期刊
FRONTIERS IN NEUROSCIENCE
卷 15, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2021.780698
关键词
carbon black nanoparticles; pituitary; gonadotropin; GnRH; cAMP; PKA pathway; endocrine disruption
资金
- Agence nationale de la securite sanitaire de l'alimentation, de l'environnement et du travail (ANSES, Nanovhyp project)
- Universite de Paris, CNRS
- INSERM
- ANSES postdoctoral fellowship
The study found that exposure to carbon black nanoparticles does not disrupt estrous cyclicity in female mice, but increases FSH levels. Treating anterior pituitary or gonadotrope cells with CB NPs dose-dependently up-regulates FSH gene expression without affecting LH. The nanoparticles are internalized by cells and activate the cAMP/PKA pathway, leading to an imbalance in gonadotropins.
Toxic effects of nanoparticles on female reproductive health have been documented but the underlying mechanisms still need to be clarified. Here, we investigated the effect of carbon black nanoparticles (CB NPs) on the pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which are key regulators of gonadal gametogenesis and steroidogenesis. To that purpose, we subjected adult female mice to a weekly non-surgical intratracheal administration of CB NPs at an occupationally relevant dose over 4 weeks. We also analyzed the effects of CB NPs in vitro, using both primary cultures of pituitary cells and the L beta T2 gonadotrope cell line. We report here that exposure to CB NPs does not disrupt estrous cyclicity but increases both circulating FSH levels and pituitary FSH beta-subunit gene (Fshb) expression in female mice without altering circulating LH levels. Similarly, treatment of anterior pituitary or gonadotrope L beta T2 cells with increasing concentrations of CB NPs dose-dependently up-regulates FSH but not LH gene expression or release. Moreover, CB NPs enhance the stimulatory effect of GnRH on Fshb expression in L beta T2 cells without interfering with LH regulation. We provide evidence that CB NPs are internalized by L beta T2 cells and rapidly activate the cAMP/PKA pathway. We further show that pharmacological inhibition of PKA significantly attenuates the stimulatory effect of CB NPs on Fshb expression. Altogether, our study demonstrates that exposure to CB NPs alters FSH but not LH expression and may thus lead to gonadotropin imbalance.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据