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体外受精女性卵泡液中脂质及其代谢产物的浓度与卵巢内促性腺激素刺激的雄激素生成有关。

Follicular fluid concentrations of lipids and their metabolites are associated with intraovarian gonadotropin-stimulated androgen production in women undergoing in vitro fertilization.

作者信息

Gervais A, Battista M-C, Carranza-Mamane B, Lavoie H B, Baillargeon J-P

机构信息

Division of Endocrinology (A.G., M.-C.B., J.-P.B.), Department of Medicine, and Department of Obstetrics and Gynecology (B.C.-M.), Université de Sherbrooke, and Centre de Recherche Clinique Étienne-LeBel (B.C.-M., J.-P.B.), Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4; and PROCREA Cliniques (B.C.-M.), Mt Royal, Québec, Canada H3P 2W3.

出版信息

J Clin Endocrinol Metab. 2015 May;100(5):1845-54. doi: 10.1210/jc.2014-3649. Epub 2015 Feb 19.

Abstract

CONTEXT

Although growing evidence points toward a role of lipotoxicity in the development of hyperandrogenesis, the main feature of polycystic ovary syndrome, few studies directly assessed this association in vivo in humans, and none targeted the ovarian milieu.

OBJECTIVE

The main objective of this study was to correlate follicular fluid (FF) T levels with lipids, lipid metabolites, and inflammation markers.

DESIGN

This was a cross-sectional study.

SETTING

Recruitment was performed in two fertility clinics at one private and one academic center.

PARTICIPANTS

Eighty women requiring in vitro fertilization were recruited during one of their scheduled visit at the fertility clinic. All women aged between 18 and 40 years with a body mass index between 18 and 40 kg/m(2) were invited to participate.

INTERVENTION(S): There were no interventions.

MAIN OUTCOME MEASURE(S): At the time of oocyte aspiration, FF was collected and analyzed for total T, lipids [nonesterified fatty acids (NEFAs) plus triglycerides], NEFA metabolites (acylcarnitines; markers of ineffective NEFAs β-oxidation), and inflammatory marker composition. The hypothesis being tested was formulated before the data collection.

RESULTS

FF T levels were significantly correlated with FF levels of lipids (r = 0.381, P = .001; independently of IL-6), acylcarnitines (r ≥ 0.255, all P = .008; not independently of lipids), and IL-6 (r = 0.300, P = .009, independently of lipids). Additionally, FF lipid levels were significantly and strongly correlated with acylcarnitines (r ≥ 0.594; all P < .001).

CONCLUSIONS

These results suggest that ovarian androgen production is related to intraovarian exposure to lipids, independently of inflammation and mainly through ineffective NEFA β-oxidation (as shown by higher acylcarnitine levels). Inflammation is also associated with intraovarian androgenesis, independently of lipids.

摘要

背景

尽管越来越多的证据表明脂毒性在高雄激素血症(多囊卵巢综合征的主要特征)的发生发展中起作用,但很少有研究在人体中直接评估这种体内关联,且尚无研究针对卵巢微环境。

目的

本研究的主要目的是将卵泡液(FF)睾酮水平与脂质、脂质代谢产物及炎症标志物进行关联分析。

设计

这是一项横断面研究。

地点

在一家私立和一家学术中心的两家生育诊所进行招募。

参与者

在生育诊所的一次预定就诊期间,招募了80名需要体外受精的女性。邀请了所有年龄在18至40岁、体重指数在18至40kg/m²之间的女性参与。

干预措施

无干预措施。

主要观察指标

在卵母细胞抽吸时,收集FF并分析总睾酮、脂质(非酯化脂肪酸[NEFA]加甘油三酯)、NEFA代谢产物(酰基肉碱;无效NEFAβ氧化的标志物)及炎症标志物组成。所检验的假设在数据收集前已制定。

结果

FF睾酮水平与FF脂质水平(r = 0.381,P = 0.001;独立于白细胞介素-6[IL-6])、酰基肉碱水平(r≥0.255,所有P = 0.008;不独立于脂质)及IL-6水平(r = 0.300,P = 0.009,独立于脂质)显著相关。此外,FF脂质水平与酰基肉碱显著且强烈相关(r≥0.594;所有P < 0.001)。

结论

这些结果表明,卵巢雄激素生成与卵巢内脂质暴露有关,独立于炎症,主要通过无效的NEFAβ氧化(如较高的酰基肉碱水平所示)。炎症也与卵巢内雄激素生成有关,独立于脂质。

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