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Sample records for aged mammalian ovaries

  1. Reproductive age-associated fibrosis in the stroma of the mammalian ovary.

    PubMed

    Briley, Shawn M; Jasti, Susmita; McCracken, Jennifer M; Hornick, Jessica E; Fegley, Barbara; Pritchard, Michele T; Duncan, Francesca E

    2016-09-01

    Under normal physiological conditions, tissue remodeling in response to injury leads to tissue regeneration without permanent damage. However, if homeostasis between synthesis and degradation of extracellular matrix (ECM) components is altered, fibrosis - or the excess accumulation of ECM - can disrupt tissue architecture and function. Several organs, including the heart, lung and kidney, exhibit age-associated fibrosis. Here we investigated whether fibrosis underlies aging in the ovary - an organ that ages chronologically before other organs. We used Picrosirius Red (PSR), a connective tissue stain specific for collagen I and III fibers, to evaluate ovarian fibrosis. Using bright-field, epifluorescence, confocal and polarized light microscopy, we validated the specific staining of highly ordered PSR-stained fibers in the ovary. We next examined ovarian PSR staining in two mouse strains (CD1 and CB6F1) across an aging continuum and found that PSR staining was minimal in ovaries from reproductively young adult animals, increased in distinct foci in animals of mid-to-advanced reproductive age, and was prominent throughout the stroma of the oldest animals. Consistent with fibrosis, there was a reproductive age-associated increase in ovarian hydroxyproline content. We also observed a unique population of multinucleated macrophage giant cells, which are associated with chronic inflammation, within the ovarian stroma exclusively in reproductively old mice. In fact, several genes central to inflammation had significantly higher levels of expression in ovaries from reproductively old mice relative to young mice. These results establish fibrosis as an early hallmark of the aging ovarian stroma, and this altered microenvironment may contribute to the age-associated decline in gamete quality. PMID:27491879

  2. The Mammalian Ovary from Genesis to Revelation

    PubMed Central

    Edson, Mark A.; Nagaraja, Ankur K.; Matzuk, Martin M.

    2009-01-01

    Two major functions of the mammalian ovary are the production of germ cells (oocytes), which allow continuation of the species, and the generation of bioactive molecules, primarily steroids (mainly estrogens and progestins) and peptide growth factors, which are critical for ovarian function, regulation of the hypothalamic-pituitary-ovarian axis, and development of secondary sex characteristics. The female germline is created during embryogenesis when the precursors of primordial germ cells differentiate from somatic lineages of the embryo and take a unique route to reach the urogenital ridge. This undifferentiated gonad will differentiate along a female pathway, and the newly formed oocytes will proliferate and subsequently enter meiosis. At this point, the oocyte has two alternative fates: die, a common destiny of millions of oocytes, or be fertilized, a fate of at most approximately 100 oocytes, depending on the species. At every step from germline development and ovary formation to oogenesis and ovarian development and differentiation, there are coordinated interactions of hundreds of proteins and small RNAs. These studies have helped reproductive biologists to understand not only the normal functioning of the ovary but also the pathophysiology and genetics of diseases such as infertility and ovarian cancer. Over the last two decades, parallel progress has been made in the assisted reproductive technology clinic including better hormonal preparations, prenatal genetic testing, and optimal oocyte and embryo analysis and cryopreservation. Clearly, we have learned much about the mammalian ovary and manipulating its most important cargo, the oocyte, since the birth of Louise Brown over 30 yr ago. PMID:19776209

  3. MAMMALIAN APOPTOSIS IN WHOLE NEONATAL OVARIES USING CONFOCAL LASER SCANNING MICROSCOPY

    EPA Science Inventory

    MAMMALIAN APOPTOSIS IN WHOLE NEONATAL OVARIES USING CONFOCAL LASER SCANNING MICROSCOPY

    Robert M. Zucker Susan C. Jeffery and Sally D. Perreault

    Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Prot...

  4. Expression of DMRT1 in the mammalian ovary and testis--from marsupials to mice.

    PubMed

    Pask, A J; Behringer, R R; Renfree, M B

    2003-01-01

    Doublesex and mab3 related transcript (DMRT1) was identified as a candidate gene for human 9p24.3 associated sex reversal. DMRT1 orthologues have highly conserved roles in sexual differentiation from flies and worms to humans. A DMRT1 orthologue was isolated from a marsupial, the tammar wallaby Macropus eugenii. The wallaby gene is highly conserved with other vertebrate DMRT1 genes, especially within the P/S and DM domains. It is expressed in the differentiating testis from the late fetus, during pouch life and in the adult. As in eutherian mammals, DMRT1 protein was localized in the germ cells and the Sertoli cells of the testis, but in addition it was detected in the Leydig cells, peri-tubular myoid cells and within the acrosome of the sperm heads. DMRT1 protein was also detected in the fetal and adult ovary pre-granulosa, granulosa and germ cells. Similarly, we also detected DMRT1 in the granulosa cells of all developing follicles in the adult mouse ovary. This is the first report of DMRT1 expression in the adult mammalian ovary, and suggests a wider role for this gene in mammals, in both the testis and ovarian function. PMID:14684988

  5. TrkB receptors are required for follicular growth and oocyte survival in the mammalian ovary

    PubMed Central

    Paredes, Alfonso; Romero, Carmen; Dissen, Gregory A.; DeChiara, Tom M.; Reichardt, Louis; Cornea, Anda; Ojeda, Sergio R.; Xu, Baoji

    2009-01-01

    Although it is well established that both follicular assembly and the initiation of follicle growth in the mammalian ovary occur independently of pituitary hormone support, the factors controlling these processes remain poorly understood. We now report that neurotrophins (NTs) signaling via TrkB receptors are required for the growth of newly formed follicles. Both neurotrophin-4/5 (NT-4) and brain-derived neurotrophic factor (BDNF), the preferred TrkB ligands, are expressed in the infantile mouse ovary. Initially, they are present in oocytes, but this site of expression switches to granulosa cells after the newly assembled primordial follicles develop into growing primary follicles. Full-length kinase domain-containing TrkB receptors are expressed at low and seemingly unchanging levels in the oocytes and granulosa cells of both primordial and growing follicles. In contrast, a truncated TrkB isoform lacking the intracellular domain of the receptor is selectively expressed in oocytes, where it is targeted to the cell membrane as primary follicles initiate growth. Using gene-targeted mice lacking all TrkB isoforms, we show that the ovaries of these mice or those lacking both NT-4 and BDNF suffer a stage-selective deficiency in early follicular development that compromises the ability of follicles to grow beyond the primary stage. Proliferation of granulosa cells— required for this transition—and expression of FSH receptors (FSHR), which reflects the degree of biochemical differentiation of growing follicles, are reduced in trkB-null mice. Ovaries from these animals grafted under the kidney capsule of wild-type mice fail to sustain follicular growth and show a striking loss of follicular organization, preceded by massive oocyte death. These results indicate that TrkB receptors are required for the early growth of ovarian follicles and that they exert this function by primarily supporting oocyte development as well as providing granulosa cells with a proliferative

  6. The ageing ovary and uterus: new biological insights

    PubMed Central

    Nelson, S.M.; Telfer, E.E.; Anderson, R.A.

    2013-01-01

    BACKGROUND Advanced maternal age is associated with reduced fertility and adverse pregnancy outcomes. This review details recent developments in our understanding of the biology and mechanisms underlying reproductive ageing in women and the implications for fertility and pregnancy. METHODS Sociological online libraries (IBSS, SocINDEX), PubMed and Google Scholar were searched for relevant demographic, epidemiological, clinical and biological studies, using key words and hierarchical MeSH terms. From this, we identified and focused on key topics where it was judged that there had been clinically relevant advances in the understanding of ovarian and uterine ageing with implications for improved diagnostics and novel interventions. RESULTS Mapping of the ovarian reserve, follicular dynamics and associated biomarkers, across the reproductive lifespan has recently been performed. This now allows an assessment of the effects of environmental, lifestyle and prenatal exposures on follicular dynamics and the identification of their impact during periods of germ cell vulnerability and may also facilitate early identification of individuals with shorter reproductive lifespans. If women choose to time their family based on their ovarian reserve this would redefine the meaning of family planning. Despite recent reports of the potential existence of stem cells which may be used to restore the primordial follicle and thereby the oocyte pool, therapeutic interventions in female reproductive ageing at present remain limited. Maternal ageing has detrimental effects on decidual and placental development, which may be related to repeated exposure to sex steroids and underlie the association of ageing with adverse perinatal outcomes. CONCLUSIONS Ageing has incontrovertible detrimental effects on the ovary and the uterus. Our enhanced understanding of ovarian ageing will facilitate early identification of individuals at greatest risk, and novel therapeutic interventions. Changes in both

  7. Novel Action of FSH on Stem Cells in Adult Mammalian Ovary Induces Postnatal Oogenesis and Primordial Follicle Assembly.

    PubMed

    Bhartiya, Deepa; Parte, Seema; Patel, Hiren; Sriraman, Kalpana; Zaveri, Kusum; Hinduja, Indira

    2016-01-01

    Adult mammalian ovary has been under the scanner for more than a decade now since it was proposed to harbor stem cells that undergo postnatal oogenesis during reproductive period like spermatogenesis in testis. Stem cells are located in the ovary surface epithelium and exist in adult and menopausal ovary as well as in ovary with premature failure. Stem cells comprise two distinct populations including spherical, very small embryonic-like stem cells (VSELs which express nuclear OCT-4 and other pluripotent and primordial germ cells specific markers) and slightly bigger ovarian germ stem cells (OGSCs with cytoplasmic OCT-4 which are equivalent to spermatogonial stem cells in the testes). These stem cells have the ability to spontaneously differentiate into oocyte-like structures in vitro and on exposure to a younger healthy niche. Bone marrow may be an alternative source of these stem cells. The stem cells express FSHR and respond to FSH by undergoing self-renewal, clonal expansion, and initiating neo-oogenesis and primordial follicle assembly. VSELs are relatively quiescent and were recently reported to survive chemotherapy and initiate oogenesis in mice when exposed to FSH. This emerging understanding and further research in the field will help evolving novel strategies to manage ovarian pathologies and also towards oncofertility. PMID:26635884

  8. Novel Action of FSH on Stem Cells in Adult Mammalian Ovary Induces Postnatal Oogenesis and Primordial Follicle Assembly

    PubMed Central

    Bhartiya, Deepa; Parte, Seema; Patel, Hiren; Sriraman, Kalpana; Zaveri, Kusum; Hinduja, Indira

    2016-01-01

    Adult mammalian ovary has been under the scanner for more than a decade now since it was proposed to harbor stem cells that undergo postnatal oogenesis during reproductive period like spermatogenesis in testis. Stem cells are located in the ovary surface epithelium and exist in adult and menopausal ovary as well as in ovary with premature failure. Stem cells comprise two distinct populations including spherical, very small embryonic-like stem cells (VSELs which express nuclear OCT-4 and other pluripotent and primordial germ cells specific markers) and slightly bigger ovarian germ stem cells (OGSCs with cytoplasmic OCT-4 which are equivalent to spermatogonial stem cells in the testes). These stem cells have the ability to spontaneously differentiate into oocyte-like structures in vitro and on exposure to a younger healthy niche. Bone marrow may be an alternative source of these stem cells. The stem cells express FSHR and respond to FSH by undergoing self-renewal, clonal expansion, and initiating neo-oogenesis and primordial follicle assembly. VSELs are relatively quiescent and were recently reported to survive chemotherapy and initiate oogenesis in mice when exposed to FSH. This emerging understanding and further research in the field will help evolving novel strategies to manage ovarian pathologies and also towards oncofertility. PMID:26635884

  9. Female Reproductive Aging Is Master-Planned at the Level of Ovary

    PubMed Central

    Banerjee, Sayani; Banerjee, Sutapa; Saraswat, Ghungroo; Bandyopadhyay, Soma Aditya; Kabir, Syed N.

    2014-01-01

    The ovary receives a finite pool of follicles during fetal life. Atresia remains the major form of follicular expenditure at all stages since development of ovary. The follicular reserve, however, declines at an exponential rate leading to accelerated rate of decay during the years preceding menopause. We examined if diminished follicle reserve that characterizes ovarian aging impacts the attrition rate. Premature ovarian aging was induced in rats by intra-embryonic injection of galactosyltransferase-antibody on embryonic day 10. On post-natal day 35 of the female litters, either a wedge of fat (sham control) or a wild type ovary collected from 25-day old control rats, was transplanted under the ovarian bursa in both sides. Follicular growth and atresia, and ovarian microenvironment were evaluated in the follicle-deficient host ovary and transplanted ovary by real time RT-PCR analysis of growth differentiation factor-9, bone morphogenetic protein 15, and kit ligand, biochemical evaluation of ovarian lipid peroxidation, superoxide dismutase (SOD) and catalase activity, and western blot analysis of ovarian pro- and anti-apoptotic factors including p53, bax, bcl2, and caspase 3. Results demonstrated that the rate of follicular atresia, which was highly preponderant in the follicle-deficient ovary of the sham-operated group, was significantly prevented in the presence of the transplanted ovary. As against the follicle-deficient ovary of the sham-operated group, the follicle-deficient host ovary as well as the transplanted ovary in the ovary-transplanted group exhibited stimulated follicle growth with increased expression of anti-apoptotic factors and down regulation of pro-apoptotic factors. Both the host and transplanted ovaries also had significantly lower rate of lipid peroxidation with increased SOD and catalase activity. We conclude that the declining follicular reserve is perhaps the immediate thrust that increases the rate of follicle depletion during the final

  10. Molecular aging of the mammalian vestibular system.

    PubMed

    Brosel, Sonja; Laub, Christoph; Averdam, Anne; Bender, Andreas; Elstner, Matthias

    2016-03-01

    Dizziness and imbalance frequently affect the elderly and contribute to falls and frailty. In many geriatric patients, clinical testing uncovers a dysfunction of the vestibular system, but no specific etiology can be identified. Neuropathological studies have demonstrated age-related degeneration of peripheral and central vestibular neurons, but the molecular mechanisms are poorly understood. In contrast, recent studies into age-related hearing loss strongly implicate mitochondrial dysfunction, oxidative stress and apoptotic cell death of cochlear hair cells. While some data suggest that analogous biological pathomechanisms may underlie vestibular dysfunction, actual proof is missing. In this review, we summarize the available data on the molecular causes of vestibular dysfunction. PMID:26739358

  11. Aging and the Mammalian Regulatory Triumvirate

    PubMed Central

    Rollo, C. David

    2010-01-01

    A temporal framework linking circadian rhythms and clocks to aging rates identifies a specific window of target of rapamycin (TOR) signaling associated with growth hormone (GH) and insulin-like growth factor (IGF-1) (largely exclusive of insulin) in early sleep. IGF-1 signaling is released by growth hormone secretory peaks and downregulation of IGF-1 binding protein-1 resulting in activation of the mitogen activated protein kinase/extracellular signal response kinase (MAPK/ERK) and phosphoinositide 3-kinase-protein kinase B (PI3K-PKB/Akt) signaling pathways. Phosphorylation of Akt activates TOR which mediates the protein synthesis and growth functions of the GH axis. TOR activity is also associated with downregulated stress resistance, faster aging and reduced lifespan. IGF-1 signaling is terminated by falling GH and upregulation of IGF-1 binding proteins mediated by somatostatin and rising corticosteroids in later sleep. This suppresses PI3K-Akt signaling, thus activating the forkhead transcription factors (FOXOs) and stress-resistance pathways involved in promoting longevity. Thus, sleep appears to encompass both pathways currently identified as most relevant to aging and they toggle successively on the phosphorylation status of Akt. I propose a modified version of Pearl’s rate of living theory emphasizing the hard-wired antagonism of growth (TOR) and stress resistance (FOXO). The sleep association of TOR and FOXO in temporally separated windows and their sequential temporal deployment may change much of the way we think about aging and how to manipulate it. PMID:22396860

  12. Crowding and Follicular Fate: Spatial Determinants of Follicular Reserve and Activation of Follicular Growth in the Mammalian Ovary

    PubMed Central

    Gaytan, Francisco; Morales, Concepcion; Leon, Silvia; Garcia-Galiano, David; Roa, Juan; Tena-Sempere, Manuel

    2015-01-01

    Initiation of growth of resting ovarian follicles is a key phenomenon for providing an adequate number of mature oocytes in each ovulation, while preventing premature exhaustion of primordial follicle reserve during the reproductive lifespan. Resting follicle dynamics strongly suggest that primordial follicles are under constant inhibitory influences, by mechanisms and factors whose nature remains ill defined. In this work, we aimed to assess the influence of spatial determinants, with special attention to clustering patterns and crowding, on the fate of early follicles in the adult mouse and human ovary. To this end, detailed histological and morphometric analyses, targeting resting and early growing follicles, were conducted in ovaries from mice, either wild type (WT) or genetically modified to lack kisspeptin receptor expression (Kiss1r KO), and healthy adult women. Kiss1r KO mice were studied as model of persistent hypogonadotropism and anovulation. Different qualitative and quantitative indices of the patterns of spatial distribution of resting and early growing follicles in the mouse and human ovary, including the Morisita’s index of clustering, were obtained. Our results show that resting primordial follicles display a clear-cut clustered pattern of spatial distribution in adult mouse and human ovaries, and that resting follicle aggrupation is inversely correlated with the proportion of follicles initiating growth and entering into the growing pool. As a whole, our data suggest that resting follicle crowding, defined by changes in density and clustered pattern of distribution, is a major determinant of follicular activation and the fate of ovarian reserve. Uneven follicle crowding would constitute the structural counterpart of the major humoral regulators of early follicular growth, with potential implications in ovarian ageing and pathophysiology. PMID:26642206

  13. Age-Specific Gene Expression Profiles of Rhesus Monkey Ovaries Detected by Microarray Analysis.

    PubMed

    Wei, Hengxi; Liu, Xiangjie; Yuan, Jihong; Li, Li; Zhang, Dongdong; Guo, Xinzheng; Liu, Lin; Zhang, Shouquan

    2015-01-01

    The biological function of human ovaries declines with age. To identify the potential molecular changes in ovarian aging, we performed genome-wide gene expression analysis by microarray of ovaries from young, middle-aged, and old rhesus monkeys. Microarray data was validated by quantitative real-time PCR. Results showed that a total of 503 (60 upregulated, 443 downregulated) and 84 (downregulated) genes were differentially expressed in old ovaries compared to young and middle-aged groups, respectively. No difference in gene expression was found between middle-aged and young groups. Differentially expressed genes were mainly enriched in cell and organelle, cellular and physiological process, binding, and catalytic activity. These genes were primarily associated with KEGG pathways of cell cycle, DNA replication and repair, oocyte meiosis and maturation, MAPK, TGF-beta, and p53 signaling pathway. Genes upregulated were involved in aging, defense response, oxidation reduction, and negative regulation of cellular process; genes downregulated have functions in reproduction, cell cycle, DNA and RNA process, macromolecular complex assembly, and positive regulation of macromolecule metabolic process. These findings show that monkey ovary undergoes substantial change in global transcription with age. Gene expression profiles are useful in understanding the mechanisms underlying ovarian aging and age-associated infertility in primates. PMID:26421297

  14. Age-Specific Gene Expression Profiles of Rhesus Monkey Ovaries Detected by Microarray Analysis

    PubMed Central

    Wei, Hengxi; Liu, Xiangjie; Yuan, Jihong; Li, Li; Zhang, Dongdong; Guo, Xinzheng; Liu, Lin; Zhang, Shouquan

    2015-01-01

    The biological function of human ovaries declines with age. To identify the potential molecular changes in ovarian aging, we performed genome-wide gene expression analysis by microarray of ovaries from young, middle-aged, and old rhesus monkeys. Microarray data was validated by quantitative real-time PCR. Results showed that a total of 503 (60 upregulated, 443 downregulated) and 84 (downregulated) genes were differentially expressed in old ovaries compared to young and middle-aged groups, respectively. No difference in gene expression was found between middle-aged and young groups. Differentially expressed genes were mainly enriched in cell and organelle, cellular and physiological process, binding, and catalytic activity. These genes were primarily associated with KEGG pathways of cell cycle, DNA replication and repair, oocyte meiosis and maturation, MAPK, TGF-beta, and p53 signaling pathway. Genes upregulated were involved in aging, defense response, oxidation reduction, and negative regulation of cellular process; genes downregulated have functions in reproduction, cell cycle, DNA and RNA process, macromolecular complex assembly, and positive regulation of macromolecule metabolic process. These findings show that monkey ovary undergoes substantial change in global transcription with age. Gene expression profiles are useful in understanding the mechanisms underlying ovarian aging and age-associated infertility in primates. PMID:26421297

  15. Predicting age of ovarian failure after radiation to a field that includes the ovaries

    SciTech Connect

    Wallace, W. Hamish B. . E-mail: Hamish.Wallace@ed.ac.uk; Thomson, Angela B.; Saran, Frank; Kelsey, Tom W.

