Nicotinic acetylcholine receptors (nAChR) are increased in the pre-eclamptic placenta

Abstract

Objective: The role of the nicotinic acetylcholine receptors (nAChR) in pre-eclampsia is unknown. Given that ACh levels are affected in pre-eclampsia, it has been suggested that compensatory changes in nAChR expression may ensue. This study aimed to determine the effects of pre-eclampsia on the mRNA and protein expression of 12 mammalian nAChR subunits. Methods: Placentas were collected from healthy term pregnancies (n = 8) and pregnancies complicated by pre-eclampsia (n = 7), both being non-cigarette smoke exposed to rule out any role of nicotine. Using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR), 12 subunits (α2, α3, α4, α5, α6, α7, α9, β1, β2, β4, δ, and γ) were able to be studied at the mRNA level, while at the protein level using Western blotting, nine subunits (α2, α3, α4, α5, α7, α9, β1, β2, and γ) were studied. Results: At the mRNA level, pre-eclamptic placentas showed an increase in α2 (p = 0.003), α9 (p < 0.001), β1 (p = 0.03) and β2 (p = 0.02) subunit expression, while at the protein level, α7 (p = 0.004), α9 (p = 0.02), and δ (p = 0.003) subunits were increased compared to controls. Conclusion: Certain nAChR subunits are increased in the pre-eclamptic placenta. Given the absence of cigarette smoking, the changes in expression are hypothesised to be due to the hypoxic environment resulting from the pathophysiology of pre-eclampsia, which subsequently affects endogenous ACh levels, yielding compensatory increases in α2, α7, α9, β1, β2, and δ nAChR subunits.

• ACh
• Blood pressure
• Hypoxia
• mRNA
• Nicotine
• Protein.

Acknowledgements

We thank Ms. Jane Tooher and Mrs. Annette Robertson for women recruitment to the study and placenta and blood collection. We acknowledge Dr. Donna Lai (Core Facilities Manager, Bosch Institute, The University of Sydney) for her support and assistance with troubleshooting the qPCR protocol.

Declaration of interest

Research was funded by PEARLS. There are no conflict of interest to declare.