Establishment and Mechanism Study of a Primary Ovarian Insufficiency Mouse Model using Lipopolysaccharide

Abstract

Background: This study aimed to establish a lipopolysaccharide (LPS)-induced primary ovarian insufficiency (POI) mouse model and to investigate the underlying mechanism.Methods: 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, and cyclophosphamide (CTX; 150 mg/kg) once weekly for 2 weeks. Ovarian function was assessed by measuring the length of the estrous cycle, the number of primordial follicles, and the levels of serum pituitary/ovarian hormones. Expression and production of interleukin 1β (IL-1β) 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 mouse ovaries.Results: Like CTX, both low- and high-dose LPS administration 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 administration promoted granulosa cell apoptosis and ovarian fibrosis in mice. However, LPS but not CTX significantly promoted IL-1β expression and production in mice. Moreover, LPS treatment but not CTX significantly enhanced TLR, p-p65, p65, and MyD88 protein 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 stimulation in the above-mentioned effects.Conclusions: LPS induces ovarian inflammation, fibrosis, and granulosa cell apoptosis and can be used to establish a POI model in mice.

Zinc-nanoparticles alleviate the ovarian damage induced by bacterial lipopolysaccharide (LPS) in pregnant rats and their fetuses

“… 2019 ; Lv et al. 2021 ), the ovaries and uteruses of cows (Magata 2020 ), the uteruses of mice (Jaiswal et al. 2009 ; Wolfson et al.…”

Identification and Validation of Autophagy-Related Genes in Primary Ovarian Insufficiency by Gene Expression Profile and Bioinformatic Analysis

“…Lipopolysaccharide (LPS) has been revealed to play an essential role in causing hormonal imbalance, ovarian dysfunction, and even infertility [7]. It can be utilized to induce primary ovarian insufficiency (POI) in mouse through causing fibrosis, inflammation, and granulosa cell apoptosis [8]. The exposure to LPS can lead to cell programed death of granulosa cells such as apoptosis and pyroptosis, which contribute to steroidogenesis dysfunction and reproduction failure finally [9].…”

Lipid Polysaccharides have a Detrimental Effect on the Function of the Ovaries and Uterus in Mice through Increased Pro-Inflammatory Cytokines

“…LPS secrete inflammatory cytokines such as TNF-α, IL-1α, and IL-1β to stimulate apoptosis directly and inhibit steroid production, which has a detrimental effect on mammalian ovaries ( Roby & Terranova, 1988 ; Gottschall et al, 1989 ; Pate, 1995 ; Kaipia et al, 1996 ). LPS stimulation induces fibrosis of the ovary and apoptosis of granulocytes ( Lv et al, 2021 ). In addition, LPS affects the secretion of sex steroid hormones in both stromal cells and granulocytes, leading to ovarian dysfunction ( Taylor & Terranova, 1996 ).…”