The Ovulatory Signal Precipitates LRH-1 Transcriptional Switching Mediated by Differential Chromatin Accessibility

Bianco, Stéphanie; Bellefleur, Anne‐Marie; Beaulieu, Élaine; Beauparlant, Charles Joly; Bertolin, Kalyne; Droit, Arnaud; Murphy, Bruce D.; Gévry, Nicolas

doi:10.1016/j.celrep.2019.07.088

Cited by 25 publications

(14 citation statements)

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“…Liver receptor homolog-1 (LRH-1, NR5A2) is one of two members of the NR5A receptor subclass, sharing a high degree of sequence identity (DBD, 95%; LBD, 76%) with steroidogenic factor-1 (SF-1, NR5A1) (Sablin et al, 2003). Both LRH-1 and SF-1 contribute to regulating steroidogenesis, but recent evidence has shown that LRH-1 plays a far more ubiquitous role also contributing to the regulation of bile acid, glucose, and ll cholesterol homeostasis (Oosterveer et al, 2012;Stein et al, 2014;Miranda et al, 2018), embryogenesis (Fayard et al, 2004), ovulation (Bianco et al, 2019), pregnancy (Zhang et al, 2013;Meinsohn et al, 2019), pancreatic and breast cancer (Lai et al, 2013;Pang et al, 2017;, inflammatory bowel disease (Bayrer et al, 2018), type I and II diabetes (Lee et al, 2011;Cobo-Vuilleumier et al, 2018), and nonalcoholic fatty liver disease (Stein et al, 2017). In contrast to classical dimeric nuclear receptors, NR5A receptors are obligate monomers that recognize a 9-bp motif containing a 5 0 -extension past the classical AGGYCR nucleotide sequence (Fayard et al, 2004;Solomon et al, 2005;Little et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Integrated Structural Modeling of Full-Length LRH-1 Reveals Inter-domain Interactions Contribute to Receptor Structure and Function

et al. 2020

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Section: Introductionmentioning

confidence: 99%

Integrated Structural Modeling of Full-Length LRH-1 Reveals Inter-domain Interactions Contribute to Receptor Structure and Function

et al. 2020

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“…Saxena et al reported that LRH-1 stimulateed the progesterone biosynthetic pathway during granulosa cell differentiation[10]. By employing a systems biology approach, Bianco et al revealed that LRH-1 motifs were associated with the early stages of ovulation[29]. Liu et aldiscovered that LRH-1 is a critical upstream regulator of CYP19A1 gene expression in ovarian cells, which is essential in the formation of steroid hormines[14].…”

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confidence: 99%

LRH-1 high expression in the ovarian granulosa cells of PCOS patients

Yang

Wang

et al. 2021

Endocrine

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Purpose ： Polycystic ovary syndrome (PCOS) is considered as one of the most common endocrine disorder with heterogeneity. There are also reports that liver receptor homolog 1 [LRH-1 or nuclear receptor subfamily 5 group A member 2 (NR5A2)] plays an important role in the reproductive system. But up to now, there are no reports related to the link with PCOS and LRH-1. In this study, we aimed to detect the LRH-1 expression in the ovarian granulosa cell of PCOS patients and explore the potential relationship between LRH-1 and PCOS. Methods：146 follicular fluid sample were collected in this study, including 72 from PCOS patients and 74 from control patients who underwent intracytoplasmic sperm injection (ICSI) or in vitro fertilization-embryo transfer (IVF-ET). The ovarian granulosa cells were extracted from the patient's follicular fluid by magnetic-activated cell sorting (MACS) method, and the real-time quantitative PCR (qRT-PCR) was used to measure the expression of LRH-1 in ovarian granulosa cells. Then we analyzed the correlation between the expression level of LRH-1 and the clinical characteristics of patient by using Pearson Correlation analysis. Results：The expression of LRH-1 was significantly higher in PCOS patients ovarian granulosa cells than that in the control patients [vs(1.38±0.47)vs(1.03±0.32), t=5.327, p<0.0001], and it was positively correlated with antral follicles counting (AFC) (r=0.3607, p<0.0001)and the serum AMH(r=0.2662, p=0.0012)\LH(r=0.2518, p=0.0022)\T(r=0.2516, p=0.0022) in all patients. No statistical significance between LRH-1 and BMI, FSH, HOMA-IR, DHE-S, progesterone.Conclusions ： Compared with the control group, we found that LRH-1 was highly expressed in the ovarian granulosa cells of PCOS patients. Our study has revealed the relationship between the LRH-1 expression and PCOS, which suggested that LRH-1 may play an important role in ovulation disorders.While this finding provided new ideas for the study of the pathogenesis, it also provided a theoretical basis for the clinical diagnosis and treatment for PCOS.

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“…In this study, the methylation profiles of T A B L E 2 Percentages of morphologically intact, extruded, and degenerated follicles and antrum formation, mean (± SEM) follicular diameters and daily growth rate in vitro of caprine follicles. additional studies using ChIP-seq (Bianco et al, 2019;Mei et al, 2023;Nicol et al, 2018) approaches would be required.…”

Section: Ros Levels In the Spent Mediummentioning

confidence: 99%

Trimethylation profile of histones H3 lysine 4 and 9 in late preantral and early antral caprine follicles grown in vivo versus in vitro in the presence of anethole

Silva,

Morais,

Lima

et al. 2023

Molecular Reproduction Devel

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This study assessed the histones methylation profile (H3K4me3 and H3K9me3) in late preantral (PA) and early antral (EA) caprine follicles grown in vivo and in vitro, and the anethole effect during in vitro culture of PA follicles. Uncultured in vivo–grown follicles (PA, n = 64; EA, n = 73) were used as controls to assess the methylation profile and genes' expression related to apoptosis cascade (BAX, proapoptotic; BCL2, antiapoptotic), steroidogenesis (CYP17, CYP19A1), and demethylation (KDM1AX1, KDM1AX2, KDM3A). The isolated PA follicles (n = 174) were cultured in vitro for 6 days in α‐MEM+ in either absence (control) or presence of anethole. After culture, EA follicles were evaluated for methylation, mRNA abundance, and morphometry. Follicle diameter increased after culture, regardless of treatment. The methylation profile and the mRNA abundance were similar between in vivo–grown PA and EA follicles. Anethole treatment led to higher H3K4me3 fluorescence intensity in EA follicles. The mRNA abundances of BAX, CYP17, and CYP19A1 were higher, and BCL2 and KDM3A were lower in in vitro–grown EA follicles than in vivo–grown follicles. In conclusion, in vitro follicle culture affected H3K4me3 fluorescence intensity, mRNA abundance of apoptotic genes, and steroidogenic and demethylase enzymes compared with in vivo–grown follicles.

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The Ovulatory Signal Precipitates LRH-1 Transcriptional Switching Mediated by Differential Chromatin Accessibility

Cited by 25 publications

References 70 publications

Integrated Structural Modeling of Full-Length LRH-1 Reveals Inter-domain Interactions Contribute to Receptor Structure and Function

Integrated Structural Modeling of Full-Length LRH-1 Reveals Inter-domain Interactions Contribute to Receptor Structure and Function

LRH-1 high expression in the ovarian granulosa cells of PCOS patients

Trimethylation profile of histones H3 lysine 4 and 9 in late preantral and early antral caprine follicles grown in vivo versus in vitro in the presence of anethole

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