Oviduct Contractility in Non-pregnant Rats: Changes in Estrous Cycle and Effects of Estrogen and Progesterone Antagonist

Abstract This study aimed to systematically characterize oviduct contractility across the estrous cycle and to examine the regulatory roles of estradiol and progesterone, using receptor antagonists and molecular docking to explore both receptor-mediated and ion channel pathways. Female Wistar rats (n=48) were used for this purpose. Oviducts were collected during proestrus, estrus, metestrus, and diestrus, and spontaneous contractions were recorded using an isometric force transducer. Serum levels of estradiol, progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin were measured through enzyme-linked immunosorbent assay (ELISA). To understand hormonal regulation, tamoxifen (10 mg/kg) was administered during proestrus, and mifepristone (5 mg/kg) was administered during metestrus to assess hormonal regulation. Immunofluorescence (IF) study was performed to evaluate expression of the estrogen, progesterone, and glucocorticoid receptors (ER, PR, and GR). Molecular docking analysis assessed interactions of the antagonists with estrogen and progesterone receptors and ion channels. Oviduct contractility was observed noticeably highest during proestrus (high estradiol) and lowest in metestrus and diestrus phases (high progesterone). Tamoxifen significantly reduced contraction parameters (p<0.001) and estradiol levels, while mifepristone notably increased contraction force (p<0.01), elevated estradiol levels (p<0.001) and decreased the proportion of progesterone hormone. IF study indicated suppression of ER, PR, and GR expression following the treatment with mifepristone. Docking analysis revealed that tamoxifen interacted with potassium channels and ERβ, while mifepristone showed high affinity for PR, GR, and calcium channels. These findings highlight that oviduct contractility is dynamically regulated across the estrous cycle through both receptor-mediated and potential non-receptor and non-genomic pathways involving ion channels. Brief Statement The oviduct plays a crucial role in natural conception, yet it has been largely overlooked in recent reproductive research compared to the uterus due to the increasing reliance on assisted reproductive technologies. This study offers a comprehensive characterization of oviduct contractility across the estrous cycle, correlates it with endogenous hormone levels, and reveals new insights into the role of the glucocorticoid receptor in regulating oviduct contractions, highlighting both receptor-mediated and non-receptor pathways in the regulation of tubal motility.