Berberine improves ovulation and endometrial receptivity in polycystic ovary syndrome

Zhi Wang; Kexin Nie; Hao Su; Yueheng Tang; Hongzhan Wang; Xiaohu Xu; Hui Dong

doi:10.1016/j.phymed.2021.153654

Berberine improves ovulation and endometrial receptivity in polycystic ovary syndrome

Phytomedicine. 2021 Oct:91:153654. doi: 10.1016/j.phymed.2021.153654. Epub 2021 Jul 12.

Authors

Zhi Wang¹, Kexin Nie¹, Hao Su¹, Yueheng Tang¹, Hongzhan Wang¹, Xiaohu Xu², Hui Dong³

Affiliations

¹ Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: hermanxu@163.com.
³ Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: tjhdonghui@163.com.

PMID: 34333328
DOI: 10.1016/j.phymed.2021.153654

Abstract

Background: Polycystic ovary syndrome (PCOS) is a clinical syndrome with reproductive and endocrine disorders. Berberine is a monomer from Chinese herbs such as Coptis chinensis, whose effect on improving ovulation and endometrial receptivity of PCOS is uncertain.

Purpose: To evaluate the effect of berberine on improving PCOS and explore the mechanism.

Methods: The rat model of PCOS was induced by intraperitoneal injection of testosterone propionate. Then they was divided into model (Mod) group, low-dose of berberine (BL) group, high-dose of berberine (BH) group and metformin (Met) group as well as a control (Con) group was established. Ovary morphology, hormone level, glucolipid metabolism were measured. UID-mRNA-seq of ovary tissue was conducted to seek the mechanism of berberine on improving ovulation. Three biomarkers of endometrial receptivity were also examined in endometrium by immunohistochemistry.

Results: The number of cystic follicles was increased while the number of corpus luteum was decreased in the rats of Mod group. These changes could be reversed by high-dose of berberine intervention. Berberine could also decrease the levels of serum luteinizing hormone (LH) and total cholesterol (TC) in PCOS rats. Meanwhile, berberine improved the impairment of abnormal oral glucose tolerance without affecting fasting insulin level and Homeostasis model assessment-insulin resistance (HOMA-IR). Luteinizing hormone/ choriogonadotropin receptor (LHCGR) and cytochrome P450 Family 19 Subfamily A Member 1 (CYP19A1) were focused via RNA-seq of ovary. Protein expression in ovary and mRNA expression in granulosa cell of LHCGR and CYP19A1 were decreased in Mod group and rescued by the intervention of berberine. A decrease of endometrial thickness and an increase of integrin αvβ3 and lysophosphatidic acid receptor 3 (LPAR3) protein expression were observed in Mod group, which could be also reversed by berberbine.

Conclusions: Berberine could improve ovulation in PCOS and the mechanism might be associated with up-regulating LHCGR and CYP19A1. Berberine could also improve endometrial receptivity through down-regualting αvβ3 and LPAR3.

Keywords: Berberine; Endometrial receptivity; Ovulation; PCOS.

MeSH terms

Animals
Berberine* / pharmacology
Endometrium / drug effects
Female
Metformin
Ovulation / drug effects*
Polycystic Ovary Syndrome* / drug therapy
Rats

Substances

Berberine
Metformin