Letrozole-Induced Polycystic Ovary Syndrome Attenuates Cystathionine-β Synthase mRNA and Protein Abundance in the Ovaries of Female Sprague Dawley Rats

Bries, Amanda; Webb, J. L.; Vogel, Brooke; Carrillo, Claudia; Keating, Aileen F.; Pritchard, Samantha; Roslan, Gina; Miller, Joshua W.; Schalinske, Kevin L.

doi:10.1093/jn/nxab038

Cited by 3 publications

(1 citation statement)

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“…Our previous study indicated that rats with administration of LET subcutaneously for 12 weeks showed both the reproductive and metabolic alterations as PCOS patients have [18]. Although many studies have used LET-induced animal models to study the pathogenesis and pharmacological treatment related to PCOS, most of them focus on the characteristics related to the end induction of the model [19][20][21][22][23][24], and only a few experiments have been conducted to investigate the pathological mechanisms of LET-induced PCOS model animals at different time points [25,26]. Further, few studies work on investigating the regulation of inflammatory response during the pathogenesis of PCOS.…”

Section: Introductionmentioning

confidence: 99%

TLR4/NF-κB Signaling Contributes to the Inflammation in Ovary and Inguinal Fats of Polycystic Ovary Syndrome

Sun

Pan

Kuang

et al. 2022

Preprint

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BackgroundPolycystic ovary syndrome (PCOS) is a complex reproductive endocrine disorder. It has highly heterogeneous clinical manifestations which are characterized by biochemical hyperandrogenemia, obesity, insulin resistance, dyslipidemia, anovulation, and polycystic ovaries. However, the etiologies of PCOS are still unclear. Recently, studies have found that the low-grade inflammation contributed to the occurrence of PCOS, and as a critical biomarker indicated the endocrine disruptions in PCOS.ObjectiveThis study is aimed to investigate the processes and mediators of inflammation in contributing to the development of PCOS.MethodsLetrozole (LET) induced PCOS rat model was used in this study. Body weight, body temperature, inguinal fats weight, fasting glucose level, ovarian morphology, NF-κB signaling target genes in ovary, and protein expression levels of TLR4 and NF-κB in ovarian and inguinal fats were measured in rats with placebo and LET administrations for 6 and 12 weeks.ResultsPCOS rats, especially with LET intervention for 12 weeks, had higher body weight, inguinal fats weight and fasting glucose level compared to control group. The protein expression levels of TLR4 and NF-κB in cytoplasm of ovarian and inguinal fats were increased in LET-induced PCOS rats compared to control groups, while NF-κB in nucleus were reduced in PCOS rats. The expressions of ACTB, C3, CXCL3, NQO1 and SELP in ovarian were statistically different in PCOS rats induced by LET compared to control groups. ConclusionThese findings indicated that stimulating TLR4/NF-κB pathway in inguinal fats and ovary tissues contributed to the increased inflammation in LET-induced PCOS rats, which, in turn, exacerbated the phenotype of PCOS including weight gain, adipose tissue accumulation, hyperglycemia and follicular dysplasia.

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