The role of ADAMTS4 and ADAMTS9 in cardiovascular disease in premature ovarian insufficiency and idiopathic hypogonadotropic hypogonadism

2018 ◽  
Vol 41 (12) ◽  
pp. 1477-1483 ◽  
Author(s):  
S. Ozler ◽  
E. Isci Bostanci ◽  
E. Oztas ◽  
M. Kuru Pekcan ◽  
B. Gumus Guler ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Hypogonadotropic Hypogonadism ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
Idiopathic Hypogonadotropic Hypogonadism

scholarly journals Long noncoding RNA HCP5 participates in premature ovarian insufficiency by transcriptionally regulating MSH5 and DNA damage repair via YB1

2020 ◽  
Vol 48 (8) ◽  
pp. 4480-4491 ◽  
Author(s):  
Xiaoyan Wang ◽  
Xinyue Zhang ◽  
Yujie Dang ◽  
Duan Li ◽  
Gang Lu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Noncoding Rna ◽  
Dna Damage Repair ◽  
Noncoding Rnas ◽  
Epigenetic Mechanism ◽  
Premature Ovarian Insufficiency ◽  
Genetic Etiology ◽  
Ovarian Insufficiency ◽  
Damage Repair

Abstract The genetic etiology of premature ovarian insufficiency (POI) has been well established to date, however, the role of long noncoding RNAs (lncRNAs) in POI is largely unknown. In this study, we identified a down-expressed lncRNA HCP5 in granulosa cells (GCs) from biochemical POI (bPOI) patients, which impaired DNA damage repair and promoted apoptosis of GCs. Mechanistically, we discovered that HCP5 stabilized the interaction between YB1 and its partner ILF2, which could mediate YB1 transferring into the nucleus of GCs. HCP5 silencing affected the localization of YB1 into nucleus and reduced the binding of YB1 to the promoter of MSH5 gene, thereby diminishing MSH5 expression. Taken together, we identified that the decreased expression of HCP5 in bPOI contributed to dysfunctional GCs by regulating MSH5 transcription and DNA damage repair via the interaction with YB1, providing a novel epigenetic mechanism for POI pathogenesis.

scholarly journals Premature Ovarian Insufficiency: New Perspectives on Genetic Cause and Phenotypic Spectrum

2016 ◽  
Vol 37 (6) ◽  
pp. 609-635 ◽  
Author(s):  
Elena J. Tucker ◽  
Sonia R. Grover ◽  
Anne Bachelot ◽  
Philippe Touraine ◽  
Andrew H. Sinclair
Keyword(s):  
Mouse Models ◽  
Genetic Basis ◽  
Current Knowledge ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Activity ◽  
Substantial Evidence ◽  
Ovarian Insufficiency ◽  
Phenotypic Spectrum ◽  
Disease Mechanisms

Abstract Premature ovarian insufficiency (POI) is one form of female infertility, defined by loss of ovarian activity before the age of 40 and characterized by amenorrhea (primary or secondary) with raised gonadotropins and low estradiol. POI affects up to one in 100 females, including one in 1000 before the age of 30. Substantial evidence suggests a genetic basis for POI; however, the majority of cases remain unexplained, indicating that genes likely to be associated with this condition are yet to be discovered. This review discusses the current knowledge of the genetic basis of POI. We highlight genes typically known to cause syndromic POI that can be responsible for isolated POI. The role of mouse models in understanding POI pathogenesis is discussed, and a thorough list of candidate POI genes is provided. Identifying a genetic basis for POI has multiple advantages, such as enabling the identification of presymptomatic family members who can be offered counseling and cryopreservation of eggs before depletion, enabling personalized treatment based on the cause of an individual's condition, and providing better understanding of disease mechanisms that ultimately aid the development of improved treatments.

Variants in Homologous Recombination Genes EXO1 and RAD51 Related with Premature Ovarian Insufficiency

2020 ◽  
Vol 105 (10) ◽  
pp. e3566-e3574
Author(s):  
Wei Luo ◽  
Ting Guo ◽  
Guangyu Li ◽  
Ran Liu ◽  
Shidou Zhao ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Budding Yeast ◽  
Protein Localization ◽  
Elevated Serum ◽  
Human Cell Line ◽  
Human Cells ◽  
Premature Ovarian Insufficiency ◽  
Primary Amenorrhea ◽  
Ovarian Insufficiency

Abstract Context Premature ovarian insufficiency (POI) is characterized by cessation of menstruation before 40 years of age and elevated serum level of FSH (>25 IU/L). Recent studies have found a few causative genes responsible for POI enriched in meiotic recombination and DNA damage repair pathways. Objective To investigate the role of variations in homologous recombination genes played in POI pathogenesis. Methods The whole exome sequencing was performed in 50 POI patients with primary amenorrhea. Functional characterizations of the novel variants were carried out in budding yeast and human cell line. Results We identified 8 missense variants in 7 homologous recombination genes, including EXO1, RAD51, RMI1, MSH5, MSH2, MSH6, and MLH1. The mutation p.Thr52Ser in EXO1 impaired the meiotic process of budding yeast and p.Glu68Gly in RAD51-altered protein localization in human cells, both of them impaired the efficiency of homologous recombination repair for DNA double-stranded breaks in human cells. Conclusions Our study first linked the variants of EXO1 and RAD51 with POI and further highlighted the role of DNA repair genes in ovarian dysgenesis.

