scholarly journals Genetics of premature ovarian insufficiency and the association with X-autosome translocations

Reproduction ◽  
2020 ◽  
Vol 160 (4) ◽  
pp. R55-R64
Author(s):  
Adriana Di-Battista ◽  
Mariana Moysés-Oliveira ◽  
Maria Isabel Melaragno
Keyword(s):  
X Chromosome ◽  
Molecular Mechanisms ◽  
Ovarian Function ◽  
Single Gene ◽  
Position Effect ◽  
Gene Mutations ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
Functional Consequences ◽  
Critical Regions

Premature ovarian insufficiency (POI) is the cessation of menstruation before the age of 40 and can result from different etiologies, including genetic, autoimmune, and iatrogenic. Of the genetic causes, single-gene mutations and cytogenetic alterations, such as X-chromosome aneuploidies and chromosome rearrangements, can be associated with POI. In this review, we summarize the genetic factors linked to POI and list the main candidate genes. We discuss the association of these genes with the ovarian development, the functional consequences of different mutational mechanisms and biological processes that are frequently disrupted during POI pathogenesis. Additionally, we focus on the high prevalence of X-autosome translocations involving the critical regions in Xq, known as POI1 and POI2, and discuss in depth the main hypotheses proposed to explain this association. Although the incorrect pairing of chromosomes during meiosis could lead to oocyte apoptosis, the reason for the prevalence of X-chromosome breakpoints at specific regions remains unclear. In most cases, studies on genes disrupted by balanced structural rearrangements cannot explain the ovarian failure. Thus, the position effect has emerged as a putative explanation for genetic mechanisms as translocations possibly result in changes in overall chromatin topology due to chromosome repositioning. Given the tremendous impact of POI on women’s quality of life, we highlight the value of investigations in to the interplay between ovarian function and gene regulation to deepen our understanding of the molecular mechanisms related to this disease, with the ultimate goal of improving patients’ care and assistance.

scholarly journals Meiotic Recombination Defects and Premature Ovarian Insufficiency

2021 ◽  
Vol 9 ◽  
Author(s):  
Chengzi Huang ◽  
Ting Guo ◽  
Yingying Qin
Keyword(s):  
Meiotic Recombination ◽  
Ovarian Function ◽  
Genetic Disorders ◽  
Gene Mutations ◽  
Strand Break ◽  
Premature Ovarian Insufficiency ◽  
Potential Candidate ◽  
Ovarian Insufficiency ◽  
Widespread Application ◽  
Individual Gene

Premature ovarian insufficiency (POI) is the depletion of ovarian function before 40 years of age due to insufficient oocyte formation or accelerated follicle atresia. Approximately 1–5% of women below 40 years old are affected by POI. The etiology of POI is heterogeneous, including genetic disorders, autoimmune diseases, infection, iatrogenic factors, and environmental toxins. Genetic factors account for 20–25% of patients. However, more than half of the patients were idiopathic. With the widespread application of next-generation sequencing (NGS), the genetic spectrum of POI has been expanded, especially the latest identification in meiosis and DNA repair-related genes. During meiotic prophase I, the key processes include DNA double-strand break (DSB) formation and subsequent homologous recombination (HR), which are essential for chromosome segregation at the first meiotic division and genome diversity of oocytes. Many animal models with defective meiotic recombination present with meiotic arrest, DSB accumulation, and oocyte apoptosis, which are similar to human POI phenotype. In the article, based on different stages of meiotic recombination, including DSB formation, DSB end processing, single-strand invasion, intermediate processing, recombination, and resolution and essential proteins involved in synaptonemal complex (SC), cohesion complex, and fanconi anemia (FA) pathway, we reviewed the individual gene mutations identified in POI patients and the potential candidate genes for POI pathogenesis, which will shed new light on the genetic architecture of POI and facilitate risk prediction, ovarian protection, and early intervention for POI women.

scholarly journals Long-term outcome of ovarian function in women with intermittent premature ovarian insufficiency

2016 ◽  
Vol 86 (2) ◽  
pp. 223-228 ◽  
Author(s):  
Anne Bachelot ◽  
Carole Nicolas ◽  
Maud Bidet ◽  
Jérôme Dulon ◽  
Monique Leban ◽  
...  
Keyword(s):  
Ovarian Function ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
Term Outcome ◽  
Long Term Outcome

scholarly journals Ayurveda management in premature ovarian insufficiency- A case study

2021 ◽  
Vol 5 (2) ◽  
pp. 49-56
Author(s):  
K P Vidya ◽  
Divya U ◽  
Sithara Satheesan
Keyword(s):  
Ovarian Function ◽  
Single Case ◽  
Hot Flashes ◽  
Signs And Symptoms ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
Post Evaluation ◽  
Related Quality ◽  
Health Related

