Rapid Effects of Oestrogen on Intracellular Ca2+ in the Uterine Junctional Myometrium of Patients With and Without Adenomyosis in Different Phases of the Menstrual Cycle

We investigated the role of oestrogen receptor 1 (ESR1) in regulating the [Ca2+]i concentration in the junctional zone (JZ) and its effect on adenomyosis. JZ smooth muscle cells (JZSMCs) were isolated from 17 control and 24 adenomyotic uteri, and membrane proteins were extracted from the cells. In the control group, the levels of membrane ESR1 and [Ca2+]i in the proliferative phase were significantly greater than they were in the secretory phase. While no difference was detected between the two phases, ESR1 and [Ca2+]i levels in the adenomyosis group were significantly higher in the proliferative and secretory phases than they were in the control groups. Oestradiol induced a rapid increase in [Ca2+]i in the JZSMCs of both groups. When pretreated with the ESR1 antagonist ICI 182,780, the increase in [Ca2+]i was clearly reduced in both groups compared with the control, but the differences were not significant. Filtered E-6-BSA also induced [Ca2+]i, and its actions were similar to those of oestrogen. Removal of extracellular Ca2+ did not alter the effect of oestradiol, but the phospholipase C inhibitor U73122 (10 μM) and 2-aminoethoxydiphenyl borate (5 μM) significantly reduced the oestradiol-induced [Ca2+]i flux. Oestradiol was unable to induce a [Ca2+]i flux in thapsigargin-depleted cells; this result indicated that oestradiol mediates the [Ca2+]i flux in JZSMCs through ESR1, which activates the phospholipase C pathway. ESR1 levels were assessed by Western blotting. Changes in the [Ca2+]i concentration induced by oestrogen stimulation were analysed by immunofluorescence. The ΔFCa2+ was calculated as the difference between baseline and peak fluorescence response to stimulation. We found that the abnormal intracellular [Ca2+]i response to oestrogen could account for aberrant JZ peristalsis. Similar content being viewed by others Data Availability All analysis results are displayed on the results. For specific experimental data, please contact the corresponding author.

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Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Wang, S., Duan, H. & Li, B. Rapid Effects of Oestrogen on Intracellular Ca2+ in the Uterine Junctional Myometrium of Patients With and Without Adenomyosis in Different Phases of the Menstrual Cycle. Reprod. Sci. 27, 1992–2001 (2020). https://doi.org/10.1007/s43032-020-00218-2 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-020-00218-2