Acute Placental Inflammation Is Associated with Reduced Progesterone Receptor Density in the Basal Decidua in Spontaneous Preterm Birth

Abstract

Objective A functional progesterone withdrawal has been thought to contribute to the pathophysiology of spontaneous preterm birth (PTB). The density of the progesterone receptor (PR) in gestational tissues could play a role in functional progesterone withdrawal. We sought to understand the relationship between placental pathology and the density of PR in the basal decidua in the setting of spontaneous preterm delivery.

Study Design This is a secondary analysis of a retrospective cohort study of 40 patients with spontaneous PTB < 37 weeks from a prior study at NorthShore University HealthSystem previously described. Placental pathology was categorized according to the Amsterdam criteria into acute inflammation (AI), chronic inflammation (CI), maternal vascular malperfusion (MVM), and fetal vascular malperfusion (FVM). Slides containing basal decidua were stained for PR. Ten distinct images were obtained from the basal plate of each placenta. The positive cell detection program in QuPath image analysis software was used to estimate the percentage of cells positive for PR (%PR + ). The mean %PR+ cells were calculated from the ten representative images and were correlated with patterns of placental injury using t-tests. Models were adjusted for gestational age at delivery.

Results The median gestational age at delivery was 32.5 weeks (interquartile range: 30.5, 34.1). There was a lower density of %PR+ cells among those with AI (12.9%PR+ without AI vs. 9.1%PR +  with AI, p = 0.03). There were no differences in the percent of %PR+ cells based on CI, MVM, or FVM. Models adjusted for gestational at delivery demonstrated persistent association with PR density and AI and no difference in the other pathologies.

Conclusion The presence of AI is associated with the lower density of PR expression in the basal decidua by quantitative immunohistochemical analysis. Further research is needed to investigate these findings in the context of spontaneous PTL and the prevention of PTB.

Key Points

• AI is associated with a lower density of PR expression.

• PR is expressed in the basal decidua in the placenta.

• Further research is needed to investigate findings in the context of PTB.

Keywords

placental pathology - preterm delivery - progesterone

Note

These findings were presented as a poster presentation at the Society for Maternal Fetal Medicine held in Washington DC in January 2024.

Publication History

Received: 01 January 2025

Accepted: 24 January 2025

Article published online:
24 February 2025

• References

• 1 Talati AN, Hackney DN, Mesiano S. Pathophysiology of preterm labor with intact membranes. Semin Perinatol 2017; 41 (07) 420-426
• 2 Merlino AA, Welsh TN, Tan H. et al. Nuclear progesterone receptors in the human pregnancy myometrium: evidence that parturition involves functional progesterone withdrawal mediated by increased expression of progesterone receptor-A. J Clin Endocrinol Metab 2007; 92 (05) 1927-1933
• 3 Nadeem L, Shynlova O, Matysiak-Zablocki E, Mesiano S, Dong X, Lye S. Molecular evidence of functional progesterone withdrawal in human myometrium. Nat Commun 2016; 7: 11565
• 4 Suresh S, Freedman A, Adams M, Hirsch E, Ernst LM. Placental histology for targeted risk assessment of recurrent spontaneous preterm birth. Am J Obstet Gynecol 2024; 230 (04) 452.e1-452.e11
• 5 Hassan SS, Romero R, Vidyadhari D. et al. PREGNANT Trial. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol 2011; 38 (01) 18-31