Looney Rachel J, Roberts Mackenzie, Markovetz Matthew, Godiah Rachelle, Yao Shan, Golgotiu Kirsti, Wei Shuhao, Cellucci Chris, Han Leo
Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, OR, USA.
Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, USA.
Biol Reprod. 2025 May 9. doi: 10.1093/biolre/ioaf103.
Cervical mucus changes throughout the menstrual cycle in response to hormonal fluctuations, regulating access of sperm and pathogens to the reproductive tract. CFTR is an anion channel that plays a critical role in mediating epithelial mucus secretions. Primary endocervical cells obtained from rhesus macaques Macaca mulatta were cultured using conditional reprogramming and treated with vehicle controls or CFTR inhibitors. In order to measure changes in hydration and viscosity of secreted mucus, we adapted two airway mucus assays, airway surface liquid and particle-tracking microrheology, for our endocervical culture system. Endocervical cells treated with CFTR inhibitors demonstrated dehydrated, thicker mucus secretions compared to controls in both assay outputs. Our studies suggest that CFTR may be an important mediator of fertility changes and provide experimental evidence for the infertility phenotype seen in women with cystic fibrosis. Additionally, assays developed in these studies provide new endpoints for assessing cervical mucus changes in vitro.
宫颈黏液在整个月经周期中会随着激素波动而变化，从而调节精子和病原体进入生殖道的机会。囊性纤维化跨膜传导调节因子（CFTR）是一种阴离子通道，在介导上皮黏液分泌中起关键作用。使用条件重编程培养从恒河猴（猕猴）获得的原代宫颈内膜细胞，并用溶剂对照或CFTR抑制剂进行处理。为了测量分泌黏液的水合作用和黏度变化，我们将两种气道黏液检测方法，即气道表面液体检测和颗粒追踪微观流变学检测，应用于我们的宫颈内膜培养系统。在两种检测结果中，与对照相比，用CFTR抑制剂处理的宫颈内膜细胞表现出脱水且更黏稠的黏液分泌。我们的研究表明，CFTR可能是生育能力变化的重要调节因子，并为囊性纤维化女性中出现的不孕表型提供了实验证据。此外，这些研究中开发的检测方法为体外评估宫颈黏液变化提供了新的指标。
