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premature ovarian failure

I G Shestakova, V E Radzinsky, M B Khamoshina
Premature ovarian insufficiency (POI) is a life-changing diagnosis, with profound physical and psychological consequences. Despite the description of different genetic, immune and iatrogenic factors of POI, the etiology of most cases of this disease are unexplained, and optimal management strategies are still unclear. Recent data showed that POI may have a long period of oligomenorrhea before the fully developed form (complete ovarian failure stage), with the occurrence of amenorrhea and climacteric symptoms...
October 2016: Gynecological Endocrinology
Jane Stewart
Premature ovarian insufficiency (POI) has a reported prevalence of around 1% of the female population under the age of 40 years,(1) and is a diagnosis which carries huge implications for the woman's overall health and wellbeing, as well as her reproductive health and potential. These implications change as a woman's life-path proceeds and therefore this cannot ever be an isolated diagnosis at a single time point with a single best-fit treatment. Moreover, as Anne Bachelot's paper describes(2) , this is not a static and uniform condition...
October 18, 2016: Clinical Endocrinology
Ying Xiong, Te Liu, Suwei Wang, Huiying Chi, Chuan Chen, Jin Zheng
The dysfunction of ovarian granulosa cells (OGCs) directly affects the premature ovarian failure (POF). In vivo experiments showed that cyclophosphamide significantly induced mouse ovarian atrophy and proliferation inhibition of OGCs. The expressions of p53, p66Shc and p16 were significantly higher in OGCs of the cyclophosphamide treatment group. MTT assay showed that cyclophosphamide effectively inhibited the proliferation of OGCs in vitro. SA-β-Gal staining showed that the OGCs in the cyclophosphamide treatment group had many senescent cells...
October 8, 2016: Gene
Sylvie Jaillard, Linda Akloul, Marion Beaumont, Houda Hamdi-Roze, Christele Dubourg, Sylvie Odent, Solène Duros, Nathalie Dejucq-Rainsford, Marc-Antoine Belaud-Rotureau, Célia Ravel
BACKGROUND: Ovarian failure (OF) is considered premature if it occurs before the age of 40. This study investigates the genetic aetiology underlying OF in women under the age of 40 years. METHODS: We conducted an experimental prospective study performing all genome microarrays in 60 patients younger than 40 years presenting an OF revealed by a decrease of circulating Anti-Müllerian Hormone (AMH) and leading to an oocyte donation program. RESULTS: We identified nine significant copy number variations (CNVs) including candidate genes potentially implicated in reproductive function...
October 3, 2016: Journal of Ovarian Research
Iordan Stefanov Batchvarov, Rachel Williamson Taylor, Ximena Bustamante-Marín, Michael Czerwinski, Erika Segear Johnson, Sally Kornbluth, Blanche Capel
STUDY QUESTION: Can host fertility be rescued by grafting of a fragment of a healthy ovary soon after chemotherapy? SUMMARY ANSWER: We found that grafting a green fluorescent protein (GFP)-positive fragment from a healthy isogenic ovary to the left ovary of a chemo-treated host rescued function and fertility of the grafted host ovary, and resulted in the production of host-derived offspring as late as the sixth litter after chemotherapy (CTx) treatment, whereas none of the ungrafted controls produced a second litter...
October 3, 2016: Molecular Human Reproduction
Valerio Rossi, Monica Lispi, Salvatore Longobardi, Maurizio Mattei, Francesca Di Rella, Antonietta Salustri, Massimo De Felici, Francesca G Klinger
Premature ovarian failure and female infertility are frequent side effects of anticancer therapies, owing to the extreme sensitivity of the ovarian reserve oocytes to the damaging effects of irradiation and chemotherapy on DNA. We report here a robust protective effect of luteinizing hormone (LH) on the primordial follicle pool of prepubertal ovaries against the cisplatin (Cs)-induced apoptosis. In vitro LH treatment of prepubertal ovarian fragments generated anti-apoptotic signals by a subset of ovarian somatic cells expressing LH receptor (LHR) through cAMP/PKA and Akt pathways...
September 30, 2016: Cell Death and Differentiation
Christian Trolle, Morten Muhlig Nielsen, Anne Skakkebæk, Philippe Lamy, Søren Vang, Jakob Hedegaard, Iver Nordentoft, Torben Falck Ørntoft, Jakob Skou Pedersen, Claus Højbjerg Gravholt
Adults with 45,X monosomy (Turner syndrome) reflect a surviving minority since more than 99% of fetuses with 45,X monosomy die in utero. In adulthood 45,X monosomy is associated with increased morbidity and mortality, although strikingly heterogeneous with some individuals left untouched while others suffer from cardiovascular disease, autoimmune disease and infertility. The present study investigates the leukocyte DNAmethylation profile by using the 450K-Illumina Infinium assay and the leukocyte RNA-expression profile in 45,X monosomy compared with karyotypically normal female and male controls...
