Dataset Information

Identification of a novel ESR1 mutation in a Chinese PCOS woman with estrogen insensitivity in IVF treatment.

ABSTRACT:

Background

Polycystic ovary syndrome (PCOS) is a complex reproductive disorder, that affects approximately 5-10% of women of reproductive age. The disease is complex because its evolution may be impacted by genetic, lifestyle and environmental factors. Previous studies have emphasized the important roles of estrogen receptors in the pathogenesis of PCOS.

Objective

To use whole exome sequencing (WES) to assess possible pathogenic factors in a PCOS patient who exhibited estrogen insensitivity during hormone replacement therapy (HRT) treatment.

Methods

Genome sequencing and variant filtering via WES were performed in a patient with PCOS. DNA extraction from 364 unrelated female controls without PCOS was followed by PCR amplification, Sanger sequencing and sequence alignment. Evolutionary conservation analysis, protein structural modelling and in silico prediction were applied to analyse the potential pathogenicity of the novel ESR1 mutation.

Result(s)

During the controlled ovarian hyperstimulation (COH) period of an IVF cycle, the patient experienced markedly prolonged ovarian stimulation due to a poor response to gonadotropins (Gn) and elevated serum FSH. A novel heterozygous ESR1 mutation, c.619G > A/p.A207T, leading to the replacement of a highly conserved alanine with a threonine, was identified in this patient, via WES analysis. This novel variant was not identified in 364 unrelated female controls without PCOS, or in the Exome Aggregation Consortium (ExAC) or 1000 Genome Project.

Conclusion(s)

We identified a novel heterozygous ESR1 mutation in a Han Chinese PCOS woman exhibiting clinical signs of estrogen insensitivity. This study may provide new strategies for IVF therapy, especially for patients who exhibit estrogen insensitivity during IVF cycle.

SUBMITTER: Liu F

PROVIDER: S-EPMC9673392 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Identification of a novel ESR1 mutation in a Chinese PCOS woman with estrogen insensitivity in IVF treatment.

Liu Faying F Tian Lifeng L Tan Jun J Li Zengming Z Qin Haiyan H Xu Dingfei D Huang Zhihui Z Wu Xingwu X Chen Ge G Wu Qiongfang Q Zou Yang Y

Reproductive biology and endocrinology : RB&E 20221118 1

<h4>Background</h4>Polycystic ovary syndrome (PCOS) is a complex reproductive disorder, that affects approximately 5-10% of women of reproductive age. The disease is complex because its evolution may be impacted by genetic, lifestyle and environmental factors. Previous studies have emphasized the important roles of estrogen receptors in the pathogenesis of PCOS.<h4>Objective</h4>To use whole exome sequencing (WES) to assess possible pathogenic factors in a PCOS patient who exhibited estrogen ins ...[more]

PMID: 36401248

Similar Datasets

Project description:BackgroundPolycystic ovary syndrome (PCOS) is the main cause of anovulatory infertility in women of reproductive age, and low-grade chronic inflammation plays a key role in the occurrence and development of PCOS. However, obesity, as a likely confounding factor, can affect the inflammatory state of PCOS patients.ObjectiveThe aim of this study was to comprehensively investigate intra-ovarian inflammatory states and their impact on embryo quality in PCOS patients with a normal BMI undergoing IVF treatment.MethodsDIA-mass spectrometry-based proteomics and bioinformatic analysis were combined to comprehensively profile the protein expression of granulosa cells (GCs) from 5 normal-BMI PCOS patients and 5 controls. Thirty-four cytokines were further systematically detected in follicular fluid (FF) from 32 age- and BMI-matched normal-BMI patients using Luminex liquid chip suspension technology. Next, the differentially expressed cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA) in 24 newly recruited subjects, and the relationship between these cytokines and embryo quality in PCOS patients was analysed. Finally, these cytokine levels were compared and evaluated in PCOS patients with different androgen levels.ResultsProteomic analysis showed that the suppression of substance metabolism and steroid biosynthesis, more interestingly, resulted in an enhanced immune and inflammatory response in the GCs of normal-BMI PCOS patients and prompted the involvement of cytokines in this process. Luminex analysis further showed that FF macrophage inflammatory protein-1 beta (MIP-1β) and stromal cell-derived factor-1 alpha (SDF-1α) levels were significantly increased in normal-BMI PCOS patients compared to controls (P = 0.005; P = 0.035, respectively), and the ELISA results were consistent with these findings. Besides, FF MIP-1β showed an inverse correlation with the number of D3 good-quality embryos and the good-quality blastocyst rate in patients with PCOS (P = 0.006; P = 0.003, respectively), which remained significant after correction for multiple comparisons. Moreover, SDF-1α levels had no relationship with embryo development in PCOS patients. Additionally, SDF-1α levels were significantly lower in PCOS patients with high androgen levels than in controls (P = 0.031).ConclusionsLocal ovarian inflammation was present in normal-BMI PCOS patients, affecting follicular development, and FF MIP-1β may be a potential biomarker associated with embryo quality in normal-BMI PCOS patients.

Project description:ContextOnly approximately 85% of patients with a clinical diagnosis complete androgen insensitivity syndrome and less than 30% with partial androgen insensitivity syndrome can be explained by inactivating mutations in the androgen receptor (AR) gene.ObjectiveThe objective of the study was to clarify this discrepancy by in vitro determination of AR transcriptional activity in individuals with disorders of sex development (DSD) and male controls.DesignQuantification of DHT-dependent transcriptional induction of the AR target gene apolipoprotein D (APOD) in cultured genital fibroblasts (GFs) (APOD assay) and next-generation sequencing of the complete coding and noncoding AR locus.SettingThe study was conducted at a university hospital endocrine research laboratory.PatientsGFs from 169 individuals were studied encompassing control males (n = 68), molecular defined DSD other than androgen insensitivity syndrome (AIS; n = 18), AR mutation-positive AIS (n = 37), and previously undiagnosed DSD including patients with a clinical suspicion of AIS (n = 46).Intervention(s)There were no interventions.Main outcome measure(s)DHT-dependent APOD expression in cultured GF and AR mutation status in 169 individuals was measured.ResultsThe APOD assay clearly separated control individuals (healthy males and molecular defined DSD patients other than AIS) from genetically proven AIS (cutoff < 2.3-fold APOD-induction; 100% sensitivity, 93.3% specificity, P < .0001). Of 46 DSD individuals with no AR mutation, 17 (37%) fell below the cutoff, indicating disrupted androgen signaling.ConclusionsAR mutation-positive AIS can be reliably identified by the APOD assay. Its combination with next-generation sequencing of the AR locus uncovered an AR mutation-negative, new class of androgen resistance, which we propose to name AIS type II. Our data support the existence of cellular components outside the AR affecting androgen signaling during sexual differentiation with high clinical relevance.

Dataset Information

Identification of a novel ESR1 mutation in a Chinese PCOS woman with estrogen insensitivity in IVF treatment.

Background

Objective

Methods

Result(s)

Conclusion(s)

Publications

Identification of a novel ESR1 mutation in a Chinese PCOS woman with estrogen insensitivity in IVF treatment.

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