关键词: 睡眠呼吸暂停, 免疫损伤, 生殖系统, 卵巢功能

Abstract: Background Sleep apnea（OSA） is a high incidence sleep disorder disease in clinic. With the change of lifestyle，the incidence rate continues to rise，which can cause cardiovascular，metabolic and other multi system damage. In recent years，it has been found that female sleep apnea patients often experience reproductive dysfunction such as menstrual disorders and infertility. However，the immune regulatory mechanism of sleep apnea induced damage to the female reproductive system，especially the abnormal immune response mediated by dendritic cells（DCs），still lacks in-depth analysis. Therefore，this study is conducted. Objective To study the effects of sleep apnea induced immune dysfunction on the reproductive system of female rats. Methods The research period was from January 2023 to December 2024. Thirty 4-6 month old female SD rats with regular estrous cycles were randomly divided into a blank control group，a short-term group，and a long-term group，with 10 rats in each group. The blank control group was fed normally for 6 weeks，the short-term group was fed for 3 weeks on the basis of preparing a sleep apnea model，and the long-term group was fed for 6 weeks on the basis of preparing a sleep apnea model. The estrous cycle of each group of rats，the expression levels of estrogen receptor alpha（ER alpha） and estrogen receptor beta（ER beta） subtypes in ovarian tissue，and the number of follicles in ovarian tissue were analyzed. the migration ability of DCs，the ability of DCs to stimulate homologous T lymphocyte proliferation response（MLR），and the changes in toll like receptor 4 （TLR4） and RelB expression levels in DCs were observed. The fertility of each group of rats and the growth and development of offspring mice were analyzed. Results Compared with the blank control group，the long-term groups showed an increased rate of dysregulation in the estrous cycle（P<0.05）. Compared with the blank control group，the expression levels of ERα and ERβ in ovarian tissues were reduced in the short-term and long-term groups（P<0.05）. Compared with the short-term group，the long-term group showed a decrease in the expression levels of ER α and ER β in ovarian tissue（P<0.05）. Compared with the blank control group，the number of primordial follicles，primary follicles，and antral follicles decreased in the short-term and long-term groups，while the number of blocked follicles increased（P<0.05）. Compared with the short-term group，the long term group showed a decrease in the number of primordial follicles，primary follicles，and antral follicles，and an increase in the number of blocked follicles（P<0.05）. Compared with the blank control group，the migration rate of DCs decreased and the MLR increased in the short-term and long-term groups（P<0.05）. Compared with the short-term group，the long-term group showed a decrease in the migration rate of DCs and an increase in MLR（P<0.05）. Compared with the blank control group，the expression levels of TLR4 and RelB in DCs in both the short-term and long-term groups increased（P<0.05）. Compared with the short-term group，the long-term group showed an increase in the expression levels of TLR4 and RelB in DCs（P<0.05）. Compared with the blank control group，the pregnancy rate and live birth rate of long-term groups decreased（P<0.05）. Three groups of live born offspring mice showed an increase in daily weight after 21 days of birth，but compared with the blank control group，the short-term and long-term groups showed growth retardation，especially the long-term group. Conclusion Sleep apnea can cause ovarian dysfunction and reduced fertility in female rats，suggesting that it may activate TLR4/RelB by altering the migration ability of DCs，leading to immune damage and reproductive system disorders.

Key words: Sleep apnea, Immune damage, Reproductive system, Ovarian function