The Role of Extracellular Vesicles in Endometriosis-related Infertility and Its Mechanism
Objective To investigate the role of extracellular vesicles(EVs)in endometriosis(EMs)-associated infertility and its mechanism.Methods Exo spinTM technology was used to isolate EVs from vaginal mucus of 10 healthy women of childbearing age(H-EVs group)and 10 patients with EMs-associated infertility(E-EVs group).With phosphate buffered saline as the control group(PBS group,n=10),human sperms were co-cultured with H-EVs,E-EVs and PBS,respectively,and sperm motility of the 3 groups was evaluated using computer-assisted semen analysis and eosin staining.To construct an EMs mouse model,30 EMs mice were randomly divided into the model group(M group),the vaginal transplantation of H-EVs group(H-EVs-VT group),and the E-EVs vaginal transplantation group(E-EVs-VT group),with 10 mice in each group;medical absorbable gelatin sponges containing 60 uL of PBS,60 μL of H-EVs solution,and 60 μL of E-EVs solution were delivered into the vagina of female mice in the 3 groups,respectively;these solutions were injected for 1 month;the male and female mice were then paired in the same cage(4∶1 ratio of male to female);the uterus and ovary tissues of the female mice were collected on the 9th day of gestation,and the fertility of the female mice in the four groups was compared by histopathology,flow cytometry,real-time quantitative reverse transcription PCR and protein blotting.Results EVs in H-EVs group and E-EVs group exhibited circular or elliptical structures with a diameter of 50～200 nm.E-EVs reduced sperm motility and survival rate,while H-EVs increased sperm motility(P＜0.05).Animal experiments shown that compared with the NC group,E-EVs induced the release of pro-inflammatory factors TGF β1,IL-6,IL-17A and transcription factor ROR-y t,resulting in the Th17/Treg imbalance and decreasing the pregnancy rate and the number of embryos implanted in EMs mice(P＜0.05),whereas H-EVs increased the expression of anti-inflammatory factor IL-10 and transcription factor Foxp3,thereby alleviating the Th17/Treg imbalance and increasing the pregnancy rate and the number of embryo deposits in EMs mice(P＜0.05).Conclusion Vaginal mucus EVs can regulate sperm motility and mediate the release of EMS-associated pro-inflammatory and anti-inflammatory factors which regulate Th17/Treg balance and affect fertility.This study may provide a new explanation for the mechanism of EMs-associated infertility.
万方数据
维普