    2005-07-01

    Purpose: To predict the age at which ovarian failure is likely to develop after radiation to a field that includes the ovary in women treated for cancer. Methods and Materials: Modern computed tomography radiotherapy planning allows determination of the effective dose of radiation received by the ovaries. Together with our recent assessment of the radiosensitivity of the human oocyte, the effective surviving fraction of primordial oocytes can be determined and the age of ovarian failure, with 95% confidence limits, predicted for any given dose of radiotherapy. Results: The effective sterilizing dose (ESD: dose of fractionated radiotherapy [Gy] at which premature ovarian failure occurs immediately after treatment in 97.5% of patients) decreases with increasing age at treatment. ESD at birth is 20.3 Gy; at 10 years 18.4 Gy, at 20 years 16.5 Gy, and at 30 years 14.3 Gy. We have calculated 95% confidence limits for age at premature ovarian failure for estimated radiation doses to the ovary from 1 Gy to the ESD from birth to 50 years. Conclusions: We report the first model to reliably predict the age of ovarian failure after treatment with a known dose of radiotherapy. Clinical application of this model will enable physicians to counsel women on their reproductive potential following successful treatment.

  16. Active zones of mammalian neuromuscular junctions: formation, density, and aging

    PubMed Central

    Nishimune, Hiroshi

    2012-01-01

    Presynaptic active zones are synaptic vesicle release sites that playessential roles in the function and pathology of mammalian neuromuscular junctions (NMJs). The molecular mechanisms of active zone organization utilize presynaptic voltage-dependent calcium channels (VDCCs) in NMJs as scaffolding proteins. VDCCs interact extracellularly with the muscle-derived synapse organizer, laminin β2, and interact intracellularly with active zone-specific proteins, such as Bassoon, CAST/Erc2/ELKS2alpha, ELKS, Piccolo, and RIMs. These molecular mechanisms are supported by studies in P/Q- and N-type VDCCs double-knockout mice, and they are consistent with the pathological conditions of Lambert-Eaton myasthenic syndrome and Pierson syndrome, which are caused by autoantibodies against VDCCs or by a laminin β2 mutation. During normal postnatal maturation, NMJs maintain the density of active zones, while NMJs triple their size. However, active zones become impaired during aging. Propitiously, muscle exercise ameliorates the active zone impairment in aged NMJs, which suggests the potential for therapeutic strategies. PMID:23252894

  17. Ovarian aging-like phenotype in the hyperandrogenism-induced murine model of polycystic ovary.

    PubMed

    Rezvanfar, Mohammad Amin; Shojaei Saadi, Habib A; Gooshe, Maziar; Abdolghaffari, Amir Hosein; Baeeri, Maryam; Abdollahi, Mohammad

    2014-01-01

    There are prominently similar symptoms, effectors, and commonalities in the majority of characteristics between ovarian aging and polycystic ovarian syndrome (PCOS). Despite the approved role of oxidative stress in the pathogenesis of PCOS and aging, to our knowledge, the link between the PCO(S) and aging has not been investigated yet. In this study we investigated the possible exhibition of ovarian aging phenotype in murine model of PCO induced by daily oral administration of letrozole (1 mg/kg body weight) for 21 consecutive days in the female Wistar rats. Hyperandrogenization showed irregular cycles and histopathological characteristics of PCO which was associated with a significant increase in lipid peroxidation (LPO) and reactive oxygen species (ROS) and decrease in total antioxidant capacity (TAC) in serum and ovary. Moreover, serum testosterone, insulin and tumor necrosis factor-alpha (TNF-α) levels, and ovarian matrix metalloproteinase-2 (MMP-2) were increased in PCO rats compared with healthy controls, while estradiol and progesterone diminished. Almost all of these findings are interestingly found to be common with the characteristics identified with (ovarian) aging showing that hyperandrogenism-induced PCO in rat is associated with ovarian aging-like phenotypes. To our knowledge, this is the first report that provides evidence regarding the phenomenon of aging in PCO. PMID:24693338

  18. Ovarian Aging-Like Phenotype in the Hyperandrogenism-Induced Murine Model of Polycystic Ovary

    PubMed Central

    Rezvanfar, Mohammad Amin; Shojaei Saadi, Habib A.; Gooshe, Maziar; Abdolghaffari, Amir Hosein; Baeeri, Maryam; Abdollahi, Mohammad

    2014-01-01

    There are prominently similar symptoms, effectors, and commonalities in the majority of characteristics between ovarian aging and polycystic ovarian syndrome (PCOS). Despite the approved role of oxidative stress in the pathogenesis of PCOS and aging, to our knowledge, the link between the PCO(S) and aging has not been investigated yet. In this study we investigated the possible exhibition of ovarian aging phenotype in murine model of PCO induced by daily oral administration of letrozole (1 mg/kg body weight) for 21 consecutive days in the female Wistar rats. Hyperandrogenization showed irregular cycles and histopathological characteristics of PCO which was associated with a significant increase in lipid peroxidation (LPO) and reactive oxygen species (ROS) and decrease in total antioxidant capacity (TAC) in serum and ovary. Moreover, serum testosterone, insulin and tumor necrosis factor-alpha (TNF-α) levels, and ovarian matrix metalloproteinase-2 (MMP-2) were increased in PCO rats compared with healthy controls, while estradiol and progesterone diminished. Almost all of these findings are interestingly found to be common with the characteristics identified with (ovarian) aging showing that hyperandrogenism-induced PCO in rat is associated with ovarian aging-like phenotypes. To our knowledge, this is the first report that provides evidence regarding the phenomenon of aging in PCO. PMID:24693338

  19. Effect of body mass index and age on in vitro fertilization in polycystic ovary syndrome

    PubMed Central

    Kalem, Müberra Namlı; Kalem, Ziya; Sarı, Tamer; Ateş, Can; Gürgan, Timur

    2016-01-01

    Objective The aim of this study was to investigate age-related variations in the effect of body mass index (BMI) on in vitro fertilization (IVF) outcomes. Material and Methods This was a cohort study conducted by retrospectively investigating the IVF cycles of 653 polycystic ovary syndrome (PCOS) patients under the age of 40 years who were diagnosed based on the Rotterdam criteria in a private IVF clinic between 2005 and 2015. The study included data from 653 IVF cycles of PCOS patients. The patients were classified into three groups based on their BMI, i.e., normal weight (n=299), overweight (n=208), and obese (n=146). The patients were also grouped by age: 562 patients were under the age of 35 years and 91 patients were above the age of 35 years. Then, BMI- and age-related variations in the IVF cycle parameters and clinical pregnancy rates of patients with PCOS were investigated. The Mantel–Haenszel Chi-square statistical assessment method was used to determine whether the effect of BMI on IVF outcomes varies with age. Results Variations in cycle variables with BMI and age showed that IVF cycles were negatively affected by increases in obesity and age. Clinical pregnancy rates were found to be lower in the obese group than in the other groups, particularly in the age group above 35 years; however, this difference could not be proven statistically. Conclusion The present study evaluated obesity and clinical pregnancy rates in IVF cycles in PCOS patients according to age groups, and particularly in the obese group, the clinical pregnancy rates were observed to be lower in the age group ≥35 years than in the other BMI groups; however, this difference was found to be statistically insignificant. PMID:27403074

  20. Chronic exposures to low levels of estradiol and their effects on the ovaries and reproductive hormones: Comparison with aging

    PubMed Central

    Gilbreath, Ebony T.; MohanKumar, Sheba M.J.; Balasubramanian, Priya; Agnew, Dalen W.; MohanKumar, P.S.

    2015-01-01

    Aging in female rats is characterized by a state called “constant estrous” in which rats are unable to ovulate, have polycystic ovaries and moderately elevated estrogen levels. We hypothesized that chronic exposure of young animals to low levels of E2 can produce reproductive changes similar to that seen in aging animals. Adult female rats were sham-implanted (control) or implanted with slow-release E2 (20 ng/day) pellets for 30, 60, or 90 days. Old constant estrous (OCE) rats were used for comparison. Estrous cyclicity was monitored periodically. At the end of treatment, animals were sacrificed, trunk blood was collected for hormone measurements and ovaries for immunohistochemistry. Young animals became acyclic with increasing duration of E2 exposure while OCE rats were in a state of acyclicity. Ovaries became increasingly more cystic with E2 exposure, and were comparable to OCE rats; however, there was a marked reduction in interstitial tissue with exogenous E2 treatment. Exogenous E2 also decreased Mullerian inhibiting substance expression, increased infiltration of macrophages without much impact on apoptosis in the ovaries. Serum testosterone levels decreased in E2-treated young animals, while it increased significantly in OCE rats. There was a marked reduction in LH but not FSH levels with E2 exposure in both young and old animals. These results indicate that even very low doses of E2 are capable of inducing aging-like changes in young animals. PMID:26779558

  1. Polycystic Ovary Syndrome: Important Underrecognised Cardiometabolic Risk Factor in Reproductive-Age Women

    PubMed Central

    Baldani, Dinka Pavicic; Skrgatic, Lana; Ougouag, Roya

    2015-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age. Although PCOS is diagnosed exclusively based on reproductive criteria, it is also a metabolic disorder. Insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, obesity, and dyslipidemia are more common in women with PCOS than in age-comparable women without PCOS. Many of the metabolic abnormalities that manifest in PCOS are worsened by the concurrent incidence of obesity. However, some of these metabolic perturbations occur even in lean women with PCOS and therefore are rightfully recognized as intrinsic to PCOS. The intrinsic factors that produce these metabolic disturbances are reviewed in this paper. The consequences of obesity and the other metabolic aberrations are also discussed. The metabolic perturbations in PCOS patients lead to chronic low-grade inflammation and to cardiovascular impairments that heighten the risk of having cardiovascular disease. Even though many studies have shown an elevation in surrogate biomarkers of cardiovascular disease in PCOS women, it is still not clear to what extent and magnitude the elevation precipitates more frequent and earlier events. PMID:26124830

  2. Expression of preproenkephalin-like mRNA and its peptide products in mammalian testis and ovary.

    PubMed Central

    Kilpatrick, D L; Howells, R D; Noe, M; Bailey, L C; Udenfriend, S

    1985-01-01

    The distribution of preproenkephalin mRNA and proenkephalin-derived peptides have been examined in gonadal tissues from rats, hamsters, and cattle. A preproenkephalin mRNA band was detected in the ovaries of all three species and in hamster testis that is identical in size to the 1450-nucleotide mRNA typically found in tissues that express proenkephalin. Rat testis, on the other hand, expresses at least one preproenkephalin-like mRNA that is substantially greater in size (1900 nucleotides). [Met]enkephalin-containing peptides were also detected in each of the gonadal tissues examined. Although the abundance of preproenkephalin-like mRNA in rat testis was comparable to that in rat brain, the testicular content of proenkephalin-derived [Met]enkephalin sequences was less than 4% of the rat brain content. Together these data suggest that preproenkephalin-like mRNA in rat testis is not efficiently translated, proenkephalin-derived peptides undergo rapid turnover in this tissue, or the mRNA in rat testis has a frameshift resulting in an altered coding sequence. Images PMID:3864164

  3. Aging influences steroid hormone release by mink ovaries and their response to leptin and IGF-I

    PubMed Central

    Sirotkin, Alexander V.; Mertin, Dušan; Süvegová, Karin; Harrath, Abdel Halim; Kotwica, Jan

    2016-01-01

    ABSTRACT The aim of our study was to understand whether ovarian steroid hormones, and their response to the metabolic hormones leptin and IGF-I leptin, could be involved in the control of mink reproductive aging via changes in basal release of ovarian progesterone and estradiol. For this purpose, we compared the release of progesterone and estradiol by ovarian fragments isolated from young (yearlings) and old (3-5 years of age) minks cultured with and without leptin and IGF-I (0, 1, 10 or 100 ng/ml). We observed that isolated ovaries of older animals produced less progesterone but not less estradiol than the ovaries of young animals. Leptin addition stimulated estradiol release by the ovarian tissue of young animals but inhibited it in older females. Leptin did not influence progesterone output by the ovaries of either young or older animals. IGF-I inhibited estradiol output in young but not old animals, whereas progesterone release was inhibited by IGF-I irrespective of the animal age. Our observations demonstrate the involvement of both leptin and IGF-I in the control of mink ovarian steroid hormones release. Furthermore, our findings suggest that reproductive aging in minks can be due to (a) reduction in basal progesterone release and (b) alterations in the response of estradiol but not of progesterone to leptin and IGF-I. PMID:26794607

  4. The impact of Quaternary Ice Ages on mammalian evolution.

    PubMed Central

    Lister, Adrian M

    2004-01-01

    The Quaternary was a time of extensive evolution among mammals. Most living species arose at this time, and many of them show adaptations to peculiarly Quaternary environments. The latter include continental northern steppe and tundra, and the formation of lakes and offshore islands. Although some species evolved fixed adaptations to specialist habitats, others developed flexible adaptations enabling them to inhabit broad niches and to survive major environmental changes. Adaptation to short-term (migratory and seasonal) habitat change probably played a part in pre-adapting mammal species to the longer-term cyclical changes of the Quaternary. Fossil evidence indicates that environmental changes of the order of thousands of years have been sufficient to produce subspeciation, but speciation has typically required one hundred thousand to a few hundred thousand years, although there are both shorter and longer exceptions. The persistence of taxa in environments imposing strong selective regimes may have been important in forcing major adaptive change. Individual Milankovitch cycles are not necessarily implicated in this process, but nor did they generally inhibit evolutionary change among mammals: many evolutionary divergences built over multiple climatic cycles. Deduction of speciation timing requires input from fossils and modern phenotypic and breeding data, to complement and constrain mitochondrial DNA coalescence dates which appear commonly to overestimate taxic divergence dates and durations of speciation. Migrational and evolutionary responses to climate change are not mutually exclusive but, on the contrary, may be synergistic. Finally, preliminary analysis suggests that faunal turnover, including an important element of speciation, was elevated in the Quaternary compared with the Neogene, at least in some biomes. Macroevolutionary species selection or sorting has apparently resulted in a modern mammalian fauna enriched with fast-reproducing and/or adaptively

  5. Melanin-based coloration covaries with ovary size in an age-specific manner in the barn owl

    NASA Astrophysics Data System (ADS)

    Roulin, Alexandre

    2009-10-01

    While the adaptive function of black eumelanin-based coloration is relatively well known, the function of reddish-brown pheomelanin-based coloration is still unclear. Only a few studies have shown or suggested that the degree of reddish-brownness is associated with predator-prey relationships, reproductive parameters, growth rate and immunity. To gain insight into the physiological correlates of melanin-based coloration, I collected barn owl ( Tyto alba) cadavers and examined the covariation between this colour trait and ovary size, an organ that increases in size before reproduction. A relationship is expected because melanin-based coloration often covaries with sexual activity. The results showed that reddish-brown juveniles had larger ovaries than whiter juveniles particularly in individuals in poor condition and outside the breeding season, while in birds older than 2 years lightly coloured females had larger ovaries than reddish-brown conspecifics. As barn owls become less reddish-brown between the first and second year of age, the present study suggests that reddish-brown pheomelanic and whitish colorations are associated with juvenile- and adult-specific adaptations, respectively.

  6. Identification of differentially expressed genes in ovaries of chicken attaining sexual maturity at different ages.

    PubMed

    Kang, Li; Zhang, Yujie; Zhang, Ningbo; Zang, Li; Wang, Meng; Cui, Xinxing; Jiang, Yunliang

    2012-03-01

    In poultry as well as in other birds, sexual maturity is one of the important factors influencing female reproduction and egg production. In this study, cDNA-amplified fragment length polymorphism (cDNA-AFLP) differential display approach was used to identify genes related to sexual maturity. Using 54 EcoR I/Mse I selective primer combinations, totally 403 differentially expressed transcript-derived fragments (TDFs) were isolated, 27 of which belong to 25 unigenes. By real-time quantitative PCR (qPCR), the expression pattern of 13 genes was confirmed; among them, four genes including ZNF183 (P < 0.01), KIAA0700, CCT6A, and 23e 15 (P < 0.05) are significantly up-regulated and one gene (Loc418883) is significantly down-regulated (P < 0.01) in sexually mature ovaries compared to immature ones. The mRNA expression dynamics of ZNF183, CCT6A, 23e 15 and Loc418883 were further investigated in ovaries of 70-, 300- and 500-day-old commercial egg-laying hens: the expression level of CCT6A was the highest in 300-day-old hens (P < 0.05), while that of Loc418883 in 500-day-old hens was significantly higher than the other two stages (P < 0.01). The expression levels of ZNF183 and 23e 15 in ovary increase significantly from 70-day-old hens (P < 0.01) and 300-day-old (P < 0.05) to 500-day-old hens, respectively. The consistence of CCT6A expression and egg-laying performance suggests that CCT6A likely plays important role in sexual maturity in hens. PMID:21691707

  7. Sirtuins and the Estrogen Receptor as Regulators of the Mammalian Mitochondrial UPR in Cancer and Aging.

    PubMed

    Germain, D

    2016-01-01

    By being both the source of ATP and the mediator of apoptosis, the mitochondria are key regulators of cellular life and death. Not surprisingly alterations in the biology of the mitochondria have implications in a wide array of diseases including cancer and age-related diseases such as neurodegeneration. To protect the mitochondria against damage the mitochondrial unfolded protein response (UPR(mt)) orchestrates several pathways, including the protein quality controls, the antioxidant machinery, oxidative phosphorylation, mitophagy, and mitochondrial biogenesis. While several reports have implicated an array of transcription factors in the UPR(mt), most of the focus has been on studies of Caenorhabditis elegans, which led to the identification of ATFS-1, for which the mammalian homolog remains unknown. Meanwhile, there are studies which link the UPR(mt) to sirtuins and transcription factors of the Foxo family in both C. elegans and mammalian cells but those have been largely overlooked. This review aims at emphasizing the potential importance of these studies by building on the large body of literature supporting the key role of the sirtuins in the maintenance of the integrity of the mitochondria in both cancer and aging. Further, the estrogen receptor alpha (ERα) and beta (ERβ) are known to confer protection against mitochondrial stress, and at least ERα has been linked to the UPR(mt). Considering the difference in gender longevity, this chapter also includes a discussion of the link between the ERα and ERβ and the mitochondria in cancer and aging. PMID:27037754

  8. Gene variants associated with age at menopause are also associated with polycystic ovary syndrome, gonadotrophins and ovarian volume

    PubMed Central

    Saxena, R.; Bjonnes, A.C.; Georgopoulos, N.A.; Koika, V.; Panidis, D.; Welt, C.K.

