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人颗粒细胞中的多环芳烃:首次在体内发现及其与体重指数的正相关和对体外卵巢细胞类固醇生成的调节作用

Polycyclic aromatic hydrocarbons in human granulosa cells: first in vivo presence and positive correlation with body mass index and in vitro ovarian cell steroidogenesis regulation.

作者信息

Kurowska Patrycja, Berthet Lucille, Ramé Christelle, Węgiel Małgorzata, Maślanka Anna, Guérif Fabrice, Froment Pascal, Rak Agnieszka, Dupont Joelle

机构信息

Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, Gronostajowa 9 Street, Krakow 30-387, Poland.

INRAE UMR 85 Physiologie de la Reproduction et des Comportements, Nouzilly 37380, France.

出版信息

Environ Toxicol Pharmacol. 2025 Jan;113:104611. doi: 10.1016/j.etap.2024.104611. Epub 2024 Dec 16.

Abstract

Polycyclic Aromatic Hydrocarbons (PAHs) exposure leads to disorders reported in female infertility patients. Our hypothesis is that PAHs accumulate in granulosa cells (Gc) according to body mass index (BMI) and directly affects its functions. All 16 high-priority PAHs were in human FF, Gc and blood plasma with the highest concentration in Gc (GC-MS/MS). Their highest concentration was in obese Gc, except for acenaphthene and acenaphthylene, and positively correlated with BMI. In FF, we noted only positive correlation between naphthalene and BMI, whereas in blood plasma positive correlation between naphthalene, acenaphthene, pyrene and BMI. Phenanthrene and naphthalene but not fluoranthene inhibited totally steroidogenesis (ELISA), CYP19A1 mRNA expression (real-time PCR) and increased oxidative stress index and catalase expression in Gc independently on BMI. While all studied PAHs decreased Gc proliferation (BrdU assay) and viability (Cell Count kit-8 assay). Thus, Gc PAHs concentrations are positively correlated with BMI and alter ovarian functions.

摘要

多环芳烃(PAHs)暴露会导致女性不孕症患者出现相关病症。我们的假设是,PAHs会根据体重指数(BMI)在颗粒细胞(Gc)中蓄积,并直接影响其功能。通过气相色谱-串联质谱法(GC-MS/MS)检测发现,在人卵泡液(FF)、颗粒细胞和血浆中均存在所有16种高优先级PAHs,其中颗粒细胞中的浓度最高。除苊和苊烯外,其在肥胖颗粒细胞中的浓度最高,且与BMI呈正相关。在卵泡液中,我们仅发现萘与BMI呈正相关,而在血浆中,萘、苊、芘与BMI呈正相关。菲和萘而非荧蒽可完全抑制颗粒细胞的类固醇生成(酶联免疫吸附测定法)、CYP19A1 mRNA表达(实时聚合酶链反应),并独立于BMI增加颗粒细胞的氧化应激指数和过氧化氢酶表达。而所有研究的PAHs均会降低颗粒细胞增殖(溴脱氧尿苷检测法)和活力(细胞计数试剂盒-8检测法)。因此,颗粒细胞中PAHs浓度与BMI呈正相关,并会改变卵巢功能。

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