September 30, 2016: Scientific Reports
R T Ibitoye, S A Renowden, H J Faulkner, N J Scolding, C M Rice
Ovarioleukodystrophy-the co-occurrence of leukodystrophy and premature ovarian failure-is a rare presentation now recognised to be part of the clinical spectrum of vanishing white matter disease. We describe a woman with epilepsy and neuroimaging changes consistent with leukoencephalopathy who presented with non-convulsive status epilepticus after starting hormone replacement therapy in the context of premature ovarian failure. Genetic testing confirmed her to be a compound heterozygote for EIF2B5 mutations; the gene encodes a subunit of eukaryotic translation initiation factor 2B...
September 20, 2016: Practical Neurology
Xin He, Shu-Yu Wang, Cheng-Hong Yin, Tong Wang, Chan-Wei Jia, Yan-Min Ma
BACKGROUND: Premature ovarian failure (POF) is a disease that affects female fertility but has few effective treatments. Ovarian reserve function plays an important role in female fertility. Recent studies have reported that hydrogen can protect male fertility. Therefore, we explored the potential protective effect of hydrogen-rich water on ovarian reserve function through a mouse immune POF model. METHODS: To set up immune POF model, fifty female BALB/c mice were randomly divided into four groups: Control (mice consumed normal water, n = 10), hydrogen (mice consumed hydrogen-rich water, n = 10), model (mice were immunized with zona pellucida glycoprotein 3 [ZP3] and consumed normal water, n = 15), and model-hydrogen (mice were immunized with ZP3 and consumed hydrogen-rich water, n = 15) groups...
2016: Chinese Medical Journal
M F Garrido-Oyarzún, C Castelo-Branco
The increase in cancer incidence in younger people and the significant improvement in long and permanent remission have brought concern about their reproductive future and quality of life. Up to two-thirds of adult female patients undergoing chemotherapy for malignancies eventually develop premature ovarian failure. This condition is related to many complaints including vasomotor symptoms, osteoporosis, increased risk of cardiovascular diseases, sexual dysfunction, and infertility. Therefore, protection against iatrogenic infertility and loss of endocrine ovarian function caused by chemotherapy is currently of high priority...
September 17, 2016: Climacteric: the Journal of the International Menopause Society
Ting Zhang, Dawei Yan, Yang Yang, Aicui Ma, Lei Li, Zhonghui Wang, Qi Pan, Zuyue Sun
The objective of this study was to compare premature ovarian failure animal models established by several different source of inducers. Female ICR mice, KM mice, and SD rats were treated by cyclophosphamide at 120 mg/kg, busulfan at 12 mg/kg, cisplatin at 3 or 4 mg/kg, 4-vinylcyclohexene diepoxide at 160 mg/kg, 35% galactose food pellet, and tripterygium glycosides at 50 mg/kg, respectively. Parameters were analyzed by body weight, serum concentration level of related hormones, ovarian and uterine pathological examination...
September 7, 2016: Regulatory Toxicology and Pharmacology: RTP
P Grasa, S Sheikh, N Krzys, K Millar, S Janjua, P Nawaggi, S A Williams
Premature ovarian insufficiency (POI) occurs in 1% of reproductive-age women. The ovarian manifestation ranges from the presence of a variable population of follicles (follicular) to the absence of follicles (afollicular), and in the majority of cases the cause is unknown. A transgenic mouse model of follicular POI, the Double Mutant (DM), arises from oocyte-specific deletion of Mgat1 and C1galt1 required for the generation of O- and N-glycans. DM females are subfertile at 6 weeks, infertile by 9 weeks and exhibit POI by 12 weeks of age...
November 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
G Massenkeil, T Alexander, O Rosen, B Dörken, G Burmester, A Radbruch, F Hiepe, R Arnold
Issues of fertility and pregnancy require special attention in the long-term care of patients with autoimmune diseases (AD), who are candidates for haematopoietic stem cell transplantation (HSCT). In this single-centre observational study, we report fertility status and pregnancy outcomes in 15 patients (11 female and 4 male) after immunoablation with cyclophosphamide, antithymocyte globulin and autologous CD34(+)-selected HSCT for severe, refractory AD. The median follow-up after HSCT was 12 years (range 2-16 years)...
November 2016: Rheumatology International
Joop S E Laven
Primary ovarian insufficiency (POI), also known as premature ovarian failure or premature menopause, is defined as cessation of menstruation before the expected age of menopause. Potential etiologies for POI can be divided into genetic, autoimmune, and iatrogenic categories. This review will try to summarize the genetic basis of POI focusing on recent data that are available using newer genetic techniques such as genome-wide association studies, whole-exome sequencing (WES), or next-generation sequencing techniques...