    2015-01-01

    STUDY QUESTION Is there a relationship between the genetic risk for polycystic ovary syndrome (PCOS) and genetic variants that influence timing of menopause? SUMMARY ANSWER The genetic risk score, which sums the contribution of variants at all menopause loci, was associated with PCOS. WHAT IS ALREADY KNOWN Ovarian parameters and anti-Mullerian hormone levels suggest that women with PCOS should have a later age at menopause. STUDY DESIGN, SIZE, DURATION The study was a case–control examination of genetic variants associated with age at menopause in a discovery cohort of women with PCOS (n = 485) and controls (n = 407) from Boston recruited from 2003 to 2012. Replication was performed in women from Greece (cases, n = 884 and controls, n = 311). PARTICIPANTS/MATERIALS, SETTINGS, METHODS PCOS was defined by the National Institutes of Health criteria in Boston and Greece (n = 783), with additional subjects fulfilling the Rotterdam criteria (hyperandrogenism, polycystic ovary morphology and regular menses) in Greece (n = 101). Controls in Boston and Greece had regular menstrual cycles and no hyperandrogenism. Allele frequencies for variants previously associated with age at menopause were examined in PCOS cases and controls, along with the relationship to quantitative traits. MAIN RESULTS AND ROLE OF CHANCE The variant rs11668344-G was associated with decreased risk of PCOS (odds ratio: 0.77 [0.59–0.93]; P = 0.004). There was a strong relationship between the late menopause allele rs12294104-T and increased LH levels (β ± SE; 0.26 ± 0.06; P = 5.2 × 10−5) and the LH:FSH ratio (0.28 ± 0.06; P = 2.7 × 10−6). The minor allele at rs10852344-T was associated with smaller ovarian volume (−0.16 ± 0.05; P = 0.0012). A genetic risk score calculated from 16 independent variants associated with age at menopause was also associated with PCOS (P < 0.02), LH and the LH:FSH ratio (both P < 0.05). LIMITATIONS, REASONS FOR CAUTION The variant rs11668344 was not associated

  9. Subclinical lumbar polyradiculopathy, polyneuritis and ganglionitis in aged wild and exotic mammalians.

    PubMed

    Anderson, W I; Cummings, J F; Steinberg, H; deLahunta, A; King, J M

    1993-07-01

    Subclinical lumbar polyradiculopathy was present in the intradural dorsal and ventral nerve rootlets of 19 aged individuals of the following wild and exotic mammalian species: woodrat, raccoon, mink, lynx, reindeer, red deer, musk ox, scimitar-horned oryx, Arabian oryx, hybrid waterbuck, Persian onager, Przewalski's wild horse, Malayan sun bear, Asian elephant, East African river hippopotamus, vervet monkey and rhesus monkey. It was characterized by mild to severe multifocal ballooning of myelin sheaths. Occasionally, ballooned myelin sheaths contained thin strands of myelin and macrophages surrounding distorted axons. Additionally, a mild incidental lymphocytic polyneuritis was present in intradural nerve rootlets of the Malayan sun bear, and a moderate lymphocytic spinal ganglionitis in the East African river hippopotamus. PMID:8408784

  10. A new method for estimating species age supports the coexistence of malaria parasites and their Mammalian hosts.

    PubMed

    Silva, Joana C; Egan, Amy; Arze, Cesar; Spouge, John L; Harris, David G

    2015-05-01

    Species in the genus Plasmodium cause malaria in humans and infect a variety of mammals and other vertebrates. Currently, estimated ages for several mammalian Plasmodium parasites differ by as much as one order of magnitude, an inaccuracy that frustrates reliable estimation of evolutionary rates of disease-related traits. We developed a novel statistical approach to dating the relative age of evolutionary lineages, based on Total Least Squares regression. We validated this lineage dating approach by applying it to the genus Drosophila. Using data from the Drosophila 12 Genomes project, our approach accurately reconstructs the age of well-established Drosophila clades, including the speciation event that led to the subgenera Drosophila and Sophophora, and age of the melanogaster species subgroup. We applied this approach to hundreds of loci from seven mammalian Plasmodium species. We demonstrate the existence of a molecular clock specific to individual Plasmodium proteins, and estimate the relative age of mammalian-infecting Plasmodium. These analyses indicate that: 1) the split between the human parasite Plasmodium vivax and P. knowlesi, from Old World monkeys, occurred 6.1 times earlier than that between P. falciparum and P. reichenowi, parasites of humans and chimpanzees, respectively; and 2) mammalian Plasmodium parasites originated 22 times earlier than the split between P. falciparum and P. reichenowi. Calibrating the absolute divergence times for Plasmodium with eukaryotic substitution rates, we show that the split between P. falciparum and P. reichenowi occurred 3.0-5.5 Ma, and that mammalian Plasmodium parasites originated over 64 Ma. Our results indicate that mammalian-infecting Plasmodium evolved contemporaneously with their hosts, with little evidence for parasite host-switching on an evolutionary scale, and provide a solid timeframe within which to place the evolution of new Plasmodium species. PMID:25589738

  11. A New Method for Estimating Species Age Supports the Coexistence of Malaria Parasites and Their Mammalian Hosts

    PubMed Central

    Silva, Joana C.; Egan, Amy; Arze, Cesar; Spouge, John L.; Harris, David G.

    2015-01-01

    Species in the genus Plasmodium cause malaria in humans and infect a variety of mammals and other vertebrates. Currently, estimated ages for several mammalian Plasmodium parasites differ by as much as one order of magnitude, an inaccuracy that frustrates reliable estimation of evolutionary rates of disease-related traits. We developed a novel statistical approach to dating the relative age of evolutionary lineages, based on Total Least Squares regression. We validated this lineage dating approach by applying it to the genus Drosophila. Using data from the Drosophila 12 Genomes project, our approach accurately reconstructs the age of well-established Drosophila clades, including the speciation event that led to the subgenera Drosophila and Sophophora, and age of the melanogaster species subgroup. We applied this approach to hundreds of loci from seven mammalian Plasmodium species. We demonstrate the existence of a molecular clock specific to individual Plasmodium proteins, and estimate the relative age of mammalian-infecting Plasmodium. These analyses indicate that: 1) the split between the human parasite Plasmodium vivax and P. knowlesi, from Old World monkeys, occurred 6.1 times earlier than that between P. falciparum and P. reichenowi, parasites of humans and chimpanzees, respectively; and 2) mammalian Plasmodium parasites originated 22 times earlier than the split between P. falciparum and P. reichenowi. Calibrating the absolute divergence times for Plasmodium with eukaryotic substitution rates, we show that the split between P. falciparum and P. reichenowi occurred 3.0–5.5 Ma, and that mammalian Plasmodium parasites originated over 64 Ma. Our results indicate that mammalian-infecting Plasmodium evolved contemporaneously with their hosts, with little evidence for parasite host-switching on an evolutionary scale, and provide a solid timeframe within which to place the evolution of new Plasmodium species. PMID:25589738

  12. Dual inhibition of phosphatidylinositol 3'-kinase and mammalian target of rapamycin using NVP-BEZ235 as a novel therapeutic approach for mucinous adenocarcinoma of the ovary.

    PubMed

    Kudoh, Akiko; Oishi, Tetsuro; Itamochi, Hiroaki; Sato, Seiya; Naniwa, Jun; Sato, Shinya; Shimada, Muneaki; Kigawa, Junzo; Harada, Tasuku

    2014-03-01

    Ovarian mucinous adenocarcinoma (MAC) resists standard chemotherapy and is associated with poor prognosis. A more effective treatment is needed urgently. The present study assessed the possibility of molecular-targeted therapy with a novel dual inhibitor of phosphatidylinositol 3'-kinase (PI3K) and mammalian target of rapamycin (mTOR), NVP-BEZ235 (BEZ235) to treat of MAC. Seven human MAC cell lines were used in this study. The sensitivity of the cells to BEZ235, temsirolimus, and anticancer agents was determined with the WST-8 assay. Cell cycle distribution was assessed by flow cytometry, and the expression of proteins in apoptotic pathways and molecules of the PI3K/Akt/mTOR signaling pathways was determined by Western blot analysis. We also examined the effects of BEZ235 on tumor growth in nude mice xenograft models. The cell lines showed half-maximal inhibitory concentration values of BEZ235 from 13 to 328 nmol/L. Low half-maximal inhibitory concentration values to BEZ235 were observed in MCAS and OMC-1 cells; these 2 lines have an activating mutation in the PIK3CA gene. NVP-BEZ235 down-regulated the protein expression of phosphorylated (p-) Akt, p-p70S6K, and p-4E-BP1, suppressed cell cycle progression, up-regulated the expression of cleaved PARP and cleaved caspase 9, and increased apoptotic cells. Synergistic effects were observed on more than 5 cell lines when BEZ235 was combined with paclitaxel or cisplatin. The treatment of mice bearing OMC-1 or RMUG-S with BEZ235 significantly suppressed tumor growth in MAC xenograft models without severe weight loss. We conclude that the PI3K/Akt/mTOR pathway is a potential therapeutic target and that BEZ235 should be explored as a therapeutic agent for MAC. PMID:24552895

  13. Microbial-mammalian co-metabolites dominate the age-associated urinary metabolic phenotype in Taiwanese and American Populations

    PubMed Central

    Swann, Jonathan R.; Spagou, Konstantina; Lewis, Matthew; Nicholson, Jeremy K.; Glei, Dana A.; Seeman, Teresa E.; Coe, Christopher L.; Goldman, Noreen; Ryff, Carol D.; Weinstein, Maxine; Holmes, Elaine

    2013-01-01

    Understanding the metabolic processes associated with aging is key to developing effective management and treatment strategies for age-related diseases. We investigated the metabolic profiles associated with age in a Taiwanese and an American population. 1H NMR spectral profiles were generated for urine specimens collected from the Taiwanese Social Environment and Biomarkers of Aging Study (SEBAS; n= 857; age 54-91 years) and the Mid-Life in the USA study (MIDUS II; n= 1148; age 35-86 years). Multivariate and univariate linear projection methods revealed some common age-related characteristics in urinary metabolite profiles in the American and Taiwanese populations, as well as some distinctive features. In both cases, two metabolites--4-cresyl sulfate (4CS) and phenylacetylglutamine (PAG)—were positively associated with age. In addition, creatine and β-hydroxy-β-methylbutyrate (HMB) were negatively correlated with age in both populations (p<4×10-6). These age-associated gradients in creatine and HMB reflect decreasing muscle mass with age. The systematic increase in PAG and 4CS was confirmed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Both are products of concerted microbial-mammalian host co-metabolism and indicate an age-related association with the balance of host-microbiome metabolism. PMID:23701591

  14. Assay of SF/sub 6/ and spark-decomposed SF/sub 6/ for mutagenic activity in the CHO/HGPRT (Chinese hamster ovary/hypoxanthine-guanine phosphoribosyl transferase) mammalian cell system

    SciTech Connect

    Kurka, K.; Griffin, G.D.

    1987-01-01

    The potential mutagenic (and cytotoxic) activity of SF/sub 6/ and spark-decomposed SF/sub 6/ was investigated in an in vitro mammalian cell culture system using Chinese Hamster Ovary (CHO) cells. The CHO cells were exposed to the gases in vacutainer tubes which were constantly rotated. After a 4 h exposure the mutagenic and cytotoxic activity was assayed with the CHO/hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT) system. Results indicated that SF/sub 6/ was neither cytotoxic nor mutagenic to CHO cells. Spark-decomposed SF/sub 6/ was found to be strongly cytotoxic (-80% cell death following 4 h exposure to 2 kJ spark discharge in 60 cm/sup 3/ at 1000 torr of SF/sub 6/) but not mutagenic. Increasing spark energy increased cytotoxicity but the spark samples remained nonmutagenic. The CHO/HGPRT system was coupled with a metabolic activation (S9 fraction) system used for detecting promutagens. When exposures were carried out in the presence of S9 fraction, SF/sub 6/ was still neither cytotoxic nor mutagenic; spark-decomposed SF/sub 6/ was again strongly cytotoxic but not mutagenic. It appears that SF/sub 6/ and sparked SF/sub 6/ are neither promutagens nor direct acting mutagens in the CHO/HGPRT system. Studies have begun using a more mutagenically sensitive subclone of the CHO cells known as CHO-AS/sub 52/. The results of initial experiments using the CHO-AS/sub 52/ cells remain unchanged. 9 refs., 1 tab.

  15. Evidence for an Age-Dependent Decline in Axon Regeneration in the Adult Mammalian Central Nervous System.

    PubMed

    Geoffroy, Cédric G; Hilton, Brett J; Tetzlaff, Wolfram; Zheng, Binhai

    2016-04-12

    How aging impacts axon regeneration after CNS injury is not known. We assessed the impact of age on axon regeneration induced by Pten deletion in corticospinal and rubrospinal neurons, two neuronal populations with distinct innate regenerative abilities. As in young mice, Pten deletion in older mice remains effective in preventing axotomy-induced decline in neuron-intrinsic growth state, as assessed by mTOR activity, neuronal soma size, and axonal growth proximal to a spinal cord injury. However, axonal regeneration distal to injury is greatly diminished, accompanied by increased expression of astroglial and inflammatory markers at the injury site. Thus, the mammalian CNS undergoes an age-dependent decline in axon regeneration, as revealed when neuron-intrinsic growth state is elevated. These results have important implications for developing strategies to promote axonal repair after CNS injuries or diseases, which increasingly affect middle-aged to aging populations. PMID:27050519

  16. Transposable elements become active and mobile in the genomes of aging mammalian somatic tissues.

    PubMed

    De Cecco, Marco; Criscione, Steven W; Peterson, Abigail L; Neretti, Nicola; Sedivy, John M; Kreiling, Jill A

    2013-12-01

    Transposable elements (TEs) were discovered by Barbara McClintock in maize and have since been found to be ubiquitous in all living organisms. Transposition is mutagenic and organisms have evolved mechanisms to repress the activity of their endogenous TEs. Transposition in somatic cells is very low, but recent evidence suggests that it may be derepressed in some cases, such as cancer development. We have found that during normal aging several families of retrotransposable elements (RTEs) start being transcribed in mouse tissues. In advanced age the expression culminates in active transposition. These processes are counteracted by calorie restriction (CR), an intervention that slows down aging. Retrotransposition is also activated in age-associated, naturally occurring cancers in the mouse. We suggest that somatic retrotransposition is a hitherto unappreciated aging process. Mobilization of RTEs is likely to be an important contributor to the progressive dysfunction of aging cells. PMID:24323947

  17. Continuous administration of a P450 aromatase inhibitor induces polycystic ovary syndrome with a metabolic and endocrine phenotype in female rats at adult age.

    PubMed

    Maliqueo, Manuel; Sun, Miao; Johansson, Julia; Benrick, Anna; Labrie, Fernand; Svensson, Henrik; Lönn, Malin; Duleba, Antoni J; Stener-Victorin, Elisabet

    2013-01-01

    Studying the mechanisms for the complex pathogenesis of polycystic ovary syndrome (PCOS) requires animal models with endocrine, reproductive, and metabolic features of the syndrome. Hyperandrogenism seems to be a central factor in PCOS, leading to anovulation and insulin resistance. In female rats, continuous administration of letrozole, a nonsteroidal inhibitor of P450 aromatase, at 400 μg/d starting before puberty induces hyperandrogenemia and reproductive abnormalities similar to those in women with PCOS. However, despite high circulating testosterone levels, these rats do not develop metabolic abnormalities, perhaps because of their supraphysiological testosterone concentrations or because estrogen synthesis is completely blocked in insulin-sensitive tissues. To test the hypothesis that continuous administration of lower doses of letrozole starting before puberty would result in both metabolic and reproductive phenotypes of PCOS, we performed a 12-wk dose-response study. At 21 d of age, 46 female Wistar rats were divided into two letrozole groups (100 or 200 μg/d) and a control group (placebo). Both letrozole doses resulted in increased body weight, inguinal fat accumulation, anovulation, larger ovaries with follicular atresia and multiples cysts, endogenous hyperandrogemia, and lower estrogen levels. Moreover, rats that received 200 μg/d had insulin resistance and enlarged adipocytes in inguinal and mesenteric fat depots, increased circulating levels of LH, decreased levels of FSH, and increased ovarian expression of Cyp17a1 mRNA. Thus, continuous administration of letrozole, 200 μg/d, to female rats for 90 d starting before puberty results in a PCOS model with reproductive and metabolic features of the syndrome. PMID:23183180

  18. Mammalian Target of Rapamycin: Its Role in Early Neural Development and in Adult and Aged Brain Function.

    PubMed

    Garza-Lombó, Carla; Gonsebatt, María E

    2016-01-01

    The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging. PMID:27378854

  19. Mammalian Target of Rapamycin: Its Role in Early Neural Development and in Adult and Aged Brain Function

    PubMed Central

    Garza-Lombó, Carla; Gonsebatt, María E.

    2016-01-01

    The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging. PMID:27378854

  20. The Role of Mammalian Sirtuins in the Regulation of Metabolism, Aging, and Longevity

    PubMed Central

    Satoh, Akiko; Stein, Liana

    2013-01-01

    Ever since the discovery of sirtuins a decade ago, interest in this family of NAD-dependent deacetylases has exploded, generating multiple lines of evidence implicating sirtuins as evolutionarily conserved regulators of lifespan. In mammals, it has been established that sirtuins regulate physiological responses to metabolism and stress, two key factors that affect the process of aging. Further investigation into the intimate connection among sirtuins, metabolism, and aging has implicated the activation of SIRT1 as both preventative and therapeutic measures against multiple age-associated disorders including type 2 diabetes and Alzheimer’s disease. SIRT1 activation has clear potential to not only prevent age-associated diseases but also to extend healthspan and perhaps lifespan. Sirtuin activating compounds and NAD intermediates are two promising ways to achieve these elusive goals. PMID:21879449

  1. Structural characterization and anti-aging activity of a novel extracellular polysaccharide from fungus Phellinus sp. in a mammalian system.

    PubMed

    Ma, Xiao-Kui; Guo, Dan Dan; Peterson, Eric Charles; Dun, Ying; Li, Dan Yang

    2016-08-10

    Little is known about the chemical structure of purified extracellular polysaccharides from Phellinus sp., a fungal species with known medicinal properties. A combination of IR spectroscopy, methylation analysis and NMR were performed for the structural analysis of a purified extracellular polysaccharide derived from Phellinus sp. culture, denoted as SHP-1, along with an evaluation of the anti-aging effect in vivo of the polysaccharide supplementation. The structure of SHP-1 was established, with a backbone composed of →2,4)-α-d-glucopyranose-(1→ and →2)-β-d-mannopyranose-(1→ and two terminal glucopyranose branches. Biochemical analysis from mammalian animal experiments demonstrated that SHP-1 possesses the ability to enhance antioxidant enzyme activities, such as catalase (CAT) and superoxide dismutase (SOD) activities, Trolox equivalent antioxidant capacity (TEAC) in serum of d-galactose-aged mice, while reducing lipofuscin levels, another indicator of cell aging, indicating a potential association with anti-aging activities in a dose dependent manner. This compound had a favourable influence on immune organ indices, and a marked amelioration ability of histopathological hepatic lesions such as necrosis, karyolysis and reduced inflammation and apoptosis in mouse hepatocytes. These results suggest that SHP-1 has strong antioxidant activities and a significant protective effect against oxidative stress or hepatotoxicity induced by d-galactose in mice and it could be developed as a food ingredient or a pharmaceutical to prevent many age-associated diseases such as major depressive disorder and hepatotoxicity. To our knowledge, this is the first report on the antioxidant effects of a novel purified exopolysaccharide derived from Phellinus sp. PMID:27405813

  2. Polycystic Ovary Syndrome FAQ

    MedlinePlus

    f AQ FREQUENTLY ASKED QUESTIONS FAQ121 GYNECOLOGIC PROBLEMS Polycystic Ovary Syndrome (PCOS) • What are common signs and symptoms of polycystic ovary syndrome (PCOS)? • What causes PCOS? • What is insulin resistance? • ...