Premature ovarian insufficiency (POI) is defined as a cessation of ovarian function before the age of 40 years. It is associated with hypoestrogenism and loss of residual follicles, both of which lead to menstrual abnormalities, pregnancy failures, and decreased health-related quality of life. The prevalence of POI is estimated at 1% in the general population. The risk of premature ovarian insufficiency (POI) before the age of 40 years is 1 %. The aetiopathology of premature ovarian insufficiency in the majority of cases is unknown and is termed as spontaneous or idiopathic POI. This is a case with signs and symptoms of POI which was developed after the administration of GnRH agonist drugs as a part of treatment of endometriosis. In this single case study, a female of 33 years having complaints of absence of periods since 6 months treated with Ayurveda treatment with pre and post evaluation. The symptoms of secondary amenorrhoea, hot flashes, vaginal dryness and mood swings were relieved after Ayurveda medications and procedures.

scholarly journals The Lighten up (Lip) gene of Drosophila melanogaster, a modifier of retroelement expression, position effect variegation and white locus insertion alleles.

Genetics ◽  
1994 ◽  
Vol 138 (1) ◽  
pp. 153-163 ◽  
Author(s):  
A K Csink ◽  
R Linsk ◽  
J A Birchler
Keyword(s):  
Drosophila Melanogaster ◽  
Single Gene ◽  
Position Effect ◽  
Gene Mutations ◽  
State Level ◽  
Transcript Abundance ◽  
Position Effect Variegation ◽  
Eye Color ◽  
Inverse Effect ◽  
Effect Variegation

Abstract We are interested in identifying single gene mutations that are involved in trans-acting dosage regulation in order to understand further the role of such genes in aneuploid syndromes, various types of dosage compensation as well as in regulatory mechanisms. The Lighten up (Lip) gene in Drosophila melanogaster was identified in a mutagenic screen to detect dominant second site modifiers of white-blood (wbl), a retrotransposon induced allele of the white eye color locus. Lip specifically enhances the phenotype of wbl as well as a subset of other retroelement insertion alleles of white, including the copia-induced allele, white-apricot (wa), and six alleles caused by insertion of I elements. We isolated six alleles of Lip which are all recessive lethal, although phenotypically additive heteroallelic escapers were recovered in some combinations. Lip also suppresses position effect variegation, indicating that it may have a role in chromatin configuration. Additionally, Lip modifies the total transcript abundance of both the blood and copia retrotransposons, having an inverse effect on the steady state level of blood transcripts, while showing a non-additive effect on copia RNA.

scholarly journals Premature Ovarian Insufficiency - an update on recent advances in understanding and management

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2069 ◽  
Author(s):  
Saioa Torrealday ◽  
Pinar Kodaman ◽  
Lubna Pal
Keyword(s):  
Ovarian Function ◽  
Clinical Medicine ◽  
Premature Ovarian Insufficiency ◽  
Clear Understanding ◽  
Timely Manner ◽  
Ovarian Insufficiency ◽  
Ongoing Research ◽  
Health Complications

Premature ovarian insufficiency is a complex and relatively poorly understood entity with a myriad of etiologies and multisystem sequelae that stem from premature deprivation of ovarian sex hormones. Timely diagnosis with a clear understanding of the various comorbidities that can arise from estrogen deficiency is vital to appropriately counsel and treat these patients. Prompt initiation of hormone therapy is critical to control the unsolicited menopausal symptoms that many women experience and to prevent long-term health complications. Despite ongoing efforts at improving our understanding of the mechanisms involved, any advancement in the field in recent decades has been modest at best and researchers remain thwarted by the complexity and heterogeneity of the underpinnings of this entity. In contrast, the practice of clinical medicine has made meaningful strides in providing assurance to the women with premature ovarian insufficiency that their quality of life as well as long-term health can be optimized through timely intervention. Ongoing research is clearly needed to allow pre-emptive identification of the at-risk population and to identify mechanisms that if addressed in a timely manner, can prolong ovarian function and physiology.

scholarly journals Elevated levels of miR-483-5p in oocytes aggravates premature ovarian insufficiency induced by CDDP by targeting the FKBP4

2020 ◽  
Author(s):  
huihui zhao ◽  
Wenqing Gu ◽  
Huogui Ouyang ◽  
Wenbin Pan ◽  
Hanbin Zhang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Sex Hormones ◽  
Ovarian Function ◽  
Target Prediction ◽  
Absolute Quantification ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
Real Time Quantitative Pcr ◽  
Quantification Analysis

