Sleep apnea 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 multiple 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.

To study the effects of sleep apnea induced immune dysfunction on the reproductive system of female rats.

The research period was from January 2023 to December 2024. Thirty 4-6 month female SD rats (SPF grade) 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 (ERα) and estrogen receptor beta (ERβ) 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 and the growth and development of offspring mice were analyzed.

Compared with the blank control group, the long-term groups showed an increased rate of dysregulation in the estrous cycle (P<0.017). 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 ERβ 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.

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.

睡眠呼吸暂停是临床高发的睡眠障碍性疾病，随生活方式改变发病率持续攀升，可引发心血管、代谢等多系统损伤。近年来发现女性睡眠呼吸暂停患者常出现月经紊乱、不孕等生殖功能异常，但睡眠呼吸暂停诱导雌性生殖系统损伤的免疫调控机制，尤其是树突状细胞（DCs）介导的免疫应答异常的作用，仍缺乏深入解析。

研究睡眠呼吸暂停所致的相关障碍性免疫损伤对雌性大鼠生殖系统的影响。

2023—2024年，将30只动情周期规律的4~6月龄雌性SD大鼠（SPF级）随机分为空白对照组、短期组、长期组，各10只，空白对照组正常饲养6周；短期组正常饲养3周后，在制备睡眠呼吸暂停模型基础上饲养3周；长期组在制备睡眠呼吸暂停模型基础上饲养6周。分析各组大鼠动情周期，卵巢组织雌激素受体α亚型（ERα）、雌激素受体β亚型（ERβ）表达量，卵巢组织中卵泡数量；观察DCs迁徙能力、DCs刺激同种T淋巴细胞增殖反应（MLR）能力及DCs内Toll样受体4（TLR4）、RelB表达量变化，并分析各组大鼠生育力和子代小鼠生长发育情况。

与空白对照组比较，长期组动情周期紊乱率升高（P<0.017）。与空白对照组比较，短期组、长期组卵巢组织ERα、ERβ表达量降低（P<0.05）；与短期组比较，长期组卵巢组织ERα、ERβ表达量降低（P<0.05）。与空白对照组比较，短期组、长期组原始卵泡、初级卵泡、窦状卵泡数目降低，闭锁卵泡数目增加（P<0.05）；与短期组比较，长期组原始卵泡、初级卵泡、窦状卵泡数目降低，闭锁卵泡数目增加（P<0.05）。与空白对照组比较，短期组、长期组DCs迁徙比例降低，MLR升高（P<0.05）；与短期组比较，长期组DCs迁徙比例降低，MLR升高（P<0.05）。与空白对照组比较，短期组、长期组DCs内TLR4、RelB表达量均升高（P<0.05）；与短期组比较，长期组DCs内TLR4、RelB表达量均升高（P<0.05）。与空白对照组比较，长期组妊娠率、活产率均降低（P<0.05）。3组活产子代小鼠出生21 d每日体质量均有所升高，但与空白对照组比较，短期组与长期组生长迟滞，尤其是长期组。

睡眠呼吸暂停可引起雌性大鼠卵巢功能减退，降低生育力，推测其可能通过改变DCs迁徙能力来激活TLR4/RelB引起免疫损伤，从而导致生殖系统紊乱。