  3. Polycystic Ovary Syndrome

    MedlinePlus

    Polycystic ovary syndrome (PCOS) happens when a woman's ovaries or adrenal glands produce more male hormones than normal. One result is that cysts ( ... who are obese are more likely to have polycystic ovary syndrome. Symptoms of PCOS include: Infertility Pelvic pain Excess ...

  4. Spatial and Age-Dependent Hair Cell Generation in the Postnatal Mammalian Utricle.

    PubMed

    Gao, Zhen; Kelly, Michael C; Yu, Dehong; Wu, Hao; Lin, Xi; Chi, Fang-Lu; Chen, Ping

    2016-04-01

    Loss of vestibular hair cells is a common cause of balance disorders. Current treatment options for bilateral vestibular dysfunction are limited. During development, atonal homolog 1 (Atoh1) is sufficient and necessary for the formation of hair cells and provides a promising gene target to induce hair cell generation in the mammals. In this study, we used a transgenic mouse line to test the age and cell type specificity of hair cell induction in the postnatal utricle in mice. We found that forced Atoh1 expression in vivo can induce hair cell formation in the utricle from postnatal days 1 to 21, while the efficacy of hair cell induction is progressively reduced as the animals become older. In the utricle, the induction of hair cells occurs both within the sensory region and in cells in the transitional epithelium next to the sensory region. Within the sensory epithelium, the central region, known as the striola, is most subjective to the induction of hair cell formation. Furthermore, forced Atoh1 expression can promote proliferation in an age-dependent manner that mirrors the progressively reduced efficacy of hair cell induction in the postnatal utricle. These results suggest that targeting both cell proliferation and Atoh1 in the utricle striolar region may be explored to induce hair cell regeneration in mammals. The study also demonstrates the usefulness of the animal model that provides an in vivo Atoh1 induction model for vestibular regeneration studies. PMID:25666161

  5. Polycystic ovary syndrome.

    PubMed

    Azziz, Ricardo; Carmina, Enrico; Chen, ZiJiang; Dunaif, Andrea; Laven, Joop S E; Legro, Richard S; Lizneva, Daria; Natterson-Horowtiz, Barbara; Teede, Helena J; Yildiz, Bulent O

    2016-01-01

    Polycystic ovary syndrome (PCOS) affects 5-20% of women of reproductive age worldwide. The condition is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology (PCOM) - with excessive androgen production by the ovaries being a key feature of PCOS. Metabolic dysfunction characterized by insulin resistance and compensatory hyperinsulinaemia is evident in the vast majority of affected individuals. PCOS increases the risk for type 2 diabetes mellitus, gestational diabetes and other pregnancy-related complications, venous thromboembolism, cerebrovascular and cardiovascular events and endometrial cancer. PCOS is a diagnosis of exclusion, based primarily on the presence of hyperandrogenism, ovulatory dysfunction and PCOM. Treatment should be tailored to the complaints and needs of the patient and involves targeting metabolic abnormalities through lifestyle changes, medication and potentially surgery for the prevention and management of excess weight, androgen suppression and/or blockade, endometrial protection, reproductive therapy and the detection and treatment of psychological features. This Primer summarizes the current state of knowledge regarding the epidemiology, mechanisms and pathophysiology, diagnosis, screening and prevention, management and future investigational directions of the disorder. PMID:27510637

  6. Carcinoma of the Ovary

    PubMed Central

    Weekes, Leroy R.; Watkins, Sue A.

    1981-01-01

    The data for this paper are based on 50 patients discharged from the Queen of Angels Hospital with a diagnosis of carcinoma of the ovary from 1972 to 1978. Currently, ovarian cancer is the leading cause of death of all pelvic malignancies. Peak incidence of ovarian cancer is found in women between 40 to 65 years of age. Symptomatology includes often vague abdominal discomfort, dyspepsia, and other digestive disorders which may be present for several months prior to diagnosis. The workup for suspected ovarian cancer should include a careful history, physical examination, pelvic, and rectal examinations, Pap smear, CBC, urinalysis, SMA 12 (blood chemistries), chest x-ray, and intravenous pyelography as indicated. Sonography, lymphangiography are optional. Traditionally, operative treatment has been the keystone of management for ovarian carcinoma. In view of the unsatisfactory results with operation and radiotherapy in disseminated disease, chemotherapy has been used widely. Hope for the future lies in further development of immunodiagnosis and immunotherapy. PMID:7310921

  7. Gene expression in subcutaneous adipose tissue differs in women with polycystic ovary syndrome and controls matched pair-wise for age, body weight, and body mass index

    PubMed Central

    Mannerås-Holm, Louise; Benrick, Anna; Stener-Victorin, Elisabet

    2014-01-01

    Adipose tissue dysfunction may be a central factor in the pathogenesis of insulin resistance in women with polycystic ovary syndrome (PCOS). Gene expression in subcutaneous adipose tissue in PCOS and its relation to metabolic and endocrine features of the syndrome have been fragmentarily investigated. The aim was to assess in subcutaneous adipose tissue the expression of genes potentially associated with adipose tissue dysfunction and to explore their relation to features of the syndrome. Twenty-one women with PCOS (body mass index [BMI] 18.2–33.4 kg/m2) and 21 controls (BMI 19.2–31.7 kg/m2) were matched pair-wise for age, body weight, and BMI. Tissue biopsies were obtained to measure mRNA expression of 44 genes (TaqMan Low Density Array). Differential expression levels were correlated with BMI, glucose infusion rate (GIR), sex hormone binding globulin (SHBG), and sex steroids. In PCOS, expression of adiponectin receptor 2 (ADIPOR2), LPL, and twist-related protein 1 (TWIST1) was decreased, while expression of chemokine (C-C motif) ligand 2 (CCL2) and heme oxygenase (decycling 1) (HMOX1) was increased. TWIST1 and HMOX1, both novel adipokines, correlated with BMI and GIR. After BMI adjustment, LPL and ADIPOR2 expression correlated with plasma estradiol, and CCL2 expression correlated with GIR, in all women. We conclude that adipose tissue mRNA expression differed in PCOS women and controls and that two novel adipokines, TWIST1 and HMOX1, together with adiponectin, LPL, and CCL2, and their downstream pathways merit further investigation. PMID:25068085

  8. From heterochromatin islands to the NAD World: a hierarchical view of aging through the functions of mammalian Sirt1 and systemic NAD biosynthesis.

    PubMed

    Imai, Shin-ichiro

    2009-10-01

    For the past couple of decades, aging science has been rapidly evolving, and powerful genetic tools have identified a variety of evolutionarily conserved regulators and signaling pathways for the control of aging and longevity in model organisms. Nonetheless, a big challenge still remains to construct a comprehensive concept that could integrate many distinct layers of biological events into a systemic, hierarchical view of aging. The "heterochromatin island" hypothesis was originally proposed 10 years ago to explain deterministic and stochastic aspects of cellular and organismal aging, which drove the author to the study of evolutionarily conserved Sir2 proteins. Since a surprising discovery of their NAD-dependent deacetylase activity, Sir2 proteins, now called "sirtuins," have been emerging as a critical epigenetic regulator for aging. In this review, I will follow the process of conceptual development from the heterochromatin island hypothesis to a novel, comprehensive concept of a systemic regulatory network for mammalian aging, named "NAD World," summarizing recent studies on the mammalian NAD-dependent deacetylase Sirt1 and nicotinamide phosphoribosyltransferase (Nampt)-mediated systemic NAD biosynthesis. This new concept of the NAD World provides critical insights into a systemic regulatory mechanism that fundamentally connects metabolism and aging and also conveys the ideas of functional hierarchy and frailty for the regulation of aging in mammals. PMID:19289152

  9. [Diagnostics of polycystic ovary syndrome].

    PubMed

    Lazúrová, Ivica; Figurová, Jana; Lazúrová, Zora

    2015-12-01

    Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy among women of reproductive age and the most frequent cause of menstruation cycle disorders. It is marked by a hyperandrogenic state (clinical and/or biochemical) and ovulatory dysfunction (anovulation and/or ultrasonographic finding of polycystic ovaries), which are also criteria for its diagnosis according to Androgen Excess and PCOS Society. The syndrome has multiple phenotypic expressions, among them besides the above characteristics also a metabolic syndrome, primarily obesity and insulin resistance. Diagnosing of PCOS may be rather exacting in clinical practice and it remains to be a diagnosis per exclusionem, following elimination of other causes of hyperandrogenic state and chronic oligo-anovulation. It requires a close cooperation between a gynecologist and endocrinologist and with regard to frequent metabolic complications also with an internist, diabetologist and possibly cardiologist. PMID:27124971

  10. Metabolic Syndrome: Polycystic Ovary Syndrome.

    PubMed

    Mortada, Rami; Williams, Tracy

    2015-08-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous condition characterized by androgen excess, ovulatory dysfunction, and polycystic ovaries. It is the most common endocrinopathy among women of reproductive age, affecting between 6.5% and 8% of women, and is the most common cause of infertility. Insulin resistance is almost always present in women with PCOS, regardless of weight, and they often develop diabetes and metabolic syndrome. The Rotterdam criteria are widely used for diagnosis. These criteria require that patients have at least two of the following conditions: hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The diagnosis of PCOS also requires exclusion of other potential etiologies of hyperandrogenism and ovulatory dysfunction. The approach to PCOS management differs according to the presenting symptoms and treatment goals, particularly the patient's desire for pregnancy. Weight loss through dietary modifications and exercise is recommended for patients with PCOS who are overweight. Oral contraceptives are the first-line treatment for regulating menstrual cycles and reducing manifestations of hyperandrogenism, such as acne and hirsutism. Clomiphene is the first-line drug for management of anovulatory infertility. Metformin is recommended for metabolic abnormalities such as prediabetes, and a statin should be prescribed for cardioprotection if the patient meets standard criteria for statin therapy. PMID:26280343

  11. A comprehensive transcriptomic analysis of infant and adult mouse ovary.

    PubMed

    Pan, Linlin; Gong, Wei; Zhou, Yuanyuan; Li, Xiaonuan; Yu, Jun; Hu, Songnian

    2014-10-01

    Ovary development is a complex process involving numerous genes. A well-developed ovary is essential for females to keep fertility and reproduce offspring. In order to gain a better insight into the molecular mechanisms related to the process of mammalian ovary development, we performed a comparative transcriptomic analysis on ovaries isolated from infant and adult mice by using next-generation sequencing technology (SOLiD). We identified 15,454 and 16,646 transcriptionally active genes at the infant and adult stage, respectively. Among these genes, we also identified 7021 differentially expressed genes. Our analysis suggests that, in general, the adult ovary has a higher level of transcriptomic activity. However, it appears that genes related to primordial follicle development, such as those encoding Figla and Nobox, are more active in the infant ovary, whereas expression of genes vital for follicle development, such as Gdf9, Bmp4 and Bmp15, is upregulated in the adult. These data suggest a dynamic shift in gene expression during ovary development and it is apparent that these changes function to facilitate follicle maturation, when additional functional gene studies are considered. Furthermore, our investigation has also revealed several important functional pathways, such as apoptosis, MAPK and steroid biosynthesis, that appear to be much more active in the adult ovary compared to those of the infant. These findings will provide a solid foundation for future studies on ovary development in mice and other mammals and help to expand our understanding of the complex molecular and cellular events that occur during postnatal ovary development. PMID:25251848

  12. Polycystic ovary disease

    MedlinePlus

    ... hormones. This may lead to changes in the menstrual cycle, cysts in the ovaries , trouble getting pregnant, and ... Symptoms Symptoms of PCOS include changes in the menstrual cycle, such as: Not getting a period after you ...

  13. Polycystic Ovary Syndrome in Adolescents.

    PubMed

    Witchel, Selma Feldman; Roumimper, Hailey; Oberfield, Sharon

    2016-06-01

    Polycystic ovary syndrome (PCOS) is a familial heterogeneous disorder affecting 6% to 10% of reproductive-age women. The use of criteria developed for adult women is problematic for the adolescent girl because the clinical features associated with PCOS are normal pubertal events. The recent consensus statement on PCOS in adolescents stated that hyperandrogenism and oligomenorrhea need to persist for at least 2 years to consider the diagnosis of PCOS. Although insulin resistance, hyperinsulinism, and obesity are often associated with PCOS, these features are not considered valid diagnostic criteria. Recent genomewide association studies implicate genetic loci involved in the hypothalamic-pituitary-ovarian axis. PMID:27241968

  14. Abnormal gene expression profiles in human ovaries from polycystic ovary syndrome patients.

    PubMed

    Jansen, Erik; Laven, Joop S E; Dommerholt, Henri B R; Polman, Jan; van Rijt, Cindy; van den Hurk, Caroline; Westland, Jolanda; Mosselman, Sietse; Fauser, Bart C J M

    2004-12-01

    Polycystic ovary syndrome (PCOS) represents the most common cause of anovulatory infertility and affects 5-10% of women of reproductive age. The etiology of PCOS is still unknown. The current study is the first to describe consistent differences in gene expression profiles in human ovaries comparing PCOS patients vs. healthy normoovulatory individuals. The microarray analysis of PCOS vs. normal ovaries identifies dysregulated expression of genes encoding components of several biological pathways or systems such as Wnt signaling, extracellular matrix components, and immunological factors. Resulting data may provide novel clues for ovarian dysfunction in PCOS. Intriguingly, the gene expression profiles of ovaries from (long-term) androgen-treated female-to-male transsexuals (TSX) show considerable overlap with PCOS. This observation provides supportive evidence that androgens play a key role in the pathogenesis of PCOS. Presented data may contribute to a better understanding of dysregulated pathways in PCOS, which might ultimately reveal novel leads for therapeutic intervention. PMID:15308691

  15. A bovine model for polycystic ovary syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polycystic ovary syndrome (PCOS) results in the greatest single cause of anovulatory infertility in reproductive age women (affecting 5-10%). Previously, research groups have created animal models utilizing non-human primates and sheep to better understand the mechanisms involved in PCOS. However, c...

  16. Diagnosis and Treatment of Polycystic Ovary Syndrome.

    PubMed

    Williams, Tracy; Mortada, Rami; Porter, Samuel

    2016-07-15

    Polycystic ovary syndrome is the most common endocrinopathy among reproductive-aged women in the United States, affecting approximately 7% of female patients. Although the pathophysiology of the syndrome is complex and there is no single defect from which it is known to result, it is hypothesized that insulin resistance is a key factor. Metabolic syndrome is twice as common in patients with polycystic ovary syndrome compared with the general population, and patients with polycystic ovary syndrome are four times more likely than the general population to develop type 2 diabetes mellitus. Patient presentation is variable, ranging from asymptomatic to having multiple gynecologic, dermatologic, or metabolic manifestations. Guidelines from the Endocrine Society recommend using the Rotterdam criteria for diagnosis, which mandate the presence of two of the following three findings- hyperandrogenism, ovulatory dysfunction, and polycystic ovaries-plus the exclusion of other diagnoses that could result in hyperandrogenism or ovulatory dysfunction. It is reasonable to delay evaluation for polycystic ovary syndrome in adolescent patients until two years after menarche. For this age group, it is also recommended that all three Rotterdam criteria be met before the diagnosis is made. Patients who have marked virilization or rapid onset of symptoms require immediate evaluation for a potential androgen-secreting tumor. Treatment of polycystic ovary syndrome is individualized based on the patient's presentation and desire for pregnancy. For patients who are overweight, weight loss is recommended. Clomiphene and letrozole are first-line medications for infertility. Metformin is the first-line medication for metabolic manifestations, such as hyperglycemia. Hormonal contraceptives are first-line therapy for irregular menses and dermatologic manifestations. PMID:27419327

  17. Effects of trifluralin on the mouse ovary.

    PubMed

    Cecconi, Sandra; Rossi, Gianna; Carta, Gaspare; Di Luigi, Gianluca; Cellini, Valerio; Canipari, Rita; Buccione, Roberto

    2013-04-01

    Trifluralin, a herbicide used to protect many arable and horticultural crops, was evaluated for its potential toxicity on the mammalian ovary. To this end, adult female mice were fed or not (control) with a trifluralin-enriched diet (150 mg/kg body weight/day) during gestation and lactation. After weaning, 3-week-old female mice from either trifluralin-treated or control groups were used to evaluate whether the exposure to this herbicide in utero and during lactation could induce stress responses in the ovary. It was found that trifluralin exposure caused a significantly higher level of p53, but not of pRb, in the whole ovary, and in particular in granulosa cells. TUNEL staining showed that herbicide treatment did not increase the apoptotic index of the somatic compartment. Also oocyte fertilizability was unaffected, as metaphase II oocytes retrieved from treated mice were capable of forming male and female pronuclei after in vitro fertilization as control mice. However, trifluralin determined a slightly higher number of oocytes with cytoplasmic degeneration compared with control animals. In conclusion, our results suggest that exposure to a low trifluralin dose during pregnancy and lactation does not impair oocyte quality, but can induce a stress response in ovarian somatic cells. PMID:21544921

  18. Reproductive patterns result from age-related sensitivity to resources and reproductive costs in a mammalian carnivore.

    PubMed

    Rauset, Geir Rune; Low, Matthew; Persson, Jens

    2015-12-01

    Although the effects of individual age, resource availability, and reproductive costs have been extensively studied to understand the causes of variation in reproductive output, there are almost no studies showing how these factors interact in explaining this variation. To examine this interaction, we used longitudinal demographic data from an 18-year study of 53 breeding female wolverines (Gulo gulo), and corresponding environmental data from their individual home ranges. Females showed a typical age-related pattern in reproductive output, with an initial increase followed by a senescent decline in later years. This pattern was largely driven by four processes: (1) physiological/behavioral maturation between ages two and three; (2) age-related differences in the costs of reproduction resulting in an initial increase, and then a declining probability of breeding two years in a row as individuals aged; (3) resource availability (reindeer [Rangifer tarandus] carcass abundance; mostly Eurasian lynx [Lynx lynx] kills) in the months preceding parturition, which influenced the probability of having cubs, but only for individuals that had successfully bred in the previous year; and (4) resource availability also influenced the cost of reproduction in an age-dependent manner, as prime age females that had bred in the previous year were more responsive to resource availability than those at other ages. This study demonstrates that by examining how drivers of reproductive variation interact, we can get a much clearer understanding of the mechanisms responsible for age-related patterns of reproduction. This has implications not only for general ecological theory, but will also allow better predictions of population resnonses to environmental changes or management based on a population's age-structure. PMID:26909422

  19. Morphological features of the ovaries during Oogenesis of the Oriental fruit fly (Bactrocera dorsalis Hendel) in relation to the physiological age

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Determination of physiological state (age?) in insects is useful in furthering our understanding of how insect behavior changes with age. Central to this determination is the identification of characters that allow assessment of physiological age. While non-destructive measures are the most desired ...