Variations of C14ORF39 and SYCE1 identified in idiopathic premature ovarian insufficiency and nonobstructive azoospermia

2021 ◽  
Author(s):  
Dong Hou ◽  
Chencheng Yao ◽  
Bingying Xu ◽  
Wei Luo ◽  
Hanni Ke ◽  
...  
Keyword(s):  
Outcome Measure ◽  
Premature Ovarian Insufficiency ◽  
Functional Study ◽  
Nonobstructive Azoospermia ◽  
Ovarian Insufficiency ◽  
Functional Studies ◽  
Whole Exome ◽  
Inheritance Mode ◽  
Genetics And Genomics

Abstract Context Premature ovarian insufficiency (POI) and nonobstructive azoospermia (NOA) are the most sever disease causing irreversible infertility in female and male respectively. The contribution of synaptonemal complex (SC) genes variations in the pathogenesis of sporadic patients with POI and NOA has not been systematically illustrated. Objective To investigate the role of SC genes in the pathogenesis of sporadic POI and NOA. Design Genetic and functional study. Setting University-based reproductive medicine center. Patient(s) A total of 1,030 patients with sporadic POI and 400 patients with sporadic NOA. Intervention(s) The variations of SC genes were filtered in the in-house database of whole exome sequencing performed in 1,030 patients with sporadic POI and 400 patients with sporadic NOA. The pathogenic or likely pathogenic variations following recessive inheritance mode were selected according to American College of Medical Genetics and Genomics (ACMG) guidelines and confirmed by Sanger sequencing. The pathogenic effects of the variations were verified by functional studies. Main Outcome Measure(s) ACMG classification and functional characteristics. Result(s) Two homozygous variations of C14ORF39 and two recessive variations of SYCE1 were firstly identified in sporadic patients with POI and NOA respectively. Functional studies showed the C14ORF39 variations significantly accelerated the protein degradation, and the variations in SYCE1 disrupted its interaction with SYCP1 or C14ORF39, both of which affected SC assembly and meiosis. Conclusion(s) Our study identified novel pathogenic variations of C14ORF39 and SYCE1 in sporadic patients with POI or NOA, highlighting the essential role of SC genes in the maintenance of ovarian and testicular function.

scholarly journals Cardiovascular Disease Risk After Treatment-Induced Premature Ovarian Insufficiency in Female Survivors of Hodgkin Lymphoma

2018 ◽  
Vol 72 (25) ◽  
pp. 3374-3375
Author(s):  
Inge M. Krul ◽  
Annemieke W.J. Opstal–van Winden ◽  
Cécile P.M. Janus ◽  
Laurien A. Daniëls ◽  
Yolande Appelman ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Hodgkin Lymphoma ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
Female Survivors

Premature and Early Menopause in Relation to Cardiovascular Disease

2021 ◽  
Author(s):  
Izaäk Schipper ◽  
Yvonne V. Louwers
Keyword(s):  
Cardiovascular Disease ◽  
Postmenopausal Women ◽  
Cardiovascular Events ◽  
Premature Ovarian Insufficiency ◽  
Premature Menopause ◽  
Bilateral Oophorectomy ◽  
Early Menopause ◽  
Ovarian Insufficiency ◽  
Age At Menopause ◽  
Increased Risk

AbstractPostmenopausal women have an increased risk for cardiovascular diseases. It has been postulated that the loss of ovarian function and subsequent deficiency of endogenous estrogens after menopause contributes to this elevated risk of cardiovascular disease in postmenopausal women. Compared with woman entering menopause at the mean age of 51 years, in women with early menopause or premature ovarian insufficiency the risk for cardiovascular disease is even greater. These women lack the cardioprotective effect of endogenous estrogens for many more years than do women entering natural menopause. The majority of data assessing the risk of cardiovascular disease in relation to age at menopause and specifically premature menopause are derived from large epidemiological cohort studies. In addition, observations in women undergoing bilateral oophorectomy at an early age provide convincing evidence regarding association between early menopause or POI and the development of cardiovascular events and mortality. Moreover, genetic variants associated with earlier age at menopause have also been found to increase the risk of cardiovascular events in women. It has been substantiated that hormone replacement therapy (HRT) decreases the risk for ischemic heart disease and eliminates the increased cardiovascular disease mortality. It is therefore crucial to start HRT as soon as possible, particularly in women with premature ovarian insufficiency.

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