Nuclear receptors: Key regulators of somatic cell functions in the ovulatory process

Hughes, Camilla H K; Murphy, Bruce D.

doi:10.1016/j.mam.2020.100937

Cited by 27 publications

(15 citation statements)

References 297 publications

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“…Although a low level of PLA signal suggests that PGR and LRH1 are closely co-localised, a functional interaction is less likely as they possess different windows of expression in granulosa cells (PGR is completely absent in granulosa cells prior to the LH surge whereas LRH1 is expressed from primordial stage up to corpus luteum 49 . In support of this, less than 20% of PGR-regulated genes were also found to be LRH1 targets in peri-ovulatory granulosa cells 2 . On the other hand, JUN/FOS transcription factors are highly induced by the LH surge in granulosa cells, similar to PGR 35,50 .…”

Section: Discussionmentioning

confidence: 69%

“…The mechanism of ovulation begins with the activation of cAMP-dependent kinase (PKA) and extracellular regulated kinase (ERK) signalling cascades in granulosa cells of the follicle in response to the pituitary LH surge 1 . These signals result in the induction of an array of transcriptional regulators that collectively mediate complete structural remodelling of the ovarian follicle and the resumption of oocyte meiotic maturation 2 . Meanwhile, follicular granulosa cells undergo pervasive differentiation and rapid neoangiogenesis to form the corpus luteum, a transient endocrine organ that produces high levels of progesterone to promote uterine receptivity 3 and mammary gland maturation 4 in preparation for pregnancy and lactation.…”

Section: Introductionmentioning

confidence: 99%

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Progesterone receptor-A isoform interaction with RUNX transcription factors controls chromatin remodelling at promoters during ovulation

Dinh

Breen

Nicol

et al. 2021

Preprint

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Progesterone receptor (PGR) plays diverse roles in reproductive tissues and thus coordinates mammalian fertility. In the ovary, acutely induced PGR is the key determinant of ovulation through transcriptional control of a unique set of genes that culminates in follicle rupture. However, the molecular mechanisms for PGR specialised function in ovulation is poorly understood. To address this, we assembled a detailed genomic profile of PGR action through combined ATAC-seq, RNA-seq and ChIP-seq analysis in wildtype and isoform-specific PGR null mice. We demonstrated the unique action of PGR-A isoform in the ovary through a transcriptional complex involving physical interaction with RUNX and JUN/FOS transcription factors. The assembly of this unique complex directs targeting of PGR binding to proximal promoter regions and enables chromatin accessibility, leading to ovulatory gene induction. This PGR signalling mechanism is specific to ovulation and provides potential targets for infertility treatments as well as new contraceptives that block ovulation.

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Section: Discussionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Progesterone receptor-A isoform interaction with RUNX transcription factors controls chromatin remodelling at promoters during ovulation

Dinh

Breen

Nicol

et al. 2021

Preprint

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“…Nuclear receptors play a very important role in the regulation of the final stage of ovarian follicle growth. Under the influence of follicle stimulating hormone, nuclear receptors promote the proliferation and differentiation of granulosa cells and the synthesis of steroids ( Hughes and Murphy, 2021 ). WSYR may promote oocyte maturation and embryo development through these biological processes.…”

Section: Resultsmentioning

confidence: 99%

Wenshenyang recipe treats infertility through hormonal regulation and inflammatory responses revealed by transcriptome analysis and network pharmacology

Xie

Zhao²,

Huang

et al. 2022

Front. Pharmacol.