  20. Diverse Roles of Growth Hormone and Insulin-Like Growth Factor-1 in Mammalian Aging: Progress and Controversies

    PubMed Central

    Csiszar, Anna; de Cabo, Raphael; Ferrucci, Luigi; Ungvari, Zoltan

    2012-01-01

    Because the initial reports demonstrating that circulating growth hormone and insulin-like growth factor-1 decrease with age in laboratory animals and humans, there have been numerous studies related to the importance of these hormones for healthy aging. Nevertheless, the role of these potent anabolic hormones in the genesis of the aging phenotype remains controversial. In this chapter, we review the studies demonstrating the beneficial and deleterious effects of growth hormone and insulin-like growth factor-1 deficiency and explore their effects on specific tissues and pathology as well as their potentially unique effects early during development. Based on this review, we conclude that the perceived contradictory roles of growth hormone and insulin-like growth factor-1 in the genesis of the aging phenotype should not be interpreted as a controversy on whether growth hormone or insulin-like growth factor-1 increases or decreases life span but rather as an opportunity to explore the complex roles of these hormones during specific stages of the life span. PMID:22522510

  1. Stem Cells, Progenitor Cells, and Lineage Decisions in the Ovary

    PubMed Central

    Hummitzsch, Katja; Anderson, Richard A.; Wilhelm, Dagmar; Wu, Ji; Telfer, Evelyn E.; Russell, Darryl L.; Robertson, Sarah A.

    2015-01-01

    Exploring stem cells in the mammalian ovary has unleashed a Pandora's box of new insights and questions. Recent evidence supports the existence of stem cells of a number of the different cell types within the ovary. The evidence for a stem cell model producing mural granulosa cells and cumulus cells is strong, despite a limited number of reports. The recent identification of a precursor granulosa cell, the gonadal ridge epithelial-like cell, is exciting and novel. The identification of female germline (oogonial) stem cells is still very new and is currently limited to just a few species. Their origins and physiological roles, if any, are unknown, and their potential to produce oocytes and contribute to follicle formation in vivo lacks robust evidence. The precursor of thecal cells remains elusive, and more compelling data are needed. Similarly, claims of very small embryonic-like cells are also preliminary. Surface epithelial cells originating from gonadal ridge epithelial-like cells and from the mesonephric epithelium at the hilum of the ovary have also been proposed. Another important issue is the role of the stroma in guiding the formation of the ovary, ovigerous cords, follicles, and surface epithelium. Immune cells may also play key roles in developmental patterning, given their critical roles in corpora lutea formation and regression. Thus, while the cellular biology of the ovary is extremely important for its major endocrine and fertility roles, there is much still to be discovered. This review draws together the current evidence and perspectives on this topic. PMID:25541635

  2. Mammalian pheromones.

    PubMed

    Liberles, Stephen D

    2014-01-01

    Mammalian pheromones control a myriad of innate social behaviors and acutely regulate hormone levels. Responses to pheromones are highly robust, reproducible, and stereotyped and likely involve developmentally predetermined neural circuits. Here, I review several facets of pheromone transduction in mammals, including (a) chemosensory receptors and signaling components of the main olfactory epithelium and vomeronasal organ involved in pheromone detection; (b) pheromone-activated neural circuits subject to sex-specific and state-dependent modulation; and (c) the striking chemical diversity of mammalian pheromones, which range from small, volatile molecules and sulfated steroids to large families of proteins. Finally, I review (d) molecular mechanisms underlying various behavioral and endocrine responses, including modulation of puberty and estrous; control of reproduction, aggression, suckling, and parental behaviors; individual recognition; and distinguishing of own species from predators, competitors, and prey. Deconstruction of pheromone transduction mechanisms provides a critical foundation for understanding how odor response pathways generate instinctive behaviors. PMID:23988175

  3. Mammalian Pheromones

    PubMed Central

    Liberles, Stephen D.

    2015-01-01

    Mammalian pheromones control a myriad of innate social behaviors and acutely regulate hormone levels. Responses to pheromones are highly robust, reproducible, and stereotyped and likely involve developmentally predetermined neural circuits. Here, I review several facets of pheromone transduction in mammals, including (a) chemosensory receptors and signaling components of the main olfactory epithelium and vomeronasal organ involved in pheromone detection; (b) pheromone-activated neural circuits subject to sex-specific and state-dependent modulation; and (c) the striking chemical diversity of mammalian pheromones, which range from small, volatile molecules and sulfated steroids to large families of proteins. Finally, I review (d ) molecular mechanisms underlying various behavioral and endocrine responses, including modulation of puberty and estrous; control of reproduction, aggression, suckling, and parental behaviors; individual recognition; and distinguishing of own species from predators, competitors, and prey. Deconstruction of pheromone transduction mechanisms provides a critical foundation for understanding how odor response pathways generate instinctive behaviors. PMID:23988175

  4. Complementary Therapy in Polycystic Ovary Syndrome

    PubMed Central

    Aquino, C. I.; Nori, S. L.

    2014-01-01

    Polycystic Ovary Syndrome (PCOS) is an endocrine disease. PCOS afflicts 5 to 10 % of women of reproductive age. The symptoms are: amenorrhea, oligomenorrhea, hirsutism, obesity, infertility, chronic hyperandrogenic anovulation and acne. Other risk factors aggravate this condition: insulin resistance, obesity, hypertension, dyslipidemia, inflammation and subclinical cardiovascular disease. Anxiety, depression and reduced quality of life are also common. This review highlights the mechanisms and the beneficial effects of acupuncture, exercise and resveratrol on animal models and on humans affected by PCOS. PMID:24809037

  5. Sirtuins: Guardians of Mammalian Healthspan

    PubMed Central

    Giblin, William; Skinner, Mary E.; Lombard, David B.

    2014-01-01

    The first link between sirtuins and longevity was made 15 years ago in yeast. These initial studies sparked efforts by many laboratories working in diverse model organisms to elucidate the relationships between sirtuins, lifespan, and age-associated dysfunction. Here we discuss the current understanding of how sirtuins relate to aging. We focus primarily on mammalian sirtuins SIRT1, SIRT3, and SIRT6, the three sirtuins for which the most relevant data are available. Strikingly, a large body of evidence now indicates that these and other mammalian sirtuins suppress a variety of age-related pathologies and promote healthspan. Moreover, increased expression of SIRT1 or SIRT6 extends mouse lifespan. Overall, these data point to important roles for sirtuins in promoting mammalian health, and perhaps in modulating the aging process. PMID:24877878

  6. Mammalian development in space

    NASA Technical Reports Server (NTRS)

    Ronca, April E.

    2003-01-01

    Life on Earth, and thus the reproductive and ontogenetic processes of all extant species and their ancestors, evolved under the constant influence of the Earth's l g gravitational field. These considerations raise important questions about the ability of mammals to reproduce and develop in space. In this chapter, I review the current state of our knowledge of spaceflight effects on developing mammals. Recent studies are revealing the first insights into how the space environment affects critical phases of mammalian reproduction and development, viz., those events surrounding fertilization, embryogenesis, pregnancy, birth, postnatal maturation and parental care. This review emphasizes fetal and early postnatal life, the developmental epochs for which the greatest amounts of mammalian spaceflight data have been amassed. The maternal-offspring system, the coordinated aggregate of mother and young comprising mammalian development, is of primary importance during these early, formative developmental phases. The existing research supports the view that biologically meaningful interactions between mothers and offspring are changed in the weightlessness of space. These changes may, in turn, cloud interpretations of spaceflight effects on developing offspring. Whereas studies of mid-pregnant rats in space have been extraordinarily successful, studies of young rat litters launched at 9 days of postnatal age or earlier, have been encumbered with problems related to the design of in-flight caging and compromised maternal-offspring interactions. Possibilities for mammalian birth in space, an event that has not yet transpired, are considered. In the aggregate, the results indicate a strong need for new studies of mammalian reproduction and development in space. Habitat development and systematic ground-based testing are important prerequisites to future research with young postnatal rodents in space. Together, the findings support the view that the environment within which young

  7. Anti-Müllerian hormone inhibits initiation of primordial follicle growth in the mouse ovary.

    PubMed

    Durlinger, Alexandra L L; Gruijters, Maria J G; Kramer, Piet; Karels, Bas; Ingraham, Holly A; Nachtigal, Mark W; Uilenbroek, Jan Th J; Grootegoed, J Anton; Themmen, Axel P N

    2002-03-01

    Recruitment of primordial follicles is essential for female fertility; however, the exact mechanisms regulating this process are largely unknown. Earlier studies using anti-Müllerian hormone (AMH)-deficient mice suggested that AMH is involved in the regulation of primordial follicle recruitment. We tested this hypothesis in a neonatal ovary culture system, in which ovaries from 2-d-old C57Bl/6J mice were cultured for 2 or 4 d in the absence or presence of AMH. Ovaries from 2-d-old mice contain multiple primordial follicles, some naked oocytes, and no follicles at later stages of development. We observed that in the cultured ovaries, either nontreated or AMH-treated, follicular development progressed to the same extent as in in vivo ovaries of comparable age, confirming the validity of our culture system. However, in the presence of AMH, cultured ovaries contained 40% fewer growing follicles compared with control ovaries. A similar reduction was found after 4 d of culture. Consistent with these findings, we noted lower inhibin alpha-subunit expression in AMH-treated ovaries compared with untreated ovaries. In contrast, expression of AMH ligand type II receptor and the expression of oocyte markers growth and differentiation factor 9 and zona pellucida protein 3 were not influenced by AMH. Based on the results, we suggest that AMH inhibits initiation of primordial follicle growth and therefore functions as an inhibitory growth factor in the ovary during these early stages of folliculogenesis. PMID:11861535

  8. Mammalian target of rapamycin/p70 ribosomal S6 protein kinase signaling is altered by sevoflurane and/or surgery in aged rats.

    PubMed

    Liu, Yongzhe; Ma, Li; Jiao, Linbo; Gao, Minglong; Guo, Wenzhi; Chen, Lin; Pan, Ningling; Ma, Yaqun

    2015-12-01

    The mammalian target of rapamycin (mTOR)/p70 ribosomal S6 protein kinase (p70S6k) pathway exerts anti‑apoptotic effects that may contribute to disease pathogenesis. The memory impairment in patients with Alzheimer's disease (AD) has been suggested to be contributed to by abnormal mTOR signaling. The aim of the current study was to investigate the association between sevoflurane and/or surgery and AD through the mTOR/p70S6K signaling pathway. Sprague‑Dawley rats were randomly assigned to the sevoflurane, surgery or control groups. The animals in the surgery group received a partial hepatectomy under sevoflurane anesthesia. The hippocampal levels of phosphorylated (p)‑mTOR, p‑p70S6K, caspase‑3 and p‑tau/total (t)‑tau were analyzed. The Morris water maze (MWM) was used to evaluate cognitive function following treatment. The levels of p‑mTOR and p‑p70S6K were reduced, whereas caspase‑3 levels were increased in the surgery group compared with the sevoflurane group. The p‑tau/t‑tau levels were increased, however, tau mRNA was unaffected by sevoflurane and/or surgery. The rats in the surgery group required a significantly longer time to locate the platform in the MWM test compared with the control and sevoflurane groups. Sevoflurane treatment and/or surgery reduced anti‑apoptotic activity, and the postoperative cognitive dysfunction following surgery may be due to mTOR signaling pathway inhibition in aged rats. Increased neuronal apoptosis and tau phosphorylation are suggested to be involved in the association between anesthesia and AD occurrence. PMID:26497858

  9. Mammalian sleep

    NASA Astrophysics Data System (ADS)

    Staunton, Hugh

    2005-05-01

    This review examines the biological background to the development of ideas on rapid eye movement sleep (REM sleep), so-called paradoxical sleep (PS), and its relation to dreaming. Aspects of the phenomenon which are discussed include physiological changes and their anatomical location, the effects of total and selective sleep deprivation in the human and animal, and REM sleep behavior disorder, the latter with its clinical manifestations in the human. Although dreaming also occurs in other sleep phases (non-REM or NREM sleep), in the human, there is a contingent relation between REM sleep and dreaming. Thus, REM is taken as a marker for dreaming and as REM is distributed ubiquitously throughout the mammalian class, it is suggested that other mammals also dream. It is suggested that the overall function of REM sleep/dreaming is more important than the content of the individual dream; its function is to place the dreamer protagonist/observer on the topographical world. This has importance for the developing infant who needs to develop a sense of self and separateness from the world which it requires to navigate and from which it is separated for long periods in sleep. Dreaming may also serve to maintain a sense of ‘I’ness or “self” in the adult, in whom a fragility of this faculty is revealed in neurological disorders.

  10. Mammalian aromatases.

    PubMed

    Conley, A; Hinshelwood, M

    2001-05-01

    Aromatase is the enzyme complex that catalyses the synthesis of oestrogens from androgens, and therefore it has unique potential to influence the physiological balance between the sex steroid hormones. Both aromatase cytochrome P450 (P450arom) and NADPH-cytochrome P450 reductase (reductase), the two essential components of the enzyme complex, are highly conserved among mammals and vertebrates. Aromatase expression occurs in the gonads and brain, and is essential for reproductive development and fertility. Of interest are the complex mechanisms involving alternative promoter utilization that have evolved to control tissue-specific expression in these tissues. In addition, in a number of species, including humans, expression of aromatase has a broader tissue distribution, including placenta, adipose and bone. The relevance of oestrogen synthesis and possibly androgen metabolism in these peripheral sites of expression is now becoming clear from studies in P450arom knockout (ArKO) mice and from genetic defects recognized recently in both men and women. Important species differences in the physiological roles of aromatase expression are also likely to emerge, despite the highly conserved nature of the enzyme system. The identification of functionally distinct, tissue-specific isozymes of P450arom in at least one mammal, pigs, and several species of fish indicates that there are additional subtle, but physiologically significant, species-specific roles for aromatase. Comparative studies of mammalian and other vertebrate aromatases will expand understanding of the role played by this ancient enzyme system in the evolution of reproduction and the adaptive influence of oestrogen synthesis on general health and well being. PMID:11427156

  11. Oral contraceptives in polycystic ovary syndrome.

    PubMed

    Helvaci, N; Yildiz, B O

    2014-09-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of women of reproductive age and combined oral contraceptives (OCs) are often the first-line treatment of the syndrome by improving hyperandrogenism and regulating menstrual cycles. Oral contraceptives have some cardiovascular and metabolic effects that varies among different formulations depending upon the dose and type of the both estrogen and progestin components. These cardiometabolic effects of OCs raise some concerns about their long-term use in PCOS, but available data suggest that the benefits outweigh the risks. More studies are needed to clarify the safety of long-term use of OCs in PCOS. PMID:25003228

  12. Tumours of the ovary

    PubMed Central

    Nielsen, Svend W.; Misdorp, W.; McEntee, Kenneth

    1976-01-01

    Ovarian tumours are common in animals, the majority occurring in bitches and cows. The two most important germ cell tumours were dysgerminoma and teratoma; these morphologically resemble their counterparts in women, with the exception that teratomas in animals tend less to malignancy. The granulosa cell tumour is the most frequent sex cord-stromal tumour in all six species and it may contain luteinized areas or show differentiation towards a Sertoli cell pattern. The canine papillary adenoma and papillary adenocarcinoma, which are as common as granulosa tumours, have several features in common with their counterparts in women: they are of similar histological appearance, are frequently bilateral, and the adenocarcinomas have a great propensity for peritoneal implantation metastasis. Ovarian cysts are frequent in the bitch, sow, and cow and may originate from five different anatomical structures in the ovary. ImagesFig. 1Fig. 2 and 3Fig. 20-22Fig. 8-10Fig. 15 and 16Fig. 23Fig. 24Fig. 25Fig. 26Fig. 17-19Fig. 4 and 5Fig. 6 and 7Fig. 11Fig. 12Fig. 13 and 14 PMID:1086151

  13. [Polycystic ovary syndrome].

    PubMed

    Vrbíková, Jana

    2015-10-01

    For diagnosing of polycystic ovary syndrome (PCOS) it is currently recommended to follow the ESHRE criteria. For diagnosis according to them two of the following three symptoms are sufficient: 1. morphology of polycystic ovaria, 2. clinical manifestations of hyperandrogenism or laboratory proof of hyperandrogenemia, and 3. oligo-anovulation. PCOS is a complex disorder in whose pathogenesis genetic and environmental effects interact. It is not a gynecological disorder alone, the syndrome is accompanied by insulin resistance which leads to increased incidence of type 2 diabetes mellitus and impaired glucose tolerance (4 times and twice, independently of BMI). Also gestational DM occurs more frequently. Dyslipidemia, arterial hypertension, elevated CRP and homocysteine levels, endothelial dysfunction and greater intima-media thickness are also more frequent. It is not quite clear, however, whether women with PCOS suffer cardiovascular events more frequently as well. More often than is accidental PCOS is associated with depression, anxiety and eating disorders, further with nonalcoholic steatohepatitis and with the sleep apnoea syndrome - especially in obese women. Therapeutic measures include non-pharmacological methods - lifestyle adjustments focused on weight reduction in obese individuals, cosmetic measures for dermatologic manifestation of hyperandrogenism, in particular laser and pharmacotherapy (combined hormonal contraceptives and antiandrogens). Menstrual irregularities can be treated with contraceptives or cyclical administration of gestagens, also metformin can be used. PMID:26486483

  14. Characterization of ornithine decarboxylase of tobacco cells and tomato ovaries.

    PubMed Central

    Heimer, Y M; Mizrahi, Y

    1982-01-01

    Some characteristics of L-ornithine decarboxylase of tomato ovaries and tobacco cells are described. The enzyme has a pH optimum of 8.0. It requires pyridoxal phosphate and thiol reagent (dithiothreitol) for activity. It is specific for L-ornithine and has an apparent Km of 1.4 X 10-4 M. It has an apparent molecular weight of 107000. Putrescine inhibited the activity in vitro. Spermidine and spermine also inhibit the enzyme, but less effectively. It is concluded that the enzyme is similar to that of mammalian origin and likewise fulfils a function related to cell proliferation. PMID:7082296

  15. Cryopreservation of ovaries from neonatal marmoset monkeys

    PubMed Central

    Motohashi, Hideyuki H.; Ishibashi, Hidetoshi

    2016-01-01

    The ovary of neonatal nonhuman primates contains the highest number of immature oocytes, but its cryopreservation has not yet been sufficiently investigated in all life stages. In the current study, we investigated cryodamage after vitrification/warming of neonatal ovaries from a nonhuman primate, the common marmoset (Callithrix jacchus). A Cryotop was used for cryopreservation of whole ovaries. The morphology of the vitrified/warmed ovaries was found to be equivalent to that of fresh ovaries. No significant difference in the number of oocytes retaining normal morphology per unit area in histological sections was found between the two groups. In an analysis of dispersed cells from the ovaries, however, the cell viability of the vitrified/warmed group tended to be decreased. The results of a comet assay showed no significant differences in DNA damage. These results show that cryopreservation of neonatal marmoset ovaries using vitrification may be useful as a storage system for whole ovaries. PMID:26876597

  16. Cryopreservation of ovaries from neonatal marmoset monkeys.

    PubMed

    Motohashi, Hideyuki H; Ishibashi, Hidetoshi

    2016-07-29

    The ovary of neonatal nonhuman primates contains the highest number of immature oocytes, but its cryopreservation has not yet been sufficiently investigated in all life stages. In the current study, we investigated cryodamage after vitrification/warming of neonatal ovaries from a nonhuman primate, the common marmoset (Callithrix jacchus). A Cryotop was used for cryopreservation of whole ovaries. The morphology of the vitrified/warmed ovaries was found to be equivalent to that of fresh ovaries. No significant difference in the number of oocytes retaining normal morphology per unit area in histological sections was found between the two groups. In an analysis of dispersed cells from the ovaries, however, the cell viability of the vitrified/warmed group tended to be decreased. The results of a comet assay showed no significant differences in DNA damage. These results show that cryopreservation of neonatal marmoset ovaries using vitrification may be useful as a storage system for whole ovaries. PMID:26876597

  17. [Laparoscopic fenestration of the ovaries].

