Role and mechanism of alpa1-antitrypsin in polycystic ovary syndrome

Abstract

Objectives: To determine the relationships among alpha1-antitrypsin (A1AT), pro-inflammatory cytokines, neutrophil elastase (NE), interleukin (IL)- 1β, and IL-8 in cases with polycystic ovary syndrome (PCOS).

Methods: Female rats in the control group were fed and watered normally. Female rats in the PCOS group were given high-fat diets and letrozole (1% carboxymethyl cellulose' [CMC] solution) CMC by gavage at a dose of l mg/kg body weight daily for 23 days. The mRNA levels of A1AT and NE in rat ovaries were detected by performing real-time polymerase chain reaction (PCR) in the laboratory of Norman Bethune College of Medicine, Jilin University, China in 2017. All serum samples were collected from the Second Hospital of Jilin University from October 2021 to November 2021 for obesity concurrent with PCOS. Molecular docking of A1AT with NE, IL-8, and IL-1β was investigated using the Insight II software ZDOCK tool. This study was carried out at the Reproductive Center, The Second Hospital of Jilin University, Changchun, China from June 2021 to July 2022.

Results: The expression of the A1AT mRNA decreased in the ovary tissues of PCOS rats relative to that of healthy controls, while the expression of NE mRNA increased compared to that of normal controls. The serum A1AT expression in PCOS cases decreased considerably relative to their expression in normal controls. However, the expression of NE, IL-1β, and IL-8 increased significantly relative to their expression in the control (p<0.05 for all). The Insight II ZDOCK molecular docking simulations showed that A1AT has direct interaction sites for NE, IL-1β, and IL-8.

Conclusion: Alpha1-antitrypsin is closely associated with NE, IL-1β, and IL-8. Therefore, we speculate that A1AT might ameliorate PCOS symptoms by inhibiting pro-inflammatory factors: NE, IL-1β, and IL-8.

Keywords: Alpha 1-antitrypsin; IL-1β; IL-8; Polycystic ovary syndrome; Pro-inflammatory cytokines; molecular docking; neutrophil elastase.

Figure 1

- Expression of tissue and serum A1AT, NE, IL-1β, and IL-8 levels between polycystic ovarian syndrome (PCOS) cases and normal controls. A-B: The relative alpha1-antitrypsin (A1AT) and neutrophil elastase (NE) mRNA levels in the ovaries of PCOS and normal control rats. C-F: Serum A1AT, interleukin (IL)-1β, IL-8, and NE expression in PCOS cases and controls. *p<0.05, **p<0.01, ***p<0.001

Figure 2

- Comparison of serum A1AT, NE, interleukin (IL)-1beta, and IL-8 levels between polycystic ovarian syndrome cases and normal controls.

Figure 3

- The residues involved in polar interactions are labeled and shown in the stick renders. The interactions between residues are shown in yellow dashed lines. A) The complex of NE (purple) and alpha1-antitrypsin (A1AT) (blue). B) The complex of interleukin (IL)-8 (red) and alpha1-antitrypsin (blue). C) The complex of IL-1β (yellow) and A1AT (blue).

Figure 4

- Calculated interactions between the residues on the interfaces of the neutrophil elastase and alpha1-antitrypsin (A1AT) complex, the interleukin (IL)-8 and A1AT complex, and the IL-1β and A1AT complex.