、ST6GALNAC⁵和NOX⁴），5个基因（CRYAB、DLX¹、PCYT²、TNFRSF⁸和CA¹²）下调。有趣的是，这些小卵泡中过表达的基因均与卵泡发育的更高级阶段相关。这种卵泡中异常基因表达对特纳综合征患者的影响仍有待研究，但可能会影响生育力。