    PubMed

    Nalbanski, B; Pŭnevska, M; Veltova, L

    1997-01-01

    The authors have performed an ovary fenestration in 220 women with primary or secondary amenorrhea. This was made with the help of instrumentation for laparoscopy and a monopolar electrodiathermic coagulator with differently shaped endings. The power supply was provided from Martin Elektrotom 2000. A spontaneous recovers of the menstruation was achieved in 36.84% of the cases as a result of the endoscopic intervention. A follows up pregnancy was achieved in 12.4% of the women. Considering the obtained results, the authors recommend the use of a laparoscopic ovary fenestration when a women with ovarian cysts is treated. PMID:9471896

  18. Polycystic Ovary Syndrome, Obesity, and Pregnancy.

    PubMed

    Joham, Anju E; Palomba, Stefano; Hart, Roger

    2016-03-01

    Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting up to one in five reproductive-aged women. It is underpinned by insulin resistance and hyperandrogenism and is associated with metabolic, reproductive, and psychological features. Women with PCOS have higher rates of obesity and central adiposity compared with women without PCOS, and weight strongly influences prevalence and clinical severity of PCOS. Women with PCOS may have subfertility and women should be aware of factors affecting fertility, in particular the impact of obesity and age. Once pregnant, women with PCOS have significantly increased risk of pregnancy-related complications including gestational diabetes, hypertensive disorders, premature delivery, and delivery by cesarean section. The offspring of women with PCOS may have increased risk of congenital abnormalities and hospitalization in childhood. Clinicians should be aware of the increased risk and screen, prevent, and manage accordingly. PMID:26854709

  19. Genomics in mammalian cell culture bioprocessing

    PubMed Central

    Wuest, Diane M.; Harcum, Sarah W.; Lee, Kelvin H.

    2013-01-01

    Explicitly identifying the genome of a host organism including sequencing, mapping, and annotating its genetic code has become a priority in the field of biotechnology with aims at improving the efficiency and understanding of cell culture bioprocessing. Recombinant protein therapeutics, primarily produced in mammalian cells, constitute a $108 billion global market. The most common mammalian cell line used in biologic production processes is the Chinese hamster ovary (CHO) cell line, and although great improvements have been made in titer production over the past 25 years, the underlying molecular and physiological factors are not well understood. Confident understanding of CHO bioprocessing elements (e.g. cell line selection, protein production, and reproducibility of process performance and product specifications) would significantly improve with a well understood genome. This review describes mammalian cell culture use in bioprocessing, the importance of obtaining CHO cell line genetic sequences, and the current status of sequencing efforts. Furthermore, transcriptomic techniques and gene expression tools are presented, and case studies exploring genomic techniques and applications aimed to improve mammalian bioprocess performance are reviewed. Finally, future implications of genomic advances are surmised. PMID:22079893

  20. Value of ultrasonography in the diagnosis of polycystic ovary syndrome – literature review

    PubMed Central

    Abdalla, Nebil; Cendrowski, Krzysztof; Sawicki, Włodzimierz

    2015-01-01

    Polycystic ovary syndrome is a multi-factorial disease. Its etiopathogenesis has not been elucidated in detail. It is the most common endocrine disorder in women of child-bearing age. This disease entity is primarily characterized by disrupted ovulation and hyperandrogenism, but the clinical picture can be diversified and symptom intensity can vary. Currently, the sonographic assessment of ovaries is one of the obligatory criteria for the diagnosis of PCOS according to the Rotterdam consensus (2003) and Androgen Excess & PCOS Society (2006). This criterion is determined by the presence of ≥12 follicles within the ovary with a diameter of 2–9 mm and/or ovarian volume ≥10 cm3. Such an ultrasound image in one gonad only is sufficient to define polycystic ovaries. The coexistence of polycystic ovaries with polycystic ovary syndrome is confirmed in over 90% of cases irrespective of ethnic factors or race. However, because of the commonness of ultrasound features of polycystic ovaries in healthy women, the inclusion of this sign to the diagnostic criteria of polycystic ovary syndrome is still questioned. The development of new technologies has an undoubted influence on the percentage of diagnosed polycystic ovaries. This process has caused an increase in the percentage of polycystic ovary diagnoses since the Rotterdam criteria were published. It is therefore needed to prepare new commonly accepted diagnostic norms concerning the number of ovarian follicles and the standardization of the technique in which they are counted. The assessment of anti-Müllerian hormone levels as an equivalent of ultrasound features of polycystic ovaries is a promising method. However, analytic methods have to be standardized in order to establish commonly accepted diagnostic norms. PMID:26807298

  1. Value of ultrasonography in the diagnosis of polycystic ovary syndrome - literature review.

    PubMed

    Bachanek, Michał; Abdalla, Nebil; Cendrowski, Krzysztof; Sawicki, Włodzimierz

    2015-12-01

    Polycystic ovary syndrome is a multi-factorial disease. Its etiopathogenesis has not been elucidated in detail. It is the most common endocrine disorder in women of child-bearing age. This disease entity is primarily characterized by disrupted ovulation and hyperandrogenism, but the clinical picture can be diversified and symptom intensity can vary. Currently, the sonographic assessment of ovaries is one of the obligatory criteria for the diagnosis of PCOS according to the Rotterdam consensus (2003) and Androgen Excess & PCOS Society (2006). This criterion is determined by the presence of ≥12 follicles within the ovary with a diameter of 2-9 mm and/or ovarian volume ≥10 cm(3). Such an ultrasound image in one gonad only is sufficient to define polycystic ovaries. The coexistence of polycystic ovaries with polycystic ovary syndrome is confirmed in over 90% of cases irrespective of ethnic factors or race. However, because of the commonness of ultrasound features of polycystic ovaries in healthy women, the inclusion of this sign to the diagnostic criteria of polycystic ovary syndrome is still questioned. The development of new technologies has an undoubted influence on the percentage of diagnosed polycystic ovaries. This process has caused an increase in the percentage of polycystic ovary diagnoses since the Rotterdam criteria were published. It is therefore needed to prepare new commonly accepted diagnostic norms concerning the number of ovarian follicles and the standardization of the technique in which they are counted. The assessment of anti-Müllerian hormone levels as an equivalent of ultrasound features of polycystic ovaries is a promising method. However, analytic methods have to be standardized in order to establish commonly accepted diagnostic norms. PMID:26807298

  2. APOPTOSIS IN WHOLE MOUSE OVARIES

    EPA Science Inventory

    Apoptosis in Whole Mouse Ovaries
    Robert M. Zucker Susan C. Jeffay and Sally D. Perreault
    Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, 27711.

  3. Polycystic ovary syndrome and prolactinoma association.

    PubMed

    Yavasoglu, Irfan; Kucuk, Mert; Coskun, Adil; Guney, Engin; Kadikoylu, Gurhan; Bolaman, Zahit

    2009-01-01

    Hyperprolactinemia is the most common pituitary hormone hypersecretion syndrome in both men and women. Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting 5%-10% of reproductive age women. Here, we present a patient with irregular menses, obesity, hirsutism and infertility, and hyperprolactinemia who was diagnosed as PCOS and prolactinoma and admitted to our clinic. Prolactinoma and PCOS association is a rare condition. This 33-year-old woman was admitted to the internal medicine outpatient clinic for irregular menses, obesity, hirsutism and infertility, and hyperprolactinemia. Her laboratory results were as follows: prolactin was 74 ng/mL (normal range:1.8-20.3 ng/mL). Pelvic ultrasonography was correlated with polycystic ovary syndrome. Pituitary MRI showed 6x8 mm microadenoma at left half. Bromocriptine was started with 1.25 mg/day and increased to 5 mg/day. After six months of bromocriptine treatment her prolactin level was normal and no adenoma was detected in pituitary MRI. PCOS and prolactinoma association should be taken into account in PCOS cases with mild hyperprolactinoma. PMID:19367058

  4. Experimental evidence showing that no mitotically active female germline progenitors exist in postnatal mouse ovaries

    PubMed Central

    Zhang, Hua; Zheng, Wenjing; Shen, Yan; Adhikari, Deepak; Ueno, Hiroo; Liu, Kui

    2012-01-01

    It has been generally accepted for more than half a century that, in most mammalian species, oocytes cannot renew themselves in postnatal or adult life, and that the number of oocytes is already fixed in fetal or neonatal ovaries. This assumption, however, has been challenged over the past decade. In this study, we have taken an endogenous genetic approach to this question and generated a multiple fluorescent Rosa26rbw/+;Ddx4-Cre germline reporter mouse model for in vivo and in vitro tracing of the development of female germline cell lineage. Through live cell imaging and de novo folliculogenesis experiments, we show that the Ddx4-expressing cells from postnatal mouse ovaries did not enter mitosis, nor did they contribute to oocytes during de novo folliculogenesis. Our results provide evidence that supports the traditional view that no postnatal follicular renewal occurs in mammals, and no mitotically active Ddx4-expressing female germline progenitors exist in postnatal mouse ovaries. PMID:22778414

  5. Calcitriol attenuates cardiac remodeling and dysfunction in a murine model of polycystic ovary syndrome.

    PubMed

    Gao, Ling; Cao, Jia-Tian; Liang, Yan; Zhao, Yi-Chao; Lin, Xian-Hua; Li, Xiao-Cui; Tan, Ya-Jing; Li, Jing-Yi; Zhou, Cheng-Liang; Xu, Hai-Yan; Sheng, Jian-Zhong; Huang, He-Feng

    2016-05-01

    Polycystic ovary syndrome (PCOS) is a complex reproductive and metabolic disorder affecting 10 % of reproductive-aged women, and is well associated with an increased prevalence of cardiovascular risk factors. However, there are few data concerning the direct association of PCOS with cardiac pathologies. The present study aims to investigate the changes in cardiac structure, function, and cardiomyocyte survival in a PCOS model, and explore the possible effect of calcitriol administration on these changes. PCOS was induced in C57BL/6J female mice by chronic dihydrotestosterone administration, as evidenced by irregular estrous cycles, obesity and dyslipidemia. PCOS mice progressively developed cardiac abnormalities including cardiac hypertrophy, interstitial fibrosis, myocardial apoptosis, and cardiac dysfunction. Conversely, concomitant administration of calcitriol significantly attenuated cardiac remodeling and cardiomyocyte apoptosis, and improved cardiac function. Molecular analysis revealed that the beneficial effect of calcitriol was associated with normalized autophagy function by increasing phosphorylation levels of AMP-activated protein kinase and inhibiting phosphorylation levels of mammalian target of rapamycin complex. Our findings provide the first evidence for the presence of cardiac remodeling in a PCOS model, and vitamin D supplementation may be a potential therapeutic strategy for the prevention and treatment of PCOS-related cardiac remodeling. PMID:26578366

  6. Hirsutism and acne in polycystic ovary syndrome.

    PubMed

    Archer, Johanna S; Chang, R Jeffrey

    2004-10-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality affecting reproductive age women. Population-based studies estimate a prevalence of 5-10% [Obstet Gynecol 101 (2003) 995; Aust N Z J Obstet Gynaecol 41 (2001) 202]. The clinical characteristics of PCOS include hyperandrogenism, chronic anovulation, insulin resistance and infertility. Hyperandrogenism is generally manifested as hirsutism and acne. Both these clinical symptoms are treated with similar drug therapies, including oral contraceptive pills (OCPs), topical medications or antiandrogens such as spironolactone, flutamide and finasteride, as well as topical medications. Recent studies have shown that lower doses of these medications are as efficacious as high doses and have the advantage of decreased cost and an improved side-effect profile. Although hirsutism and acne can be considered cosmetic in nature, they cause significant social embarrassment and emotional distress. Physicians should be sensitive to these issues and approach patients in a caring and sympathetic manner. PMID:15380144

  7. Polycystic ovary syndrome in the Indian Subcontinent.

    PubMed

    Allahbadia, Gautam N; Merchant, Rubina

    2008-01-01

    Polycystic ovary syndrome (PCOS) is a complex, multifaceted, heterogeneous disorder that affects approximately 5 to 10% of women of reproductive age. It is characterized by hyperandrogenism, polycystic ovaries, and chronic anovulation along with insulin resistance, hyperinsulinemia, abdominal obesity, hypertension, and dyslipidemia as frequent metabolic traits (metabolic syndrome) that culminate in serious long-term consequences such as type 2 diabetes mellitus, endometrial hyperplasia, and coronary artery disease. It is one of the most common causes of anovulatory infertility. However, the heterogeneous clinical features of PCOS may change throughout the life span, starting from adolescence to postmenopausal age, largely influenced by obesity and metabolic alterations, and the phenotype of women with PCOS is variable, depending on the ethnic background. The etiology of PCOS is yet to be elucidated; however, it is believed that in utero fetal programming may have a significant role in the development of PCOS phenotype in adult life. Though a woman may be genetically predisposed to developing PCOS, it is only the interaction of environmental factors (obesity) with the genetic factors that results in the characteristic metabolic and menstrual disturbances and the final expression of the PCOS phenotype. Irrespective of geographic locations, a rapidly increasing prevalence of polycystic ovarian insulin resistance syndrome, excess body fat, adverse body fat patterning, hypertriglyceridemia, and obesity-related disease, such as diabetes and cardiovascular disease, have been reported in Asian Indians, suggesting that primary prevention strategies should be initiated early in this ethnic group. In lieu of the epidemic increase in the prevalence of obesity and diabetes mellitus in most industrialized countries including China and India owing to Westernization, urbanization, and mechanization, and evidence suggesting a pathogenetic role of obesity in the development of PCOS

  8. Transcriptome Analysis of the Capra hircus Ovary

    PubMed Central

    Zhao, Zhong Quan; Wang, Li Juan; Sun, Xiao Wei; Zhang, Jiao Jiao; Zhao, Yong Ju; Na, Ri Su; Zhang, Jia Hua

    2015-01-01

    Background Capra hircus is an important economic livestock animal, and therefore, it is necessary to discover transcriptome information about their reproductive performance. In this study, we performed de novo transcriptome sequencing to produce the first transcriptome dataset for the goat ovary using high-throughput sequencing technologies. The result will contribute to research on goat reproductive performance. Method and Results RNA-seq analysis generated more than 38.8 million clean paired end (PE) reads, which were assembled into 80,069 unigenes (mean size = 619 bp). Based on sequence similarity searches, 64,824 (60.6%) genes were identified, among which 29,444 and 11,271 unigenes were assigned to Gene Ontology (GO) categories and Clusters of Orthologous Groups (COG), respectively. Searches in the Kyoto Encyclopedia of Genes and Genomes pathway database (KEGG) showed that 27,766 (63.4%) unigenes were mapped to 258 KEGG pathways. Furthermore, we investigated the transcriptome differences of goat ovaries at two different ages using a tag-based digital gene expression system. We obtained a sequencing depth of over 5.6 million and 5.8 million tags for the two ages and identified a large number of genes associated with reproductive hormones, ovulatory cycle and follicle. Moreover, many antisense transcripts and novel transcripts were found; clusters with similar differential expression patterns, enriched GO terms and metabolic pathways were revealed for the first time with regard to the differentially expressed genes. Conclusions The transcriptome provides invaluable new data for a functional genomic resource and future biological research in Capra hircus, and it is essential for the in-depth study of candidate genes in breeding programs. PMID:25822507

  9. Does ovary need D-chiro-inositol?

    PubMed Central

    2012-01-01

    Backgroud Polycystic Ovary Syndrome (PCOS) is a multifactorial pathology that affects 10% of the women in reproductive age being the main cause of infertility due to menstrual dysfunction. Since 1980, it is known that PCOS is associated with insulin resistance (IR). The recognition of this association has prompted extensive investigation on the relationship between insulin and gonadal function, and has turned insulin sensitizer agent as the main therapeutic choice. In particular two different polyalcohol myo-inositol and D-chiro-inositol have been shown to improve insulin resistance, hyperandrogenism and to induce ovulation in PCOS women. In particular, while data on myo-inositol and restored ovulation were consistent, data on D-chiro-inositol were not . Recently, a comparative study, proposed a D-chiro-inositol paradox in the ovary of PCOS patients hypothesizing that only myo-inositol has a specific ovarian action. In the present study we aim to further study the role played by D-chiro-inositol at ovarian level. Methods A total of 54 women, aged <40 years and diagnosed with PCOS were enrolled in this study. Patients with insulin resistance and/or hyperglycaemia were excluded from the study. Patients were randomly divided into 5 groups (n=10-12): a placebo group, and 4 groups (A-D) that received 300-600-1200-2400 mg of DCI daily respectively. All treatments were carried out for 8 weeks before follicle stimulating hormone (rFSH) administration. Results Total r-FSH units increased significantly in the two groups that received the higher doses of DCI. The number of immature oocytes was significantly increased in the three groups that received the higher doses of DCI. Concurrently, the number of MII oocytes was significantly lower in the D group compared to placebo group. Noteworthy, the number of grade I embryos was significantly reduced by DCI supplementation. Conclusions Indeed, increasing DCI dosage progressively worsens oocyte quality and ovarian response. PMID

  10. Changes in the content of sex steroid hormone receptors in the growing and regressing ovaries of Gallus domesticus during development.

    PubMed

    González-Morán, María Genoveva; González-Arenas, Aliesha; Germán-Castelán, Liliana; Camacho-Arroyo, Ignacio

    2013-08-01

    Sex steroids participate in the regulation of reproduction in female chickens. In this work, we determined the content of androgen receptor (AR), intracellular progesterone receptor isoforms (PR-A and PR-B), membrane progesterone receptor γ (mPRγ) and estrogen receptor α (ER-α) in the left growing and right regressing ovaries of Gallus domesticus from 13-day-old chicken embryos to 1-month-old chickens by western blot analysis. A marked difference in the morphological characteristics of the left and the right ovaries during development was observed. Results show a higher content of AR in the left ovary than in the right one in all ages. In the left ovary, the highest content of AR was observed on day 13 of embryonic development, and diminished with age. In the right ovary, AR was expressed from day 13 of embryonic development to 1-day-old, and became undetectable at 1-week and 1-month-old. In the left ovary, PR isoforms were not detected on day 13 of embryonic development, but they presented a marked expression after hatching. In the right ovary, the highest expression of both PR isoforms was found on 1-day-old, and significantly decreased with age. PR-B was the predominant isoform on 1-day and 1-month old in the left ovary, whereas PR-A was the predominant one on day 13 of embryonic development in the right ovary. Interestingly, mPRγ was detected at 1-week and 1-month-old in the left ovary meanwhile in the right ovary, it was detected from day 13 of embryonic development to 1-day-old. ER-α was only detected in the left ovary from day 13 to 1-week-old, while in 1-month-old chickens, it was expressed in both ovaries. In the left ovary, ER-α content was lower from 1-day to 1-month-old as compared with day 13 of embryonic development. Our results demonstrate a differential expression of sex steroid hormone receptors between the left growing and the right regressing ovary, and throughout chickens' age; and this is the first report about mPR expression in birds

  11. [Difficulties and pitfalls in the diagnosis of polycystic ovary syndrome].

