Abstract: BACKGROUND: Epidemiological studies have found that female workers who are exposed to waste sevoflurane for a long time have reduced fertility and increased incidence of abortion and fetal deformity.
OBJECTIVE: To imitate the working environment of long-term exposure to waste sevoflurane and investigate the mechanism of embryo implantation disorder induced by low-concentration sevoflurane exposure by observing the expression of intercellular adhesion molecule 1, integrin β1, P-selectin, and matrix metalloproteinase 9 in endometrium of pregnant mice exposed to low concentrations of sevoflurane, attempting to provide a basis for clinical safe drug use and occupational protection and to lay a foundation for further research on the mechanism of inhalation anesthetics on embryo implantation at gene and molecular levels.
METHODS: Forty female Kunming mice and sixteen male Kunming mice, aged 6 weeks, weighting (20±2) g, were caged separately. Forty female mice were randomly divided into experimental group and control group. Mice in the experimental group were exposed to 0.1% sevoflurane, 6 hours per day, while those in the control group were exposed to the air. Thirty days later, the female mice in estrus were caged with mature male mice at a rate of 2:1. Whether the female mice were pregnant was observed at 7:00 am on the second day after mating. The pregnant mice were kept independently in the original condition 
(n ≥ 8 pregnant mice in each group). Mouse uterus on day 4.5 of gestation was removed and sliced for histological observation. The expression of intercellular adhesion molecule 1, integrin β1, P-selectin, and matrix metalloproteinase 9 in endometrial tissue was detected by immunohistochemistry and statistically analyzed. The average integrated absorbance value of positive reactants was calculated.
RESULTS AND CONCLUSION: In the experimental and control groups, 17 and 15 female mice were respectively found in estrus; 12 and 10 female mice respectively were found vaginal plugs after mating. Five and two female mice were found pseudopregnant on day 4.5 of gestation in the experimental and control groups, respectively. Therefore, there were 7 and 8 pregnant mice in the experimental and control groups, respectively, and the vacant value in the experimental group was replaced by the average value obtained in the same group, which would be subsequently used in the controlled trial. Immunohistochemical results showed that the endometrium (glandular epithelial cells, luminal epithelial cells and stromal cells) of all pregnant mice were positively stained brownish yellow, but the expressions of intercellular adhesion molecule 1, integrin β1, P-selectin, and matrix metalloproteinase 9 (0.019±0.007, 0.017±0.007, 0.015±0.005, 0.012±0.005) in the experimental group were significantly lower than those in the control group (0.032±0.014, 0.025±0.008, 0.021±0.007, 0.023±0.005) (P < 0.05). All these findings indicate that long-term exposure to 0.1% sevoflurane may affect the adhesion of mouse embryos to endometrium and the embryo implantation, which may be related to the inhibitory effects of sevoflurane on the expressions of intercellular adhesion molecule 1, integrin β1, P-selectin, and matrix metalloproteinase 9, causing the imbalance in endometrial immunoregulation, the invasion of trophoblast cells into the endometrium and the inhibition of endometrial decidualization, and miscarriage and bleeding due to damaged vascular endothelium.

Key words: sevoflurane, intercellular adhesion molecule 1, integrin β1, P-selectin, matrix metalloproteinase 9