Department of Gynaecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
Department of Obstetrics and Gynecology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Anal Cell Pathol (Amst). 2021 Nov 16;2021:1781532. doi: 10.1155/2021/1781532. eCollection 2021.
This study is aimed at establishing a lipopolysaccharide- (LPS-) induced primary ovarian insufficiency (POI) mouse model and investigating the underlying mechanism. C57BL/6N female mice were intraperitoneally injected with low-dose LPS (0.5 mg/kg) once daily for 14 days, high-dose LPS (2.5 mg/kg) twice weekly for 2 weeks, or cyclophosphamide (CTX; 150 mg/kg) once weekly for 2 weeks. Ovarian function was assessed by measuring the length of estrous cycle, the number of primordial follicles, and the levels of serum hormones. Expression and production of interleukin 1 (IL-1) were determined to evaluate ovarian inflammation. Histopathological examination was performed to examine ovarian fibrosis. TUNEL assay was carried out to evaluate granulosa cell apoptosis. Western blotting was performed to measure the levels of inflammation-, fibrosis-, and apoptosis-related proteins in the mouse ovaries. Like CTX, both low- and high-dose LPS significantly impaired ovarian functions in mice, as evidenced by extended lengths of estrous cycles, reduced counts of primordial follicles, and alterations in the levels of serum hormones. Also, LPS promoted granulosa cell apoptosis and ovarian fibrosis in mice. However, LPS but not CTX promoted IL-1 expression and production in mice. Moreover, LPS but not CTX enhanced TLR, p-p65, p65, and MyD88 expression in mouse ovaries, suggesting that LPS differs from CTX in triggering ovarian inflammation. In general, continuous low-dose LPS stimulation was less potent than high-dose LPS to affect the ovarian functions. In conclusion, LPS may induce ovarian inflammation, fibrosis, and granulosa cell apoptosis and can be used to establish a POI model in mice.
本研究旨在建立脂多糖（LPS）诱导的原发性卵巢功能不全（POI）小鼠模型，并探讨其潜在机制。C57BL/6N 雌性小鼠每日腹腔注射低剂量 LPS（0.5mg/kg）一次，连续 14 天；或每周两次腹腔注射高剂量 LPS（2.5mg/kg），连续 2 周；或每周腹腔注射环磷酰胺（CTX；150mg/kg）一次，连续 2 周。通过测量动情周期的长度、原始卵泡的数量以及血清激素水平来评估卵巢功能。通过测定白细胞介素 1（IL-1）的表达和产生来评估卵巢炎症。进行组织病理学检查以检查卵巢纤维化。通过 TUNEL 测定评估颗粒细胞凋亡。通过 Western blot 测定测量小鼠卵巢中炎症、纤维化和凋亡相关蛋白的水平。与 CTX 一样，低剂量和高剂量 LPS 均显著损害了小鼠的卵巢功能，表现为动情周期延长、原始卵泡数量减少以及血清激素水平改变。此外，LPS 促进了小鼠颗粒细胞凋亡和卵巢纤维化。然而，LPS 但不是 CTX 促进了小鼠 IL-1 的表达和产生。此外，LPS 但不是 CTX 增强了小鼠卵巢中 TLR、p-p65、p65 和 MyD88 的表达，表明 LPS 在触发卵巢炎症方面与 CTX 不同。总的来说，持续低剂量 LPS 刺激的作用不如高剂量 LPS 强烈，对卵巢功能的影响较小。总之，LPS 可能诱导卵巢炎症、纤维化和颗粒细胞凋亡，可用于建立小鼠 POI 模型。
