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Study on reproductive hormone disorder causing N-glycan structure change by swainsonine poisoning


 Background: Glycosylation and glycan composition play an important role in the biological properties of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Swainsonine (SW) causes oligosaccharide accumulation and incomplete glycoprotein processing. Previous research has shown that SW reduces serum progesterone concentrations in pregnant livestock. However, we do not know how SW affects the secretion of reproductive hormones.
Materials: We used primary culture of mouse endometrial epithelial cells, Real-time polymerase chain reaction, Western blot, Periodic acid-Schiff (PAS) staining, Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS), ELLSA, etc. method.
Results: In this study, we observed a significant decrease in the number of surviving fetal mice in the SW treatment group mice and a high level of carbohydrate deposition in PAS stained uterine tissue in the SW treatment group mice. Extensive vacuole degeneration can also be observed in mouse primary endometrial epithelial cell cultures in vitro after SW poisoning. MALDI-TOF-MS shows that the time of exposure to SW is prolonged, the number of di-, tri-, and tetra-complex glycosylated gradually decreases, and the number of tri- hybrid type glycosylated increases, while significantly reduced activity of glycosyltransferases and glycosidases are observed in endometrial epithelial cells. FSH and LH were significantly decreased at 7 and 15 days after pregnancy and 7 days after childbirth, the content of E2 and P4 decreased significantly at 7 days after childbirth, and the expression levels of mRNA and protein of 3β-hydroxysteroid dehydrogenase (HSD-3β) and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) also showed a significant decrease at 15 days after pregnancy and 7 days after childbirth.
Conclusions: In summary, The glycan chain structure of FSH and LH glycoprotein hormones were changed by swainsonine, which they are decreased on the expression of the limiting enzyme of steroid hormones indirectly, and ultimately lead to a decrease in the content of E2 and P4. The rate of female mice were decreased by dysfunction of the reproductive hormones.