Laboratory of Reproductive Biology, The Juliane Marie Centre for Women, Children and Reproduction, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
J Assist Reprod Genet. 2021 Jun;38(6):1341-1348. doi: 10.1007/s10815-021-02244-8. Epub 2021 May 28.
To investigate the effect of different FSH concentrations on human oocyte maturation in vitro and its impact on gene expression of key factors in the surrounding cumulus cells.
The study included 32 patients who underwent unilateral oophorectomy for ovarian tissue cryopreservation (OTC) (aged 28 years on average). Immature oocytes were collected from surplus medulla tissue. A total of 587 immature oocytes were divided into three categories according to the size of the cumulus mass: large (L-COCs), small (S-COCs), and naked oocytes (NOs), and submitted to 44-h IVM with one of the following concentrations of recombinant FSH: 0 IU/L, 20 IU/L, 40 IU/L, 70 IU/L, or 250 IU/L. After IVM, oocyte nuclear maturation stage and diameter were recorded. The relative gene expression of FSHR, LHCGR, and CYP19A1 in cumulus cells before (day 0; D0) and after IVM were evaluated.
Addition of 70 or 250 IU/L FSH to the IVM medium improved oocyte nuclear maturation compared to 0, 20, and 40 IU/L FSH by upregulating LHCGR and downregulating FSHR in the cumulus cells.
FSH improved oocyte nuclear maturation at concentrations above 70 IU/L suggesting a threshold for FSH during IVM of ex vivo collected human oocytes from small antral follicles. Moreover, current results for the first time highlight that FSH function in vitro is mediated via cumulus cells by downregulating FSHR and upregulating LHCGR, which was also observed when the immature oocytes progressed in meiosis from the GV to the MII stage.
研究不同 FSH 浓度对体外人卵母细胞成熟的影响及其对周围卵丘细胞关键因子基因表达的影响。
本研究纳入 32 例行单侧卵巢组织冷冻保存（OTC）的卵巢组织切除术患者（平均年龄 28 岁）。从剩余的髓质组织中收集未成熟卵母细胞。根据卵丘质量的大小，将 587 个未成熟卵母细胞分为三类：大（L-COCs）、小（S-COCs）和裸卵（NOs），并在以下浓度的重组 FSH 中进行 44 小时 IVM：0 IU/L、20 IU/L、40 IU/L、70 IU/L 或 250 IU/L。IVM 后，记录卵母细胞核成熟阶段和直径。评估 IVM 前后卵丘细胞中 FSHR、LHCGR 和 CYP19A1 的相对基因表达。
与 0、20 和 40 IU/L FSH 相比，添加 70 或 250 IU/L FSH 可上调 LHCGR 并下调卵丘细胞中的 FSHR，从而改善卵母细胞核成熟。
FSH 在高于 70 IU/L 的浓度下可改善卵母细胞核成熟，提示在体外从小窦卵泡中收集的人类卵母细胞进行 IVM 时存在 FSH 的阈值。此外，目前的结果首次强调，FSH 在体外的功能是通过下调 FSHR 和上调 LHCGR 来介导的，这在未成熟卵母细胞从 GV 期进入 MII 期的减数分裂过程中也观察到。
