Fertility Clinic, Zealand University Hospital, Lykkebækvej 14, 4600 Køge, Denmark.
Laboratory of Reproductive Biology, University Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
Mol Hum Reprod. 2020 Apr 24;26(4):256-268. doi: 10.1093/molehr/gaaa013.
Changes in concentrations of intra-follicular hormones during ovulation are important for final oocyte maturation and endometrial priming to ensure reproductive success. As no human studies have investigated these changes in detail, our objective was to describe the dynamics of major follicular fluid (FF) hormones and transcription of steroidogenic enzymes and steroid receptors in human granulosa cells (GCs) during ovulation. We conducted a prospective cohort study at a public fertility clinic in 2016-2018. Fifty women undergoing ovarian stimulation for fertility treatment were included. From each woman, FF and GCs were collected by transvaginal ultrasound-guided follicle puncture of one follicle at two specific time points during ovulation, and the study covered a total of five time points: before ovulation induction (OI), 12, 17, 32 and 36 h after OI. Follicular fluid concentrations of oestradiol, progesterone, androstenedione, testosterone, 17-hydroxyprogesterone, anti-Mullerian hormone, inhibin A and inhibin B were measured using ELISA assays, and a statistical mixed model was used to analyse differences in hormone levels between time points. Gene expression of 33 steroidogenic enzymes and six hormone receptors in GCs across ovulation were assessed by microarray analysis, and selected genes were validated by quantitative reverse transcription PCR. We found that concentrations of oestradiol, testosterone, progesterone, AMH, inhibin A and inhibin B (P < 0.001) and gene expression of 12 steroidogenic enzymes and five receptors (false discovery rate < 0.0001) changed significantly during ovulation. Furthermore, we found parallel changes in plasma hormones. The substantial changes in follicular hormone production during ovulation highlight their importance for reproductive success.
在排卵过程中，卵泡内激素浓度的变化对于卵母细胞的最终成熟和子宫内膜的启动至关重要，以确保生殖成功。由于没有人类研究详细研究过这些变化，我们的目的是描述人类卵泡液（FF）中主要激素的动力学以及排卵过程中颗粒细胞（GC）中类固醇生成酶和类固醇受体的转录。我们于 2016 年至 2018 年在一家公立生育诊所进行了一项前瞻性队列研究。共纳入 50 名接受卵巢刺激以进行生育治疗的女性。从每位女性中，通过经阴道超声引导的卵泡穿刺从一个卵泡中在排卵期间的两个特定时间点采集 FF 和 GC，该研究共涵盖五个时间点：排卵诱导前（OI），OI 后 12、17、32 和 36 小时。使用 ELISA 测定法测定卵泡液中雌二醇、孕酮、雄烯二酮、睾酮、17-羟孕酮、抗苗勒管激素、抑制素 A 和抑制素 B 的浓度，并使用统计混合模型分析各时间点激素水平的差异。通过微阵列分析评估排卵过程中 GC 中 33 种类固醇生成酶和 6 种激素受体的基因表达，并通过定量逆转录 PCR 验证选定基因。我们发现，雌二醇、睾酮、孕酮、AMH、抑制素 A 和抑制素 B 的浓度（P <0.001）以及 12 种类固醇生成酶和 5 种受体的基因表达（错误发现率<0.0001）在排卵过程中均发生了显著变化。此外，我们发现血浆激素也发生了平行变化。在排卵过程中，卵泡激素产生的巨大变化强调了它们对生殖成功的重要性。
