Effect of hypothyroidism on CYP51 and FSHR expression in rat ovary

Weng, Xuechun; Ma, Xiaoshu; Wang, Qiaozhi; Xu, Kaili; Hu, Xusong; Liu, Wenbo; Zhang, Cheng

doi:10.1016/j.theriogenology.2019.07.012

Cited by 6 publications

(3 citation statements)

References 40 publications

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“…Recent GWAS among patients with HT identified SNP rs12713034 in the FSHR gene that is associated with the presence of anti-thyroid antibodies ( 146 ). In addition, hypothyroidism has been found to decrease FSH and E 2 levels and alter FSHR-mediated expression of CYP51 , a key enzyme involved in sterols and steroids biosynthesis during folliculogenesis and oocyte maturation, which is regulated by FSH ( 272 ); thus providing a further link between the functions of the ovaries and thyroid gland.…”

Section: Joint Prevalence Of Polycystic Ovary Syndrome and Autoimmunementioning

confidence: 99%

Genetic Susceptibility to Joint Occurrence of Polycystic Ovary Syndrome and Hashimoto’s Thyroiditis: How Far Is Our Understanding?

Żeber‐Lubecka

Hennig

2021

Front. Immunol.

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Polycystic ovary syndrome (PCOS) and Hashimoto’s thyroiditis (HT) are endocrine disorders that commonly occur among young women. A higher prevalence of HT in women with PCOS, relative to healthy individuals, is observed consistently. Combined occurrence of both diseases is associated with a higher risk of severe metabolic and reproductive complications. Genetic factors strongly impact the pathogenesis of both PCOS and HT and several susceptibility loci associated with a higher risk of both disorders have been identified. Furthermore, some candidate gene polymorphisms are thought to be functionally relevant; however, few genetic variants are proposed to be causally associated with the incidence of both disorders together.

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Section: Joint Prevalence Of Polycystic Ovary Syndrome and Autoimmunementioning

confidence: 99%

Genetic Susceptibility to Joint Occurrence of Polycystic Ovary Syndrome and Hashimoto’s Thyroiditis: How Far Is Our Understanding?

Żeber‐Lubecka

Hennig

2021

Front. Immunol.

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“…Although “RT1-CE2” is a mouse-derived gene, it contains a series of characteristic non-classical major histocompatibilty complex (MHC) molecules, which may be related to immune inflammatory response ( Dai et al, 2018 ), which may provide a direction for our future research on the population. CYP51 is a key enzyme involved in sterol and steroid biosynthesis in follicular development and oocyte maturation, thyroid hormone and gonadotropin levels have a regulatory effect on the process of follicle formation and oocyte maturation involved in CYP51 ( Weng et al, 2019 ) . In addition, other studies have found that the abnormal expression of Cytochrome P450 Family 19 Subfamily A Member 1 (CYP19A1), Epidermal Growth Factor Receptor (EGFR), Estrogen Receptor 2 (ESR2), Fos Proto-Oncogene, AP- 1 Transcription Factor Subunit (FOS), and Insulin-like growth factor 1 (IGF1) related to the steroid pathway may also be related to the ovarian dysfunction of endometriosis ( Roy et al, 2015 ) It is noteworthy that the genetic changes in ovaries are at least partly due to steroid biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

Phthalate exposure and risk of ovarian dysfunction in endometriosis: human and animal data

Zhu

et al. 2023

Front. Cell Dev. Biol.

