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337 Acute Inflammation is Associated with Reduced Basal Decidua Progesterone Receptor Density in Spontaneous Preterm Birth

American Journal of Obstetrics and Gynecology(2024)

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Abstract
A functional progesterone withdrawal has been thought to contribute to the pathophysiology of preterm birth (PTB), a process potentially mediated in part by alterations in the progesterone receptor (e.g. isoform abundance, tissue distribution, quantity). We sought to understand the relationship between density of progesterone receptor in the decidua and placental pathology patterns. This is a retrospective cohort study leveraging a prior null result case-control study of 40 patients with spontaneous PTB < 37 weeks. The exposure of placental pathology was evaluated as absence/ presence of each of the major recognized patterns of placental injury including acute inflammation, chronic inflammation, maternal vascular malperfusion, and fetal vascular malperfusion. Slides containing basal decidua were stained for progesterone receptor (mouse monoclonal anti-human progesterone receptor antibody Clone PgR 1294, diluted 1:50), which stains for both PR-A and PR-B. 10 representative images were obtained for each sample and QuPath was utilized to determine the outcome of % positive stained cells for progesterone receptor. The average percentage of positive cells across the representative images was compared by t-tests for each pattern of placental injury. Average gestational age at index birth was 31 weeks per design of primary study. Among patients with acute inflammation (AI), there was a lower density of progesterone receptor staining (% positive cells 12.9 without AI vs 9.1 with AI, p= 0.03). There was no difference based on chronic inflammation, maternal vascular malperfusion, or fetal vascular malperfusion (Table 1). The presence of acute inflammation may be associated with lower density of progesterone receptor expression in the basal decidua. Further research is needed to investigate these findings in the context of spontaneous PTB and potential prevention of preterm birth. These findings may also be further explored in the setting of progesterone supplementation in pregnancies threatened by PTB.
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