The effect of growth hormone on the metabolome of follicular fluid in patients with diminished ovarian reserve.

The effect of growth hormone on the metabolome of follicular fluid in patients with diminished ovarian reserve.
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DOI:
10.1186/s12958-023-01073-x
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发表时间:
2023-02-27
期刊:
Reproductive biology and endocrinology : RB&E
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越来越多的证据表明,在卵巢储备功能下降(DOR)患者的控制性卵巢刺激(COS)期间,生长激素(GH)联合治疗可提高卵巢反应性和卵母细胞质量。卵泡液(FF)的组成在卵母细胞的发育过程中起着重要的作用,并反映了卵母细胞和卵泡微环境之间的沟通。然而,GH对FF代谢组的影响仍不清楚。这项前瞻性观察性研究招募了接受体外受精(IVF)周期的DOR患者,采用最小刺激方案治疗COS。通过倾向评分匹配,将接受GH联合治疗的每例患者与未接受GH联合治疗的患者进行匹配。分离卵母细胞后收集FF,并通过气相色谱-质谱(GC-MS)代谢组学进行分析。Pearson相关分析用于评价获得的卵母细胞数量与差异代谢物水平之间的关系。KEGG数据库用于将差异代谢物映射到各种代谢途径。通过GC-MS代谢组学鉴定了134种FF代谢物。24种代谢产物,包括谷胱甘肽、衣康酸和S-腺苷甲硫氨酸(SAM),在GH组和对照组之间显示出显著差异(p值< 0.05,q值< 0.1)。此外,GH组中获得的卵母细胞数量显著高于对照组(3 vs 2,p = 0.04),并与5种差异代谢产物的水平相关。其中,抗氧化代谢产物衣康酸的水平通过GH给药上调,而SAM水平下调。COS期间与GH联合治疗可能通过改变DOR患者的FF代谢产物谱来改善卵母细胞发育。然而,考虑到SAM的下调,基因组印迹的调节,印迹干扰的潜在风险不应被忽视。在线版本包含补充材料,可通过10.1186/s12958-023-01073-x获得。
Increasing evidence supports that the co-treatment with growth hormone (GH) enhances ovarian response and oocyte quality during controlled ovarian stimulation (COS) in patients with diminished ovarian reserve (DOR). The composition of follicular fluid (FF) plays an essential role in oocyte development and mirrors the communication occurring between the oocyte and follicular microenvironment. However, the effect of GH on the FF metabolome remains unclear. This prospective observational study recruited DOR patients undergoing in vitro fertilization (IVF) cycles with minimal stimulation protocol for COS. Each patient receiving GH co-treatment was matched to a patient without GH co-treatment by propensity score matching. The FF was collected after isolating oocytes and assayed by gas chromatograph-mass spectrometry (GC-MS) metabolomics. The Pearson correlation was performed to evaluate the relationship between the number of oocytes retrieved and the levels of differential metabolites. The KEGG database was used to map differential metabolites onto various metabolic pathways. One hundred thirty-four FF metabolites were identified by GC-MS metabolomics. Twenty-four metabolites, including glutathione, itaconic acid and S-adenosylmethionin (SAM) showed significant differences between the GH and control groups (p-value < 0.05 and q-value < 0.1). In addition, the number of oocytes retrieved was significantly higher in the GH group compared to the control group (3 vs 2, p = 0.04) and correlated with the levels of five differential metabolites. Among them, the levels of antioxidant metabolite itaconic acid were upregulated by GH administration, while SAM levels were downregulated. The co-treatment with GH during COS may improve oocyte development by altering FF metabolite profiles in DOR patients. However, given the downregulation of SAM, a regulator of genomic imprinting, the potential risk of imprinting disturbances should not be neglected. The online version contains supplementary material available at 10.1186/s12958-023-01073-x.
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