INFLAMMATION IN PROGESTERONE RECEPTOR B KNOCKOUT (PRBKO) MICE ALTERS ALDO-KETOREDUCTASE FAMILY 1 MEMBER C18 (Akr1c18) EXPRESSION IN THE OVARY

Objective: Progesterone signaling is critical for decidualization and blastocyst implantation, and specifically reduced progesterone receptor B (PR-B) expression has been associated with endometriosis and subfertility. Because Akr1c18 has been shown to contribute to progesterone metabolism, we evaluated whether inflammation alters ovarian Akr1c18 expression in progesterone receptor B knockout (PRBKO) versus wild type mice. Design: Experimental animal study Materials and Methods: Female CD-1 WT and PRBKO mice were mated with proven-fertile B6D2F1/J male mice. On embryonic day (ED) 0.5, females received intraperitoneal injection of lipopolysaccharide (LPS; 5 µg in 100 µL PBS) or vehicle control (100 µL PBS). Mice were sacrificed on ED 5.5 and uteri and ovaries were collected. Immunohistochemistry (IHC) was used to assess Akr1c18 expression. Positive detections per mm2 in primordial follicles, advanced follicles, and the corpus lutuem in the ovaries were compared between WT control, WT LPS, PRBKO control, and PRBKO LPS treatment for ED 5.5 using one-way ANOVA (or Kruskal- Wallis if nonparametric), with p < 0.05 considered significant. Results: In the ovary, the PRBKO primordial follicle at ED 5.5 (n=3 mice) expressed less Akr1c18 than the WT (n=6 mice) (3.3 vs. 12.8, p=0.04). The advanced follicle of the PRBKO mice at ED 5.5 had a decrease in Akr1c18 expression after LPS exposure (14 vs. 3, p=0.045). At ED 5.5, corpus luteum of PRBKO mice exposed to LPS had lower Akr1c18 vs. WT mice (6 mice) after LPS (2 vs. 13, p=0.017). No other ovarian comparisons were different. Conclusion: PRBKO mice demonstrated decreased ovarian Akr1c1 expression following inflammatory challenge with LPS compared to control. Our findings suggest PRB may play a role in progesterone regulation via expression of the progesterone-metabolizing Akr1c18, particularly in response to an inflammatory challenge. Support: Supported by a grant from the Cleveland Society of Obstetricians and Gynecologists.