    PubMed

    Marcondes, José Antonio Miguel; Barcellos, Cristiano Roberto Grimaldi; Rocha, Michelle Patrocínio

    2011-02-01

    The polycystic ovary syndrome is one of the most common endocrinopathies, affecting approximately 7% of women of reproductive age. Although it was described in 1935, only in 1990 was published the first Consensus regarding it its diagnosis. Today, the syndrome is also considered a cardiovascular risk factor, with a high prevalence of metabolic disorders. Reflecting this new vision of the syndrome, several documents, including Consensus, Statement and Guidelines have been published, addressing different aspects of the syndrome. This review is an analysis of documents obtained through a survey in the PubMed database, using the keywords "polycystic ovary syndrome", "hyperandrogenism" and "hirsutism", separately, taking as limiting the term Type of Article (Practice Guideline, Consensus Development Conference, Guideline) without limitation of time, language and age, having been selected only those documents prepared under the sponsorship of Medical Entities and with more than one author. PMID:21468515

  12. Contrast imaging ultrasound detects abnormalities in the marmoset ovary.

    PubMed

    Hastings, J M; Morris, K D; Allan, D; Wilson, H; Millar, R P; Fraser, H M; Moran, C M

    2012-12-01

    The development of a functional vascular tree within the primate ovary is critical for reproductive health. To determine the efficacy of contrast agents to image the microvascular environment within the primate ovary, contrast ultrasonography was performed in six reproductive-aged female common marmosets (Callithrix jacchus) during the late luteal phase of the cycle, following injection of Sonovue™. Regions of interest (ROIs), representing the corpus luteum (CL) and noncorpus luteum ovarian tissue (NCLOT), were selected during gray-scale B-mode ultrasound imaging. The magnitude of backscatter intensity of CL and NCLOT ROIs were calculated in XnView, post hoc: subsequent gamma-variate modeling was implemented in Matlab to determine perfusion parameters. Histological analysis of these ovaries revealed a total of 11 CL, nine of which were identified during contrast ultrasonography. The median enhancement ratio was significantly increased in the CL (5.54AU; 95% CI -2.21-68.71) compared to the NCLOT (2.82AU; 95% CI 2.73-15.06; P < 0.05). There was no difference in time parameters between the CL and NCLOT. An additional avascular ROI was identified in the ovary of Animal 5, both histologically and by ultrasonography. This cystic ROI displayed a markedly lower enhancement ratio (0.79AU) and higher time parameters than mean CL and NCLOT, including time to peak and time to wash out. These data demonstrate, for the first time, the ability of commercially available contrast agents, to differentiate structures within the nonhuman primate ovary. Contrast-enhanced ultrasonography has a promising future in reproductive medicine. PMID:22890799

  13. Cardiometabolic Aspects of the Polycystic Ovary Syndrome

    PubMed Central

    Tan, Bee K.; Weickert, Martin O.; Lois, Konstantinos; Nestler, John E.; Sattar, Naveed; Lehnert, Hendrik

    2012-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age and is associated with various metabolic perturbations, in addition to chronic anovulation and factors related to androgen excess. In general, women live longer than men and develop cardiovascular disease at an older age. However, women with PCOS, as compared with age- and body mass index-matched women without the syndrome, appear to have a higher risk of insulin resistance, hyperinsulinemia, glucose intolerance, dyslipidemia, and an increased prothrombotic state, possibly resulting in a higher rate of type 2 diabetes mellitus, fatty liver disease, subclinical atherosclerosis, vascular dysfunction, and finally cardiovascular disease and mortality. Further alterations in PCOS include an increased prevalence of sleep apnea, as well as various changes in the secretion and/or function of adipokines, adipose tissue-derived proinflammatory factors and gut hormones, all of them with direct or indirect influences on the complex signaling network that regulates metabolism, insulin sensitivity, and energy homeostasis. Reviews on the cardiometabolic aspects of PCOS are rare, and our knowledge from recent studies is expanding rapidly. Therefore, it is the aim of the present review to discuss and to summarize the current knowledge, focusing on the alterations of cardiometabolic factors in women with PCOS. Further insight into this network of factors may facilitate finding therapeutic targets that should ameliorate not only ovarian dysfunction but also the various cardiometabolic alterations related to the syndrome. PMID:22829562

  14. Apoptosis in mammalian oocytes: a review.

    PubMed

    Tiwari, Meenakshi; Prasad, Shilpa; Tripathi, Anima; Pandey, Ashutosh N; Ali, Irfan; Singh, Arvind K; Shrivastav, Tulsidas G; Chaube, Shail K

    2015-08-01

    Apoptosis causes elimination of more than 99% of germ cells from cohort of ovary through follicular atresia. Less than 1% of germ cells, which are culminated in oocytes further undergo apoptosis during last phases of oogenesis and depletes ovarian reserve in most of the mammalian species including human. There are several players that induce apoptosis directly or indirectly in oocytes at various stages of meiotic cell cycle. Premature removal of encircling granulosa cells from immature oocytes, reduced levels of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate, increased levels of calcium (Ca(2+)) and oxidants, sustained reduced level of maturation promoting factor, depletion of survival factors, nutrients and cell cycle proteins, reduced meiotic competency, increased levels of proapoptotic as well as apoptotic factors lead to oocyte apoptosis. The BH3-only proteins also act as key regulators of apoptosis in oocyte within the ovary. Both intrinsic (mitochondria-mediated) as well as extrinsic (cell surface death receptor-mediated) pathways are involved in oocyte apoptosis. BID, a BH3-only protein act as a bridge between both apoptotic pathways and its cleavage activates cell death machinery of both the pathways inside the follicular microenvironment. Oocyte apoptosis leads to the depletion of ovarian reserve that directly affects reproductive outcome of various mammals including human. In this review article, we highlight some of the important players and describe the pathways involved during oocyte apoptosis in mammals. PMID:25958165

  15. Obesity and polycystic ovary syndrome.

    PubMed

    Naderpoor, N; Shorakae, S; Joham, A; Boyle, J; De Courten, B; Teede, H J

    2015-03-01

    Obesity is now a major international health concern. It is increasingly common in young women with reproductive, metabolic and psychological health impacts. Reproductive health impacts are often poorly appreciated and include polycystic ovary syndrome (PCOS), infertility and pregnancy complications. PCOS is the most common endocrine condition in women and is underpinned by hormonal disturbances including insulin resistance and hyperandrogenism. Obesity exacerbates hormonal and clinical features of PCOS and women with PCOS appear at higher risk of obesity, with multiple underlying mechanisms linking the conditions. Lifestyle intervention is first line in management of PCOS to both prevent weight gain and induce weight loss; however improved engagement and sustainability remain challenges with the need for more research. Medications like metformin, orlistat, GLP1 agonists and bariatric surgery have been used with the need for large scale randomised clinical trials to define their roles. PMID:25411807

  16. Exploring mechanisms of sex differences in longevity: lifetime ovary exposure and exceptional longevity in dogs.

    PubMed

    Waters, David J; Kengeri, Seema S; Clever, Beth; Booth, Julie A; Maras, Aimee H; Schlittler, Deborah L; Hayek, Michael G

    2009-12-01

    To move closer to understanding the mechanistic underpinnings of sex differences in human longevity, we studied pet dogs to determine whether lifetime duration of ovary exposure was associated with exceptional longevity. This hypothesis was tested by collecting and analyzing lifetime medical histories, age at death, and cause of death for a cohort of canine 'centenarians'--exceptionally long-lived Rottweiler dogs that lived more than 30% longer than average life expectancy for the breed. Sex and lifetime ovary exposure in the oldest-old Rottweilers (age at death, > or = 13 years) were compared to a cohort of Rottweilers that had usual longevity (age at death, 8.0-10.8 years). Like women, female dogs were more likely than males to achieve exceptional longevity (OR, 95% CI = 2.0, 1.2-3.3; P = 0.006). However, removal of ovaries during the first 4 years of life erased the female survival advantage. In females, a strong positive association between ovaries and longevity persisted in multivariate analysis that considered other factors, such as height, body weight, and mother with exceptional longevity. A beneficial effect of ovaries on longevity in females could not be attributed to resistance against a particular disease or major cause of death. Our results document in dogs a female sex advantage for achieving exceptional longevity and show that lifetime ovary exposure, a factor not previously evaluated in women, is associated with exceptional longevity. This work introduces a conceptual framework for designing additional studies in pet dogs to define the ovary-sensitive biological processes that promote healthy human longevity. PMID:19732047

  17. Optimizing transient recombinant protein expression in mammalian cells.

    PubMed

    Hopkins, Ralph F; Wall, Vanessa E; Esposito, Dominic

    2012-01-01

    Transient gene expression (TGE) in mammalian cells has become a routine process for expressing recombinant proteins in cell lines such as human embryonic kidney 293 and Chinese hamster ovary cells. The rapidly increasing need for recombinant proteins requires further improvements in TGE technology. While a great deal of focus has been directed toward optimizing the secretion of antibodies and other naturally secreted targets, much less work has been done on ways to improve cytoplasmic expression in mammalian cells. The benefits to protein production in mammalian cells, particularly for eukaryotic proteins, should be very significant - glycosylation and other posttranslational modifications will likely be native or near-native, solubility and protein folding would likely improve overexpression in heterologous hosts, and expression of proteins in their proper intracellular compartments is much more likely to occur. Improvements in this area have been slow, however, due to limited development of the cell culture processes needed for low-cost, higher-throughput expression in mammalian cells, and the relatively low diversity of DNA vectors for protein production in these systems. Here, we describe how the use of recombinational cloning, coupled with improvements in transfection protocols which increase speed and lower cost, can be combined to make mammalian cells much more amenable for routine recombinant protein expression. PMID:21987258

  18. Histological evaluation of rat larynx in experimental polycystic ovary syndrome model.

    PubMed

    Deveci, Hande Senem; Deveci, Ildem; Habesoglu, Mehmet; Sürmeli, Mehmet; Kınıs, Vefa; Eriman, Murat; Gunes, Pembegul; Yekrek, Murat; Egeli, Erol

    2012-08-01

    This study aimed at studying the histopathological effects of hyperandrogenemia and estrogen deficiency on larynx mucosa in experimentally designed polycystic ovary syndrome of female rats. Two groups of experimental polycystic ovary syndrome model were composed in healthy female rats by per oral letrozole administration of for 21 and 42 days. Also a control group which only took vehicle (saline) for 42 days was designed. Laryngeal mucosa and ovaries of all animals were examined histopathologically by light microscopy and the serum hormone levels were analyzed using a solid-phase, two-site chemiluminescent enzyme immunometric assay. Statistically significant edema, vascular engorgement, inflammation, cilia loss and differentiation of goblet cell distribution were observed when the control group and study groups were compared (p < 0.01). In serum hormonal analysis there was a significant increase in levels of androgens and decrease in levels of estrogens. In addition, polycystic appearance of ovaries in letrozole-administered groups and normal appearance of ovaries in control group have been proven histopathologically. Polycystic ovary syndrome which causes estrogen deficiency and hyperandrogenemia in fertile ages resulted in histopathological changes in laryngeal mucosa. PMID:22407189

  19. Clinical characteristics in Taiwanese women with polycystic ovary syndrome

    PubMed Central

    2015-01-01

    Polycystic ovary syndrome (PCOS) is one of the most common hormonal endocrine disorders in women of reproductive age. It consists of a heterogeneous collection of signs and symptoms that together form a disorder spectrum. The diagnosis of PCOS is principally based on clinical and physical findings. The extent of metabolic abnormalities in women with PCOS varies with phenotype, body weight, age, and ethnicity. For general population, the prevalence of hyperandrogenism and oligomenorrhea decreases with age, while complications such as insulin resistance and other metabolic disturbances increase with age. Obese women with PCOS have a higher risk of developing oligomenorrhea, amenorrhea, hyperandrogenemia, insulin resistance, and lower luteinizing hormone (LH) to follicle stimulation hormone (FSH) ratios than non-obese women with PCOS. The LH to FSH ratio is a valuable diagnostic tool in evaluating Taiwanese women with PCOS, especially in the diagnosis of oligomenorrhea. Overweight/obesity is the major determinant of cardiovascular and metabolic disturbances in women of reproductive age. PMID:26473107

  20. Novel expression and functional role of ghrelin in chicken ovary.

    PubMed

    Sirotkin, A V; Grossmann, R; María-Peon, M T; Roa, J; Tena-Sempere, M; Klein, S

    2006-09-26

    Ghrelin has recently emerged as pleiotropic regulator of a wide array of endocrine and non-endocrine functions. The former likely includes the control of gonadal function, as expression of ghrelin and its putative receptor, the GH secretagogue receptor type 1a (GHS-R1a), has been described in mammalian gonads, and direct effects of ghrelin in the control of testicular secretion and cell proliferation have been reported. Yet, the expression and/or functional role of ghrelin in gonads from non-mammalian species remain to be analyzed. The present study aimed to evaluate the expression of ghrelin and GHS-R genes in the chicken ovary, and to assess the potential involvement of ghrelin in the direct control of chick ovarian function. To this end, RT-PCR assays for ghrelin and GHS-R1a mRNAs were performed in ovarian tissue, and cultures of chicken ovarian cells were conducted in the presence of increasing doses (1, 10 or 100 ng/ml) of the ghrelin analog, ghrelin 1-18. Our results demonstrate that both ghrelin and GHS-R1a mRNAs are expressed in chick ovarian tissue. Moreover, challenge of ovarian granulosa cells with ghrelin 1-18 was able to induce markers of proliferation (i.e. expression of both PCNA and cyclin), and to modulate markers of apoptosis (i.e. decreased expression of caspase-3, bax, bcl-2 and TUNEL-positive cells). Moreover, ghrelin 1-18 increased the expression of PCNA, cyclin, bax and p53 in cultures of ovarian follicular fragments, where it also stimulated the release of progesterone, estradiol, arginine-vasotocin (AVT) and IGF-I, but not of testosterone. In conclusion, our study provides novel evidence for the gonadal expression of the genes encoding ghrelin and its cognate receptor in a non-mammalian species, i.e. the chicken ovary, and unravels the potential involvement of this newly discovered molecule in the control of key gonadal functions in the chick, such as proliferation, apoptosis, and hormone release. PMID:16891055

  1. Laparoscopic management of tumor in supernumerary ovary

    PubMed Central

    Prakash, Ved; Kant, Anita; Parashar, Abha; Rani, Uma

    2016-01-01

    Laparoscopic management of most of the adnexal masses has become feasible in the present era of advancing endoscopic techniques. A postmenopausal lady presented with lump in the abdomen, appeared to be a solid ovarian mass on ultrasound, and magnetic resonance imaging. On laparoscopy, both the ovaries were normal and the mass was not connected to uterus or adnexa. The mass was removed and histopathology confirmed it to be ovarian tissue thus confirming it to be a tumor in a supernumerary ovary. Examples of supernumerary ovary are among the rarest of gynecological abnormalities. PMID:27134478

  2. Laparoscopic management of tumor in supernumerary ovary.

    PubMed

    Prakash, Ved; Kant, Anita; Parashar, Abha; Rani, Uma

    2016-01-01

    Laparoscopic management of most of the adnexal masses has become feasible in the present era of advancing endoscopic techniques. A postmenopausal lady presented with lump in the abdomen, appeared to be a solid ovarian mass on ultrasound, and magnetic resonance imaging. On laparoscopy, both the ovaries were normal and the mass was not connected to uterus or adnexa. The mass was removed and histopathology confirmed it to be ovarian tissue thus confirming it to be a tumor in a supernumerary ovary. Examples of supernumerary ovary are among the rarest of gynecological abnormalities. PMID:27134478

  3. White spotting variant (Wv) mouse as an experimental model for ovarian aging and menopausal biology

    PubMed Central

    Smith, Elizabeth R.; Yeasky, Toni; Wei, Jain Qin; Miki, Roberto A.; Cai, Kathy Q.; Smedberg, Jennifer L.; Yang, Wan-Lin; Xu, Xiang-Xi

    2011-01-01

    Objective Menopause is a unique phenomenon in modern women, as most mammalian species possess a reproductive period comparable to their lifespan. Menopause is caused by the depletion of germ cell-containing ovarian follicles, and in laboratory studies is usually modeled in animals in which the ovarian function is removed by ovariectomy or chemical poisoning of the germ cells. Our objective was to explore and characterize the white spotting variant (Wv) mice that have reduced ovarian germ cell abundance, a result of a point mutation in the c-kit gene that decreases the kinase activity, as a genetic model for use in menopausal studies. Methods Physiological and morphological features associated with menopause were determined in female Wv/Wv mice compared to age-matched wildtype controls. Immunohistochemistry was used to evaluate the presence and number of follicles in paraffin-embedded ovaries. Bone density and body composition were evaluated using the PIXImus X-ray densitometer, and lipids, calcium, and hormone levels were determined in serum using antigen-specific EIAs. Heart and body weight were measured, and cardiac function was evaluated by transthoracic echocardiography. Results The ovaries of the Wv/Wv females have a greatly reduced number of normal germ cells at birth compared to wildtype mice. The remaining follicles are depleted by around 2 months, and the ovaries develop benign epithelial lesions that resemble morphological changes that occur during ovarian aging, whereas a normal mouse ovary has numerous follicles at all stages of development and retains some follicles even in advanced age. Wv mice have elevated plasma gonadotrophins and reduced estrogen and progesterone levels, a significant reduction in bone mass density, and elevated serum cholesterol and lipoprotein levels. Moreover, the Wv female mice have enlarged hearts and reduced cardiac function. Conclusions The reduction of c-kit activity in Wv mice leads to a substantially diminished

  4. MiR-125b Regulates Primordial Follicle Assembly by Targeting Activin Receptor Type 2a in Neonatal Mouse Ovary.

    PubMed

    Wang, Shufen; Liu, Jiali; Li, Xinqiang; Ji, Xiaowen; Zhang, Jianfang; Wang, Yue; Cui, Sheng

    2016-04-01

    The establishment of the primordial follicle pool is crucial for fertility in mammalian females, and the interruption of overall micro-RNA production byDicer1conditional knockout in the female reproductive system results in infertility. However, there are few reports about the functions of individual micro-RNA in regulating primordial follicle assembly. The present study aimed to investigate the function of miR-125b, which is conserved and preferentially expressed in mammalian ovary during primordial follicle assembly. Detection of miR-125b in the developing mouse ovaries by real-time PCR and in situ hybridization showed that it was highly expressed perinatally and specifically located in the ovarian somatic cells. MiR-125b overexpression blocked the process of primordial follicle assembly in cultured newborn mouse ovaries, while its knockdown promoted this process. Further studies showed that miR-125b regulated the activin/Smad2 signaling in neonatal mouse ovary by directly targeting the 3'-untranslated region of activin receptor type 2a (Acvr2a). Overexpression of miR-125b in neonatal mouse ovary suppressed theAcvr2aprotein level, attenuating activin/Smad2 signaling, while knockdown of miR-125b showed the opposite effects. In addition, recombinant human activin A (rh-ActA) down-regulated miR-125b in the neonatal mouse ovary. Overexpression of miR-125b attenuated the promoting effects of rh-ActA on primordial follicle assembly. Taken together, these data suggest that miR-125b blocks the process of primordial follicle assembly, and miR-125b may play this role by regulating the expression ofAcvr2ain the activin/Smad2 signaling pathway. PMID:26962113

  5. Measurement of Bluetongue Virus Binding to a Mammalian Cell Surface Receptor by an In Situ Immune Fluorescent Staining Technique

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A quantifiable in situ immune fluorescent assay (IFA) was developed to measure bluetongue virus (BTV) binding to mammalian cells. The utility of the assay was demonstrated with both Chinese hamster ovary (CHO) and bovine pulmonary artery endothelial (CPAE) cells. Since heparin sulfate (HS) has been ...

  6. Changes in the cellular localization of estrogen receptor alpha in the growing and regressing ovaries of Gallus domesticus during development.

