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Basic Science

Poster Session 3

(767) Differential Packaging of Nuclear and Membrane Progesterone Receptors in Myometrial and Decidual Cell Exosomes

Wednesday, February 14, 2024
8:30 AM – 10:00 AM  
Location: Prince George's Exhibit Hall CDE, Lower Atrium Level
Objective: Progesterone and its receptors (progesterone receptor membrane components-1/2 [PGRMC1/2] and nuclear progesterone receptors A/B [PRA/B]) play a crucial role in pregnancy maintenance by promoting decidualization, immunomodulation, uterine quiescence, and cervical integrity. The paracrine signaling functions they may provide when propagated via uterine cell-derived exosomes are unclear.

Study Design: Lysates of myometrial and decidual cells grown in a 2D culture were prepared, and extracellular vesicles (exosomes) were isolated from media using differential ultracentrifugation and size exclusion chromatography. Immunocytochemistry and western blots localized receptors within cells and exosomes. ZetaView determined exosome size, concentrations, and exosomal-enriched CD markers.

Results: Immunocytochemistry and western blot analysis of myometrial and decidual cell lysates confirmed the expression of both membrane (PGRMC1/PGRMC2) and genomic receptors (PRA/PRB). Myometrial and decidual cell-derived exosomes were around 110-130nm (Fig.1A;Fig.1C), concentrated within 109 -1010 per/ml (Fig.1A;Fig.1C), and expressed CD63 or CD9 (Fig.1B;Fig.1D). Myometrial exosomes predominantly expressed genomic receptors PRA/B (Fig.1B), while decidual exosomes expressed PGRMC1 (Fig.1D). These differences highlight the potential distinction in progesterone paracrine signaling and could be later used to target either cell type depending on the pathology.

Conclusion: We confirmed the expression of progesterone receptors and report their differential expressions in exosomes from myometrial and decidua cells. Given that a subset of pregnant women does not respond to progesterone treatment due to functional progesterone withdrawal, PR-containing exosomes could be utilized to deliver these receptors to gestational tissues during pregnancy. Potentially making them responsive to progesterone. Functional studies are still needed to understand the role of exosome-derived progesterone receptors.