Abstract Background Premature ovarian insufficiency (POI) is characterized by a loss of ovarian function before 40 years-of-age and represents a major cause of female infertility. POI is one of the dominant causes of cis-diaminedichloroplatinum (cisplatin, CDDP)-induced reproductive impairment. However, the detailed mechanisms underlying POI induced by CDDP remain unclear. Methods The POI C57B6/J mouse model was created by administering CDDP. The effects of FKBP4 were investigated using isobaric tags for relative and absolute quantification analysis (iTRAQ), real-time quantitative PCR (qRT-PCR) and western blotting. Target prediction was predicted using TargetScan software. Levels of sex hormones were tested using Enzyme-linked immunosorbent assays (ELISA). Results We found that the FKBP4 protein was down-regulated in the ovaries of CDDP model. Target prediction identified FKBP4 as a potential target for miR-483-5p , which was expressed at high levels in both the ovaries and serum of CDDP-POI mice, and in the serum from POI patients. In vitro experiments further confirmed that FKBP4 was the target for miR-483-5p in human cervical cancer cells (HeLa). The overexpression of FKBP4 in human granulosa cells (KGN) alleviated the apoptosis caused by CDDP and the overexpression of miR-483-5p . Furthermore, the overexpression of miR-483-5p in oocytes caused injury to the ovaries, and disrupted the levels of sex hormones in CDDP-POI mice (AMH: P <0.01; E 2 : P <0.01; FSH: P <0.01). Conclusions Analyses showed that miR-483-5p targets the FKBP4 protein in a mouse model of POI induced by CDDP. Elevated levels of miR-483-5p in oocytes aggravated POI induced by CDDP by targeting FKBP4. Overall, our data demonstrate that miR-483-5p was responsible for the underlying pathophysiology of POI induced by chemotherapeutic treatments, such as CDDP.

scholarly journals Elevated levels of miR-483-5p in oocytes aggravates premature ovarian insufficiency induced by CDDP by targeting the FKBP4

2020 ◽  
Author(s):  
huihui zhao ◽  
Wenqing Gu ◽  
Huogui Ouyang ◽  
Wenbin Pan ◽  
Hanbin Zhang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Sex Hormones ◽  
Ovarian Function ◽  
Target Prediction ◽  
Absolute Quantification ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
Real Time Quantitative Pcr ◽  
Quantification Analysis

Abstract Background: Premature ovarian insufficiency (POI) is characterized by a loss of ovarian function before 40 years-of-age and represents an existing challenge cause of female infertility. POI is one of the dominant causes of cis-diaminedichloroplatinum (cisplatin, CDDP)-induced reproductive impairment. However, the detailed mechanisms underlying POI induced by CDDP remain unclear.Methods: The POI C57B6/J mouse model was created by administering CDDP. The effects of FKBP4 were investigated using isobaric tags for relative and absolute quantification analysis (iTRAQ), real-time quantitative PCR (qRT-PCR) and western blotting. Target prediction was predicted using TargetScan software. Levels of sex hormones were tested using Enzyme-linked immunosorbent assays (ELISA).Results: We found that the FKBP4 protein was down-regulated in the ovaries of CDDP model. Target prediction identified FKBP4 as a potential target for miR-483-5p, which was expressed at high levels in both the ovaries and serum of CDDP-POI mice, and in the serum from POI patients. In vitro experiments further confirmed that FKBP4 was the target for miR-483-5p in human cervical cancer cells (HeLa). The overexpression of FKBP4 in human granulosa cells (KGN) alleviated the apoptosis caused by CDDP and the overexpression of miR-483-5p. Furthermore, the overexpression of miR-483-5p in oocytes caused injury to the ovaries, and disrupted the levels of sex hormones in CDDP-POI mice (AMH: P < 0.01; E2: P < 0.01; FSH: P < 0.01).Conclusions: Analyses showed that miR-483-5p targets the FKBP4 protein in a mouse model of POI induced by CDDP. Elevated levels of miR-483-5p in oocytes could aggravate POI induced by CDDP by targeting FKBP4. Overall, our data demonstrate that miR-483-5p was responsible for the underlying pathophysiology of POI induced by chemotherapeutic treatments, such as CDDP.

Premature ovarian insufficiency: Genetic causes and treatment options. A literature review

2021 ◽  
Vol 70 (3) ◽  
pp. 75-91
Author(s):  
Valentina M. Denisova ◽  
Maria I. Yarmolinskaya ◽  
Karina A. Zakurayeva
Keyword(s):  
Literature Review ◽  
Ovarian Function ◽  
Treatment Options ◽  
Clinical Signs ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
Diagnostic Features ◽  
Genetic Causes ◽  
Pubmed Database

Premature ovarian insufficiency is a syndrome characterized by hypergonadotropic ovarian insufficiency and the reduction of ovarian function before age 40. This leads to reproductive failures, metabolic changes, and a decrease in quality of life. Currently, occult and initial forms of premature ovarian insufficiency, which have their own diagnostic features and management tactics, can be figured out. The frequency of this syndrome is between 1.1 and 3.7% and the tendency for incidence to increase can be seen. This article is a literature review of the data available in the PubMed database (20052020), with international clinical guidelines taken into consideration. The genetic causes of premature ovarian insufficiency, clinical signs of this pathology and treatments options for such patients are included into the review. In addition, some features of assisted reproductive technology within this group are described.

FANCL gene mutations in premature ovarian insufficiency

2020 ◽  
Vol 41 (5) ◽  
pp. 1033-1041 ◽  
Author(s):  
Yajuan Yang ◽  
Ting Guo ◽  
Ran Liu ◽  
Hanni Ke ◽  
Weiwei Xu ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency
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