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Objective: We aimed to explore the correlations between and possible mechanisms of common environmental endocrine disruptors, phthalates, and ovarian dysfunction in endometriosis.Methods: Subjects were included in the case group (n = 107) who were diagnosed with endometriosis by postoperative pathology in Fujian Maternal and Child Hospital from February 2018 to February 2021, and the women who were excluded from endometriosis by surgery were as the control group (n = 70). The demographic information of the subjects were evaluated by questionnaire, and the clinical characteristics were evaluated by medical records and 3-year follow-up results. Gas chromatography‒mass spectrometry was used to quantify 10 metabolites of phthalates, including dimethyl ortho-phthalate (DMP), mono-n-methyl phthalate (MMP), dioctyl ortho-phthalate (DEP), mono-ethyl phthalate (MEP), di-n-butyl ortho-phthalate (DBP), mono-butyl phthalate (MBP), benzylbutyl phthalate (BBzP), mono-benzyl; phthalate (MBzP), diethylhexyl phthalate (DEHP) and mono-ethylhexyl phthalate (MEHP), in the urine samples of the subjects. Furthermore, a total of 54 SD rats were exposed to DEHP 0, 5, 50, 100, 250, 500, 1,000, 2000, and 3,000 mg/kg/day for 2 weeks. The SD rats’ body weight, oestrus cycle changes, and serum anti-mullerian hormone (AMH) levels were evaluated. After sacrifice, the mass index of the rat uterus and bilateral ovaries were calculated. Finally, bioinformatics analysis of rat ovarian tissues was performed to explore the possible mechanism. SPSS 24.0 (IBM, United States) was used for data analysis. p-value <0.05 was considered statistically significant.Results: The human urinary levels of DMP (p < 0.001), MMP (p = 0.001), DEP (p = 0.003), MEP (p = 0.002), DBP (p = 0.041), MBP (p < 0.001), BBzP (p = 0.009), DEHP (p < 0.001), and MEHP (p < 0.001) were significantly higher in women with endometriosis than in controls. Notably, DEHP was a significant risk factor for endometriosis (OR: 11.0, 95% CI: 5.4–22.6). The area under the ROC curve increased when multiple phthalates were diagnosed jointly, reaching 0.974 as the highest value, which was helpful for the diagnosis of endometriosis. In vivo experiments showed that after DEHP exposure in rats, the mass index of the ovary and uterus decreased in a dose-dependent manner; the oestrus cycle of SD rats was irregularly prolonged and disordered; and the serum AMH level was negatively correlated with the DEHP exposure dose (Rho = −0.8, p < 0.001). Bioinformatics analysis of rat ovarian tissues showed that seven genes involved in the steroid biosynthesis pathway were upregulated and may play a negative role in ovarian function.Conclusion: Exposure to phthalates, especially DEHP, is associated with the occurrence of endometriosis and affects women’s reproductive prognosis and ovarian function. The steroid biosynthesis pathway may be related to ovarian dysfunction. The detection of phthalate in urine may become a new biological target for the diagnosis of endometriosis.

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“…A previous study showed that hypothyroidism rats had increased levels of TNF-α, IL-6, and other cytokines [ 39 ]. Therefore, we hypothesized that hypothyroidism might affect the growth, development, and differentiation of the cells in the ovarian tissue by altering the cytokine levels in vivo.…”

Section: Discussionmentioning

confidence: 99%

IFN-γ differential expression in the hypothalamus-pituitary-ovary axis of thyroidectomized rats

et al. 2022

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IFN-γ is critical for both thyroid and ovarian function, while thyroxine, secreted from the thyroid gland, regulates the ovarian function via the hypothalamus-pituitary -ovary axis. However, the effect of thyroxine on INF-γ involved in the regulation of hypothalamic pituitary ovarian axis ovarian function is hitherto unknown. Therefore, we set up three groups including a sham-operated group, an experimental thyroidectomized group, and an experimental thyroidectomized group treated with T4 to reveal the IFN-γ expression levels in the in the hypothalamus, pituitary gland, and ovary by immunohistochemical staining, RT-PCR, and Western blotting. IFN-γ-like immunoreactive-positive substances were visualized in the hypothalamus, pituitary gland, and ovary, which were located mainly in the cytoplasm of the hypothalamic neurons anterior pituitary cells, luteal cells, and theca cells in the ovary of hypothyroidism rats, respectively. RT-PCR and Western blotting showed that the rats in the experimental thyroidectomized group treated with T4 had significantly elevated expression of IFN-γ at both the mRNA and protein levels. Thyroxine affects the expression of IFN-γ in the thalamus-pituitary-ovarian axis, which may influence the secretion of IFN-γ to regulate ovarian function during hypothyroidism. This work highlights the potential effect of thyroxine on the involvement of INF-γ in the modulation of the ovarian function in the hypothalamic-pituitary-ovarian axis.

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Effect of hypothyroidism on CYP51 and FSHR expression in rat ovary

Cited by 6 publications

References 40 publications

Genetic Susceptibility to Joint Occurrence of Polycystic Ovary Syndrome and Hashimoto’s Thyroiditis: How Far Is Our Understanding?

Genetic Susceptibility to Joint Occurrence of Polycystic Ovary Syndrome and Hashimoto’s Thyroiditis: How Far Is Our Understanding?

Phthalate exposure and risk of ovarian dysfunction in endometriosis: human and animal data

IFN-γ differential expression in the hypothalamus-pituitary-ovary axis of thyroidectomized rats

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