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Updated: May 4, 2026
In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes
Published on: August 13, 2012
In vitro inhibition of the CFTR ion channel in the Macaca mulatta cervix thickens cervical mucus†
Rachel J Looney1, Mackenzie Roberts1, Matthew Markovetz2
1Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, 505 NW 185th Ave, Beaverton, OR 97006, USA.
Abstract:
Cervical mucus changes throughout the menstrual cycle in response to hormonal fluctuations, regulating access of sperm and pathogens to the reproductive tract. Cystic Fibrosis Transmembrane Conductance Regulator (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.
Insights
Cystic fibrosis transmembrane conductance regulator (CFTR) inhibitors thicken cervical mucus, potentially explaining infertility in cystic fibrosis patients and offering new ways to study fertility.
Area of Science:
- Reproductive biology
- Epithelial physiology
- Ion channel function
Background:
- Cervical mucus composition changes during the menstrual cycle, influencing reproductive tract access.
- The cystic fibrosis transmembrane conductance regulator (CFTR) is crucial for epithelial mucus secretion.
- CFTR dysfunction is linked to various health issues, including potential fertility impacts.
Purpose of the Study:
- To investigate the role of CFTR in regulating cervical mucus hydration and viscosity.
- To adapt existing airway mucus assays for assessing endocervical mucus properties.
- To explore the link between CFTR activity and infertility, particularly in cystic fibrosis.
Main Methods:
- Primary endocervical cells from rhesus macaques were cultured using conditional reprogramming.
- Cells were treated with either vehicle controls or CFTR inhibitors.
- Adapted airway surface liquid and particle-tracking microrheology assays were used to measure mucus hydration and viscosity.
Main Results:
- CFTR inhibition led to significantly dehydrated and thicker cervical mucus secretions compared to controls.
- Both adapted assays consistently showed increased mucus viscosity and dehydration upon CFTR inhibition.
- The results demonstrate CFTR's role in maintaining normal cervical mucus properties.
Conclusions:
- CFTR is a key mediator of cervical mucus hydration and viscosity.
- Inhibition of CFTR leads to mucus changes consistent with impaired fertility.
- These findings provide experimental support for the infertility observed in women with cystic fibrosis and introduce novel in vitro assays for cervical mucus research.
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