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The Wenshenyang recipe (WSYR) has the effect of treating infertility, but the mechanisms underlying this activity have not been fully elucidated. In this study, network pharmacology and RNA sequencing were combined, with database-based “dry” experiments and transcriptome analysis-based “wet” experiments used conjointly to analyse the mechanism of WSYR in the treatment of infertility. In the dry analysis, 43 active compounds in WSYR and 44 therapeutic targets were obtained through a database search, 15 infertility pathways were significantly enriched, and key targets, such as ESR1, TP53, AKT1, IL-6, and IL-10 were identified. Then the wet experiments were performed to detect the expression changes of the 412 genes from 15 infertility pathways identified by dry analysis. HK-2 cells were treated with the three herbs of WSYR and subjected to targeted RNA sequencing. Based on the results, 92 of the 412 genes in 15 infertility pathways were identified as DEGs. Additionally, key targets, such as ESR2, STAT1, STAT3, and IL6, were also identified in the wet experiments. RT-qPCR experiments further verified that WSYR played an anti-inflammatory role by upregulating IL-4 and IL-10 and Epimedium brevicornu Maxim (Yinyanghuo) showed broader effect than Drynaria fortunei (Kunze) J. Sm (Gusuibu) and Cistanche deserticola Y.C.Ma (Roucongrong). By screening compounds of WSYR using molecular docking models of ESR1 and ESR2, it was further found that xanthogalenol in Gusuibu, arachidonate in Roucongrong, and anhydroicaritin in Yinyanghuo had good affinity for estrogen receptors. These findings provide evidence for an estrogen-regulating role of the three herbs in WSYR.

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“…In GCs, androgens are converted into oestrogens, mainly in the form of oestradiol (E2) under the stimulation of follicle-stimulating hormone (FSH). Increased levels of E2 bind to ERα, ERβ and GPER, which further increases the production of LH, leading to a surge of LH in GCs and TCs [ 29 ]. This condition stimulates the proliferation and differentiation of GCs and TCs, which is the final stage of follicle development, followed by the ovulation stage [ 30 ].…”

Section: Characteristics Of Sex Steroid Receptorsmentioning

confidence: 99%

“…The remaining unconverted androgen in the GCs binds to AR in the GCs. AR activation in the TCs and GCs stimulates the proliferation and differentiation of the cells into mature follicles [ 29 ]. Evidence has shown intense AR expression in TCs and GCs during the early/mid proliferative stage [ 70 ].…”

Section: Characteristics Of Sex Steroid Receptorsmentioning

confidence: 99%

Sex Steroid Receptors in Polycystic Ovary Syndrome and Endometriosis: Insights from Laboratory Studies to Clinical Trials

et al. 2022

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Polycystic ovary syndrome (PCOS) and endometriosis are reproductive disorders that may cause infertility. The pathology of both diseases has been suggested to be associated with sex steroid hormone receptors, including oestrogen receptors (ER), progesterone receptors (PRs) and androgen receptors (ARs). Therefore, with this review, we aim to provide an update on the available knowledge of these receptors and how their interactions contribute to the pathogenesis of PCOS and endometriosis. One of the main PCOS-related medical conditions is abnormal folliculogenesis, which is associated with the downregulation of ER and AR expression in the ovaries. In addition, metabolic disorders in PCOS are caused by dysregulation of sex steroid hormone receptor expression. Furthermore, endometriosis is related to the upregulation of ER and the downregulation of PR expression. These receptors may serve as therapeutic targets for the treatment of PCOS-related disorders and endometriosis, considering their pathophysiological roles. Receptor agonists may be applied to increase the expression of a specific receptor and treat endometriosis or metabolic disorders. In contrast, receptor antagonist functions to reduce receptor expression and can be used to treat endometriosis and induce ovulation. Understanding PCOS and the pathological roles of endometriosis sex steroid receptors is crucial for developing potential therapeutic strategies to treat infertility in both conditions. Therefore, research should be continued to fill the knowledge gap regarding the subject.

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Nuclear receptors: Key regulators of somatic cell functions in the ovulatory process

Cited by 27 publications

References 297 publications

Progesterone receptor-A isoform interaction with RUNX transcription factors controls chromatin remodelling at promoters during ovulation

Progesterone receptor-A isoform interaction with RUNX transcription factors controls chromatin remodelling at promoters during ovulation

Wenshenyang recipe treats infertility through hormonal regulation and inflammatory responses revealed by transcriptome analysis and network pharmacology

Sex Steroid Receptors in Polycystic Ovary Syndrome and Endometriosis: Insights from Laboratory Studies to Clinical Trials

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