The Plasminogen Activator System, Glucocorticoid, and Mineralocorticoid Receptors in the Primate Endometrium During Artificial Menstrual Cycles

As a key mechanism in fibrinolysis and tissue remodeling, the plasminogen activator system has been suggested in the process of endometrial shedding and tissue remodeling. Previous studies have explored the role of estrogen, progesterone, and androgen receptors as well as elements of the renin–angiotensin–aldosterone system in shaping the morphology of the endometrium. This study investigates the distribution and concentrations of the mineralocorticoid receptor, glucocorticoid receptor, tissue plasminogen activator, urokinase plasminogen activator, and plasminogen activator inhibitor-1 within the endometrial stroma, glandular, and endothelial cells of the primate endometrium during artificial menstrual cycles. Our immunohistochemistry quantification shows mineralocorticoid and glucocorticoid receptors are ubiquitously distributed within the macaque endometrium with their patterns of expression following similar fluctuations to urokinase and tissue plasminogen activators particularly within the endometrial vasculature. These proteins are present in endometrial vasculature in high levels during the proliferative phase, decreasing levels during the secretory phase followed by rising levels in the menstrual phase. These similarities could suggest overlapping pathways and interactions between the plasminogen activator system and the steroid receptors within the endometrium. Given the anti-inflammatory properties of glucocorticoids and the role of plasminogen activators in endometrial breakdown, the glucocorticoid receptor may be contributing to stabilizing the endometrium by regulating plasminogen activators during the proliferative phase and menstruation. Furthermore, given the anti-mineralocorticoid properties of certain anti-androgenic progestins and their reduced unscheduled uterine bleeding patterns, the mineralocorticoid receptor may be involved in unscheduled endometrial bleeding. Similar content being viewed by others

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Author information Authors and Affiliations Contributions The authors contributed to this work as follows: ED performed immunohistochemistry analysis, collected data, and wrote the manuscript; RS performed immunohistochemistry analysis and collected data; NC performed immunohistochemistry and immunofluorescent staining on slides and performed statistical analysis; ODS carried out the primate artificial menstrual cycles and provided the macaque hysterectomy samples; DFA conceived and supervised the study, and helped with preparation of the manuscript. Corresponding author Ethics declarations Ethics Approval Animal husbandry was provided by the ONPRC Department of Comparative Medicine and animal use was reviewed and approved by the ONPRC Institutional Animal Care and Use Committee. Conflict of Interest The authors declare no competing of interest. Rights and permissions About this article Cite this article Demirel, E., Sabouni, R., Chandra, N. et al. The Plasminogen Activator System, Glucocorticoid, and Mineralocorticoid Receptors in the Primate Endometrium During Artificial Menstrual Cycles. Reprod. Sci. 29, 1001–1019 (2022). https://doi.org/10.1007/s43032-021-00797-8 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-021-00797-8