Role of epigenetic modifications in the aberrant CYP19A1 gene expression in polycystic ovary syndrome

Hosseini, Elham; Shahhoseini, Maryam; Afsharian, Parvaneh; Karimian, Leila; Ashrafi, Mahnaz; Mehraein, Fereshteh; Afatoonian, Reza

doi:10.5114/aoms.2019.86060

Cited by 36 publications

(17 citation statements)

References 42 publications

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“…Medical therapy includes combined hormonal contraceptives spironolactone and metformin [96], oral contraceptive pills, and local treatments for hirsutism and acne [97]. The latest research showed that aromatase expression may be affected by epigenetic modifications and the binding of differential ERβ to the proximal CYP19A1 promoter, possibly involved in enhanced aromatase transcription during ovarian stimulation in PCOS patients [98].…”

Section: Ers and Female Reproductive Diseasesmentioning

confidence: 99%

Estrogen-Receptor Expression and Function in Female Reproductive Disease

Tang

Zhang

Lian

et al. 2019

Cells

158

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Estrogen receptors (ER) include ER alpha, ER beta and new membrane receptor G protein-coupled receptor 30 (GPR30). Estrogen receptors are key receptors to maintain ovarian granulosa cell differentiation, follicle and oocyte growth and development, and ovulation function. The abnormal functions of estrogen, its receptors, and estradiol synthesis-related enzymes are closely related to clinical reproductive endocrine diseases, such as polycystic ovary syndrome (PCOS) and endometriosis (EMS). At present, hormone therapy is the main treatment for ovarian-related diseases, and a stable hormone environment is established by regulating ovarian function. In recent years, some estrogen-related drugs have made great progress, such as clomiphene, which is a nonsteroidal antiestrogen drug in clinical application. This article elaborates on the regulatory role of estrogen and its nuclear receptors and membrane receptors in oocyte development, especially female reproductive diseases related to the abnormal expression of estrogen and its receptors. We also highlighted the latest advances of treatment strategy for these diseases and the application of related targeted small molecule drugs in clinical research and treatment, so as to provide reference for the treatment of female reproductive diseases.

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Section: Ers and Female Reproductive Diseasesmentioning

confidence: 99%

Estrogen-Receptor Expression and Function in Female Reproductive Disease

Tang

Zhang

Lian

et al. 2019

Cells

158

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“…The growth of the ovarian follicle fails to succeed in completing its maturation for ovulation, and most follicles are arrested at the antral stage [9]. Moreover, hyperinsulinemia, as the main feature of PCOS, leads to the over-production of ovarian androgens [10] and has a negative impact on artery function and cardiovascular diseases [11].…”

Section: Introductionmentioning

confidence: 99%

The effect of clomiphene citrate, herbal mixture, and herbal mixture along with clomiphene citrate on clinical and para-clinical parameters in infertile women with polycystic ovary syndrome: a randomized controlled clinical trial

Ainehchi

Khaki

Ouladsahebmadarek

et al. 2020

aoms

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Introduction: To evaluate the effect of a herbal mixture (i.e., Mentha spicata, Zingiber officinale, Cinnamomum zeylanicum, and Citrus sinensis) alone and in combination with clomiphene citrate (CC) compared to CC on the treatment of polycystic ovary syndrome (PCOS). Material and methods: This single-blind randomized clinical trial was conducted on 60 infertile participants with PCOS who were randomly divided into three groups. After spontaneous or progestin-induced withdrawal bleeding, group 1 (n = 20) received routine treatment with CC (50-150 mg) for three menstrual cycles from the 3 rd to 5 th day of menstruation for 5 days while group 2 (n = 20) and group 3 (n = 20) received herbal mixture capsules 700 mg/day and the herbal mixture along with CC for 3 months, respectively. Finally, several related parameters were measured, including the level of sex steroids, homeostatic model assessment for insulin resistance (HOMA-IR), lipid profile (primary outcomes), thyroid hormones, and clinical features. The analysis was based on intention-to-treat analysis. Results: No statistically significant differences were observed between the groups in terms of socio-demographic characteristics. However, after adjustment for baseline, luteinizing hormone (aMD = 4.9; 95% CI: 3.7-6.2), luteinizing hormone/follicle-stimulating hormone (aMD = 0.9; 95% CI: 0.7-1.2), total testosterone (aMD =-0.12; 95% CI:-0.2 to-0.01) in group 2 and free testosterone (aMD =-6.0; 95% CI:-9.7 to-2.3) in group 3 revealed a significant difference compared to group 1. In addition, HOMA-IR in group 2 (aMD =-1.3; 95% CI:-2.4 to-0.2) decreased significantly compared to group 1. Further, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol decreased significantly

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“…In mural GC, CYP19A1 expression is described to be either unmodified [ 91 , 92 ] or down-regulated [ 90 , 93 , 94 ] in PCOS when compared to non-PCOS. However, in cumulus GC, CYP19A1 mRNA levels are higher in PCOS when compared to heathy women [ 95 ]. These data suggest the existence of differential CYP19A1 expression regulations in GC, depending on their proximity to the oocyte.…”

Section: Importance Of E2 Signaling In Pcosmentioning

confidence: 99%

Estradiol Signaling at the Heart of Folliculogenesis: Its Potential Deregulation in Human Ovarian Pathologies

Chauvin

Cohen‐Tannoudji

Guigon

2022

IJMS

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Estradiol (E2) is a major hormone controlling women fertility, in particular folliculogenesis. This steroid, which is locally produced by granulosa cells (GC) within ovarian follicles, controls the development and selection of dominant preovulatory follicles. E2 effects rely on a complex set of nuclear and extra-nuclear signal transduction pathways principally triggered by its nuclear receptors, ERα and ERβ. These transcription factors are differentially expressed within follicles, with ERβ being the predominant ER in GC. Several ERβ splice isoforms have been identified and display specific structural features, which greatly complicates the nature of ERβ-mediated E2 signaling. This review aims at providing a concise overview of the main actions of E2 during follicular growth, maturation, and selection in human. It also describes the current understanding of the various roles of ERβ splice isoforms, especially their influence on cell fate. We finally discuss how E2 signaling deregulation could participate in two ovarian pathogeneses characterized by either a follicular arrest, as in polycystic ovary syndrome, or an excess of GC survival and proliferation, leading to granulosa cell tumors. This review emphasizes the need for further research to better understand the molecular basis of E2 signaling throughout folliculogenesis and to improve the efficiency of ovarian-related disease therapies.

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Role of epigenetic modifications in the aberrant CYP19A1 gene expression in polycystic ovary syndrome

Cited by 36 publications

References 42 publications

Estrogen-Receptor Expression and Function in Female Reproductive Disease

Estrogen-Receptor Expression and Function in Female Reproductive Disease

The effect of clomiphene citrate, herbal mixture, and herbal mixture along with clomiphene citrate on clinical and para-clinical parameters in infertile women with polycystic ovary syndrome: a randomized controlled clinical trial

Estradiol Signaling at the Heart of Folliculogenesis: Its Potential Deregulation in Human Ovarian Pathologies

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