July 2016: Seminars in Reproductive Medicine
Hatice Duygu Saatcioglu, Ileana Cuevas, Diego H Castrillon
In mammals, females are born with finite numbers of oocytes stockpiled as primordial follicles. Oocytes are "reawakened" via an ovarian-intrinsic process that initiates their growth. The forkhead transcription factor Foxo3 controls reawakening downstream of PI3K-AKT signaling. However, the identity of the presumptive upstream cell surface receptor controlling the PI3K-AKT-Foxo3 axis has been questioned. Here we show that the receptor tyrosine kinase Kit controls reawakening. Oocyte-specific expression of a novel constitutively-active KitD818V allele resulted in female sterility and ovarian failure due to global oocyte reawakening...
August 2016: PLoS Genetics
Te Liu, Suwei Wang, Qiong Li, Yongyi Huang, Chuan Chen, Jin Zheng
Premature ovarian failure (POF) refers to the presence of ovarian atrophic permanent amenorrhea in women under the age of 40. The pathogenesis of POF remains to be fully elucidated. Telocytes are a group of specialized cells with a small cell volume and very long cytoplasmic prolongations with dichotomous branching. Previous studies have indicated that telocytes function to support the trachea and serve as stem cell niches. Although it has been confirmed that telocytes are present in numerous organs in mammals, it remains to be determined whether they are present in ovarian tissues and whether they are involved in the development of POF...
September 2016: Molecular Medicine Reports
Kun-Kun Song, Wen-Wen Ma, Cong Huang, Jia-Hui Ding, Dan-Dan Cui, Xiu-Juan Tan, Jing Xiao, Ming-Min Zhang
The aim of the present study was to explore the effect and mechanism of Bushen Huoxue recipe (BHR) on ovarian reserve in mice with premature ovarian failure (POF). Mice were divided into 3 groups: normal group, model group and BHR group. Intraperitoneal injection of cyclophosphamide was performed to create the POF model. Primordial follicular (PDF) number, ovarian wet weight, ovarian index, and estrous cycle were analyzed to evaluate the effect of BHR on POF. Meanwhile, the mRNA and protein level of Mouse Vasa Homologue (MVH) in the bone marrow, peripheral blood and ovary were detected, to explore the underlying mechanism of the treatment efficacy of BHR on ovarian reserve...
August 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
Helena C Fabbri, Juliana G Ribeiro de Andrade, Andréa T Maciel-Guerra, Gil Guerra-Júnior, Maricilda P de Mello
Mutations in the NR5A1 gene, which encodes the steroidogenic factor 1 (SF1), are responsible for different phenotypes of disorders of sex development (DSD), such as bilateral anorchia and hypospadias. Furthermore, they can be associated with primary amenorrhea, premature ovarian failure, male infertility, adrenal tumors, and endometriosis. Direct sequencing of the 7 NR5A1 exons including ∼1,000 bp of the 5'-upstream and 3'-downstream regions and all intron-exon boundaries was performed in patients with DSD...
2016: Sexual Development: Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation
Hala Gabr, Moshira Abdelhakiim Rateb, Maha Hamdi El Sissy, Hanan Ahmed Seddiek, Sarah Ali Abdelhameed Gouda
OBJECTIVES: Chemotherapy targets rapidly dividing tissues in the body. It destroys the progenitor cells in gonads resulting in premature ovarian failure. Studies have suggested that bone marrow-derived stem cells can generate oocytes in chemotherapy treated female rats after transplantation. The present study aimed to assess mechanism of homing, the action of injected BM-MSCs on ovarian function after ovarian damage. EXPERIMENTAL DESIGN: Seventy two female albino rats were randomly allocated into Control and CTX group, The Experimental protocol was lasted for 12 weeks during which serum FSH and E2 were monitored twice at the end of the 2nd week (12 rats) and 8th week (6 rats)...
October 2016: Microscopy Research and Technique
Hanyong Jin, Miae Won, Si Eun Park, Seunghwa Lee, Mira Park, Jeehyeon Bae
Anti-Müllerian hormone (AMH) is required for proper sexual differentiation by regulating the regression of the Müllerian ducts in males. Recent studies indicate that AMH could be an important factor for maintaining the ovarian reserve. However, the mechanisms of AMH regulation in the ovary are largely unknown. Here, we provide evidence that AMH is an ovarian target gene of steroidogenic factor-1 (SF-1), an orphan nuclear receptor required for proper follicle development. FOXL2 is an evolutionally conserved transcription factor, and its mutations cause blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES), wherein affected females display eyelid defects and premature ovarian failure (POF)...
2016: PloS One
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