Preclinical Effect of Shaofu Zhuyu Decoction on Decidualization and the Expression of PR-β and HNRNPL in a Mouse Model of Endometriosis-Associated Infertility

Chen Zhang,1 Xinhui Sun,2,3 Conglu Sui,1 Ying Cao4,51Department of Gynecology, Beijing University of Chinese Medicine Affiliated Third Hospital, Beijing, People’s Republic of China; 2Department of Gynecology, The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 3Department of Gynecology, National Clinical Research Center for Chinese Medicine, Tianjin, People’s Republic of China; 4Department of Gynecology, Beijing Tongrentang Traditional Chinese Medicine Hospital, Beijing, People’s Republic of China; 5Department of Integrated Traditional Chinese and Western Clinical Medicine, College of Traditional Chinese Medicine, North China University of Science and Technology, Tangshan, Hebei, People’s Republic of ChinaCorrespondence: Conglu Sui, Email [email protected] Ying Cao, Email [email protected]: To investigate the effects of Shaofu Zhuyu Decoction on decidualization and the expression of progesterone receptor-β (PR-β) and heterogeneous nuclear ribonucleoprotein L (HNRNPL) in a mouse model of endometriosis.Methods: An endometriosis mouse model was established by allogeneic uterine transplantation. Sixty recipient mice were randomized into model (Model), medium-dose (SF-M), and high-dose (SF-H) Shaofu Zhuyu Decoction groups (n=20 each), with 20 normal mice as controls (NC). Doses (9.403 and 18.806 g·kg− 1·day− 1) were derived from clinical equivalence via body surface area conversion. After 4 weeks of gavage, females were mated. Mice were sacrificed on gestational days (GD) 4.5, 5.5, and 7.5 (n=6-7/group/time point). Pregnancy rates, implantation sites, and histology were assessed. IGFBP1, PRL, PR-β, and HNRNPL protein expression were detected by Western blotting.Results: Compared with NC, the Model group showed a lower pregnancy rate (66.67% vs 100%) although this difference was not statistically significant (p > 0.05), however, it exhibited significantly reduced implantation numbers (median 7 vs 9, p < 0.05). IGFBP1 was decreased (p < 0.01), while PRL was increased (p < 0.01). PR-β was lower at GD4.5 but higher at GD5.5 and GD7.5 versus NC (p < 0.05), whereas HNRNPL was consistently lower in the Model group (p < 0.01). Both SF-M and SF-H significantly increased implantation numbers versus Model (p < 0.05). SF-H also upregulated IGFBP1 (p < 0.01), reduced PRL (p < 0.05), normalized the abnormal PR-β temporal pattern, and increased HNRNPL (p < 0.05).Conclusion: Shaofu Zhuyu Decoction, particularly at the high dose, improved impaired decidualization in endometriosis model mice, potentially via regulation of PR-β and HNRNPL. These preclinical findings support further investigation of this formula for endometriosis-associated infertility. However, as an observational protein-level study without mechanistic validation, the results should be considered exploratory.Keywords: Shaofu Zhuyu Decoction, endometriosis, decidualization, progesterone receptor-β, heterogeneous nuclear ribonucleoprotein L