    PubMed

    González-Morán, María Genoveva

    2014-04-25

    In this work, the presence of estrogen receptor alpha (ER-α) was determined in different cell subpopulations in the left growing and right regressing ovaries of Gallus domesticus from 13-day-old chicken embryos to one-month-old chickens by immunohistochemistry. Results revealed positive ER-α immunostaining in both ovaries during development, but the percentage, staining intensity, and cellular distribution of ER-α immunostaining changes according to whether it is the left or right ovary and with the animal's age. In the left ovary, the ER-α was localized in the nuclei of the germinal epithelium and in germ cells of the ovarian cortex, as well as in the interstitial cells, undifferentiated cells, and epithelial cells of the lacunar channels of the ovarian medulla in all ages. In contrast, in the right ovary from 13-day-old chicken embryos to one-week-old chickens, only the epithelial cells of lacunar channels were ER-α immunoreactive, but in the right ovary of one-month-old chickens both the epithelial cells of lacunar channels and the interstitial cells presented ER-α. These results demonstrate differential expression of ER-α in both chicken ovaries during development in a cell type-specific distribution, suggesting that these differences may be regarded as an important cause in the process of asymmetric ovarian development in the chicken. PMID:24704443

  7. Pregnancy complications in polycystic ovary syndrome patients.

    PubMed

    Katulski, Krzysztof; Czyzyk, Adam; Podfigurna-Stopa, Agnieszka; Genazzani, Andrea R; Meczekalski, Blazej

    2015-02-01

    Infertility is a widely disputed problem affecting patients suffering from polycystic ovary syndrome (PCOS). As a serious dysfunction, it frequently occurs in PCOS patients. It is, therefore, important to devote more attention to pregnancy in PCOS sufferers. According to various data, the risk of miscarriage in PCOS women is three times higher than the risk of miscarriage in healthy women. Unfortunately, the risk of most frequent pregnancy pathologies is also higher for PCOS patients, as gestational diabetes (GD), pregnancy-induced hypertension and pre-eclampsia, and small for gestational age (SGA) children. Impaired glucose tolerance and GD in pregnant PCOS patients occur more frequently than in healthy women. A quadruple increase in the risk of pregnancy-induced hypertension linked to arterial wall stiffness has also been observed in PCOS patients. The risk of pre-eclampsia, the most severe of all complications, is also four times higher in those suffering from PCOS. Pre-eclampsia is also more frequent in patients presenting additional risk factors accompanying PCOS, such as obesity or GD. At that point, it should be mentioned that PCOS patients are under 2.5 higher risk of giving birth to SGA children than healthy women. It appears that SGA can be linked to insulin resistance and insulin-dependent growth dysfunction. Therefore, PCOS pregnant women are patients of special obstetrical care. PMID:25356655

  8. Polycystic Ovary Syndrome in the Pediatric Population

    PubMed Central

    2010-01-01

    Abstract Polycystic ovary syndrome (PCOS) is a common disorder characterized by hyperandrogenism and disordered gonadotropin secretion, often associated with insulin resistance. The syndrome, which modulates both hormonal and metabolic processes, is the most common endocrinopathy in reproductive-age women and increases a woman's risk of infertility, endometrial pathology, and cardiometabolic disease. As it is currently defined, PCOS most likely encompasses several distinct diseases with similar clinical phenotypes but different underlying pathophysiological processes. However, hyperandrogenism remains the syndrome's clinical hallmark. The clinical manifestations of PCOS often emerge during childhood or in the peripubertal years, suggesting that the syndrome is influenced by fetal programming and/or early postnatal events. However, given that the full clinical spectrum of PCOS does not typically appear until puberty, a “two-hit” hypothesis has been proposed: (1) a girl develops hyperandrogenism via one or more of many different potential mechanisms; (2) the preexisting hyperandrogenism subsequently disturbs the hypothalamic–pituitary–ovarian axis, resulting in ovulatory dysfunction and sustained hyperandrogenism. No consensus guidelines exist regarding the diagnosis and management of PCOS in the pediatric population; however, because the syndrome is a diagnosis of exclusion, the clinical evaluation of girls suspected of having PCOS is aimed at excluding other causes of androgen excess and menstrual dysfunction. For the syndrome's management, emphasis is placed on lifestyle and symptom-directed treatment. PMID:20939704

  9. Fetal programming of polycystic ovary syndrome.

    PubMed

    Gur, Esra Bahar; Karadeniz, Muammer; Turan, Guluzar Arzu

    2015-07-10

    Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects up to 6.8% of reproductive age women. Experimental research and clinical observations suggest that PCOS may originate in the very early stages of development, possibly even during intrauterine life. This suggests that PCOS is either genetically-transmitted or is due to epigenetic alterations that develop in the intrauterine microenvironment. Although familial cases support the role of genetic factors, no specific genetic pattern has been defined in PCOS. Several candidate genes have been implicated in its pathogenesis, but none can specifically be implicated in PCOS development. Hypotheses based on the impact of the intrauterine environment on PCOS development can be grouped into two categories. The first is the "thrifty" phenotype hypothesis, which states that intrauterine nutritional restriction in fetuses causes decreased insulin secretion and, as a compensatory mechanism, insulin resistance. Additionally, an impaired nutritional environment can affect the methylation of some specific genes, which can also trigger PCOS. The second hypothesis postulates that fetal exposure to excess androgen can induce changes in differentiating tissues, causing the PCOS phenotype to develop in adult life. This review aimed to examine the role of fetal programming in development of PCOS. PMID:26185601

  10. Fetal programming of polycystic ovary syndrome

    PubMed Central

    Gur, Esra Bahar; Karadeniz, Muammer; Turan, Guluzar Arzu

    2015-01-01

    Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects up to 6.8% of reproductive age women. Experimental research and clinical observations suggest that PCOS may originate in the very early stages of development, possibly even during intrauterine life. This suggests that PCOS is either genetically-transmitted or is due to epigenetic alterations that develop in the intrauterine microenvironment. Although familial cases support the role of genetic factors, no specific genetic pattern has been defined in PCOS. Several candidate genes have been implicated in its pathogenesis, but none can specifically be implicated in PCOS development. Hypotheses based on the impact of the intrauterine environment on PCOS development can be grouped into two categories. The first is the “thrifty” phenotype hypothesis, which states that intrauterine nutritional restriction in fetuses causes decreased insulin secretion and, as a compensatory mechanism, insulin resistance. Additionally, an impaired nutritional environment can affect the methylation of some specific genes, which can also trigger PCOS. The second hypothesis postulates that fetal exposure to excess androgen can induce changes in differentiating tissues, causing the PCOS phenotype to develop in adult life. This review aimed to examine the role of fetal programming in development of PCOS. PMID:26185601

  11. Producing Newborn Synchronous Mammalian Cells

    NASA Technical Reports Server (NTRS)

    Gonda, Steve R.; Helmstetter, Charles E.; Thornton, Maureen

    2008-01-01

    A method and bioreactor for the continuous production of synchronous (same age) population of mammalian cells have been invented. The invention involves the attachment and growth of cells on an adhesive-coated porous membrane immersed in a perfused liquid culture medium in a microgravity analog bioreactor. When cells attach to the surface divide, newborn cells are released into the flowing culture medium. The released cells, consisting of a uniform population of synchronous cells are then collected from the effluent culture medium. This invention could be of interest to researchers investigating the effects of the geneotoxic effects of the space environment (microgravity, radiation, chemicals, gases) and to pharmaceutical and biotechnology companies involved in research on aging and cancer, and in new drug development and testing.

  12. Cryopreservation and orthotopic transplantation of rat ovaries.

    PubMed

    Dorsch, Martina; Wedekind, Dirk

    2010-01-01

    The number of rat strains increased considerably in the last decade and will increase continuously during the next years. This requires enough space for maintaining vital strains and techniques for cryobanking, which can be applied not only in specialised rat resource centres but also in regular animal houses. Here we describe an easy and fast method for the cryopreservation and transplantation of frozen-thawed ovaries of the rat. With dimethyl sulfoxide as cryoprotectant rat ovaries can be stored at -196 degrees C for unlimited time. For revitalisation thawed ovaries have to be orthotopically transplanted into appropriate ovarectomised recipients. Reestablishment of the reproductive cycle in the recipients can be confirmed by vaginal cytology shortly after transplantation. The recipients are able to produce 2-3 litters after mating with males of an appropriate strain. Cyropreservation of ovaries thus can be considered a reliable method to preserve scientifically and economically important stocks and strains of rats that are currently not required. PMID:20013242

  13. Pituitary-ovary axis and ovarian reserve in fertile women with multiple sclerosis: A pilot study.

    PubMed

    Sepúlveda, Maria; Ros, Cristina; Martínez-Lapiscina, Elena H; Solà-Valls, Nuria; Hervàs, Mariona; Llufriu, Sara; La Puma, Delon; Casals, Elena; Blanco, Yolanda; Villoslada, Pablo; Graus, Francesc; Castelo-Branco, Camil; Saiz, Albert

    2016-04-01

    Since a decline in the ovary function might impact the reproductive potential in women with multiple sclerosis (MS), we investigated the pituitary-ovary axis and ovarian reserve, including anti-Müllerian hormone (AMH) levels and ultrasound imaging of the ovaries, of 25 relapsing-remitting MS patients and 25 age-matched healthy controls. Mean levels of pituitary-gonadal hormones and age-adjusted parameters of ovarian reserve markers were not significantly different between both groups. Patients with higher disease activity (annualized relapse rate >0.5; n=9) had significantly lower AMH levels, total antral follicle count and ovarian volume, than those with lower disease activity. The finding of poorer ovarian reserve associated with higher disease activity should be taken into consideration since it may negatively impact the reproductive prognosis. PMID:26362892

  14. [Mechanism of the development of permanent estrus in rats after transplantation of the ovaries into a low temperature medium].

    PubMed

    Vunder, P A; Smetanina, M D

    1983-03-01

    Autotransplantation of the ovaries to the ears of adult rats induces permanent estrus following 5-7 days. Autotransplantation of the ovaries beneath the renal capsules makes the sexual cycle return to normal after the same period. Autotransplantation of the ovaries to the ears of infantile rats brings about pubertas precox followed by normal sexual cycle. Permanent estrus ensues only after 4 months. Transplantation of the ovaries from infantile rats to adult ones and vice versa has shown that age-related differences in the alterations seen in the sexual cycle in response to gonadal transplantation to the ears are caused by age-related differences in the recipients, precisely by those in the cyclic center. PMID:6681996

  15. Mammalian cardiolipin biosynthesis.

    PubMed

    Mejia, Edgard M; Nguyen, Hieu; Hatch, Grant M

    2014-04-01

    Cardiolipin is a major phospholipid in mitochondria and is involved in the generation of cellular energy in the form of ATP. In mammalian and eukaryotic cells it is synthesized via the cytidine-5'-diphosphate-1,2-diacyl-sn-glycerol phosphate pathway. This brief review will describe some of the more recent studies on mammalian cardiolipin biosynthesis and provide an overview of regulation of cardiolipin biosynthesis. In addition, the important role that this key phospholipid plays in disease processes including heart failure, diabetes, thyroid hormone disease and the genetic disease Barth Syndrome will be discussed. PMID:24144810

  16. Lateralization of the connections of the ovary to the celiac ganglia in juvenile rats

    PubMed Central

    Morán, Carolina; Zarate, Fabiola; Morán, José Luis; Handal, Anabella; Domínguez, Roberto

    2009-01-01

    During the development of the female rat, a maturing process of the factors that regulate the functioning of the ovaries takes place, resulting in different responses according to the age of the animal. Studies show that peripheral innervation is one relevant factor involved. In the present study we analyzed the anatomical relationship between the neurons in the celiac-superior mesenteric ganglia (CSMG), and the right or left ovary in 24 or 28 days old female pre-pubertal rats. The participation of the superior ovarian nerve (SON) in the communication between the CSMG and the ovaries was analyzed in animals with unilateral section of the SON, previous to injecting true blue (TB) into the ovarian bursa. The animals were killed seven days after treatment. TB stained neurons were quantified at the superior mesenteric-celiac ganglia. The number of labeled neurons in the CSMG of rats treated at 28 days of age was significantly higher than those treated on day 24. At age 24 days, injecting TB into the right ovary resulted in neuron stains on both sides of the celiac ganglia; whereas, injecting the left side the stains were exclusively ipsilateral. Such asymmetry was not observed when the rats were treated at age of 28 days. In younger rats, sectioning the left SON resulted in significantly lower number of stained neurons in the left ganglia while sectioning the right SON did not modify the number of stained neurons. When sectioning of the SON was performed to 28 days old rats, no staining was observed. Present results show that the number and connectivity of post-ganglionic neurons of the CSMG connected to the ovary of juvenile female rats change as the animal mature; that the SON plays a role in this communication process as puberty approaches; and that this maturing process is different for the right or the left ovary. PMID:19460167

  17. Transforming Growth Factor-β Signaling Participates in the Maintenance of the Primordial Follicle Pool in the Mouse Ovary*

    PubMed Central

    Wang, Zheng-Pin; Mu, Xin-Yi; Guo, Meng; Wang, Yi-Jing; Teng, Zhen; Mao, Guan-Ping; Niu, Wan-Bao; Feng, Li-Zhao; Zhao, Li-Hua; Xia, Guo-Liang

    2014-01-01

    Physiologically, only a few primordial follicles are activated to enter the growing follicle pool each wave. Recent studies in knock-out mice show that early follicular activation depends on signaling from the tuberous sclerosis complex, the mammalian target of rapamycin complex 1 (mTORC1), phosphatase and tensin homolog deleted on chromosome 10, and phosphatidylinositol 3-kinase (PI3K) pathways. However, the manner in which these pathways are normally regulated, and whether or not TGF-β acts on them are poorly understood. So, this study aims to identify whether or not TGF-β acts on the process. Ovary organ culture experiments showed that the culture of 18.5 days post-coitus (dpc) ovaries with TGF-β1 reduced the total population of oocytes and activated follicles, accelerated oocyte growth was observed in ovaries treated with TGF-βR1 inhibitor 2-(5-chloro-2-fluorophenyl)pteridin-4-yl]pyridin-4-yl-amine (SD208) compared with control ovaries, the down-regulation of TGF-βR1 gene expression also activated early primordial follicle oocyte growth. We further showed that there was dramatically more proliferation of granulosa cells in SD208-treated ovaries and less proliferation in TGF-β1-treated ovaries. Western blot and morphological analyses indicated that TGF-β signaling manipulated primordial follicle growth through tuberous sclerosis complex/mTORC1 signaling in oocytes, and the mTORC1-specific inhibitor rapamycin could partially reverse the stimulated effect of SD208 on the oocyte growth and decreased the numbers of growing follicles. In conclusion, our results suggest that TGF-β signaling plays an important physiological role in the maintenance of the dormant pool of primordial follicles, which functions through activation of p70 S6 kinase 1 (S6K1)/ribosomal protein S6 (rpS6) signaling in mouse ovaries. PMID:24515103

  18. Transforming growth factor-β signaling participates in the maintenance of the primordial follicle pool in the mouse ovary.

    PubMed

    Wang, Zheng-Pin; Mu, Xin-Yi; Guo, Meng; Wang, Yi-Jing; Teng, Zhen; Mao, Guan-Ping; Niu, Wan-Bao; Feng, Li-Zhao; Zhao, Li-Hua; Xia, Guo-Liang

    2014-03-21

    Physiologically, only a few primordial follicles are activated to enter the growing follicle pool each wave. Recent studies in knock-out mice show that early follicular activation depends on signaling from the tuberous sclerosis complex, the mammalian target of rapamycin complex 1 (mTORC1), phosphatase and tensin homolog deleted on chromosome 10, and phosphatidylinositol 3-kinase (PI3K) pathways. However, the manner in which these pathways are normally regulated, and whether or not TGF-β acts on them are poorly understood. So, this study aims to identify whether or not TGF-β acts on the process. Ovary organ culture experiments showed that the culture of 18.5 days post-coitus (dpc) ovaries with TGF-β1 reduced the total population of oocytes and activated follicles, accelerated oocyte growth was observed in ovaries treated with TGF-βR1 inhibitor 2-(5-chloro-2-fluorophenyl)pteridin-4-yl]pyridin-4-yl-amine (SD208) compared with control ovaries, the down-regulation of TGF-βR1 gene expression also activated early primordial follicle oocyte growth. We further showed that there was dramatically more proliferation of granulosa cells in SD208-treated ovaries and less proliferation in TGF-β1-treated ovaries. Western blot and morphological analyses indicated that TGF-β signaling manipulated primordial follicle growth through tuberous sclerosis complex/mTORC1 signaling in oocytes, and the mTORC1-specific inhibitor rapamycin could partially reverse the stimulated effect of SD208 on the oocyte growth and decreased the numbers of growing follicles. In conclusion, our results suggest that TGF-β signaling plays an important physiological role in the maintenance of the dormant pool of primordial follicles, which functions through activation of p70 S6 kinase 1 (S6K1)/ribosomal protein S6 (rpS6) signaling in mouse ovaries. PMID:24515103

  19. The follicle-deplete mouse ovary produces androgen.

    PubMed

    Mayer, Loretta P; Devine, Patrick J; Dyer, Cheryl A; Hoyer, Patricia B

    2004-07-01

    The follicle-depleted postmenopausal ovary is enriched in interstitial cells that produce androgens. This study was designed to cause follicle depletion in mice using the industrial chemical, 4-vinylcyclohexene diepoxide (VCD), and characterize the steroidogenic capacity of cells in the residual ovarian tissue. From a dose-finding study, the optimal daily concentration of VCD was determined to be 160 mg/kg. Female B6C3F(1) immature mice were treated daily with vehicle control or VCD (160 mg kg(-1) day(-1), 15 days, i.p.). Ovaries were removed and processed for histological evaluation. On Day 15 following onset of treatment, primordial follicles were depleted and primary follicles were reduced to about 10% of controls. On Day 46, primary follicles were depleted and secondary and antral follicles were reduced to 0.7% and 2.6% of control, respectively. Seventy-five percent of treated mice displayed disruptions in estrous cyclicity. All treated mice were in persistent diestrus (acyclic) by Day 58. Plasma FSH levels were increased (P < 0.05) relative to controls on Day 37 and had plateaued by Day 100. Relative to age-matched cyclic controls, by Day 127, the significant differences in VCD-treated mice included reduced ovarian and uterine weights, elevated plasma LH and FSH, and reduced plasma progesterone and androstenedione. Furthermore, plasma 17beta-estradiol levels were nondetectable. Unlike controls, immunostaining for LH receptor, and the high density lipoprotein receptor (SR-BI), was diffuse in ovarian sections from VCD-treated animals. Ovaries from Day 120 control and VCD-treated animals were dissociated and dispersed cells were placed in culture. Cultured cells from ovaries of VCD-treated animals produced less LH-stimulated progesterone than control cells. Androstenedione production was nondetectable in cells from cyclic control animals. Conversely, cells from VCD-treated animals produced androstenedione that was doubled in the presence of insulin and LH (1 and

  20. Mast cells in mammalian brain.

    PubMed

    Dropp, J J

    1976-01-01

    Mast cells, which had until recently been believed to be not present in the mammalian brain, were studied in the brains of 29 mammalian species. Although there was considerable intraspecific and interspecific variation, mast cells were most numerous within the leptomeninges (especially in those overlying the cerebrum and the dorsal thalamus - most rodents, most carnivores, chimpanzees, squirrel monkeys and elephant), the cerebral cortex (most rodents, tiger, fox, chimpanzee, tarsier, and elephant) and in many nuclei of the dorsal thalamus (most rodents, tiger, lion, and fox). In some mammals, mast cells were also numerous in the stroma of the telencephalic choroid plexuses (chimpanzee, squirrel monkey), the putamen and the claustrum (chimpanzee), the subfornical organ (pack rat, tiger, chimpanzee), the olfactory peduncles (hooded rat, albino rat), the stroma of the diencephalic choroid plexus (lion, chimpanzee, squirrel monkey), the pineal organ (chimpanzee, squirrel monkey), some nuclei of the hypothalamus (tiger), the infundibulum (hooded rat, tiger, fox) the area postrema (pack rat, chinchilla, lion, spider monkey, chimpanzee, fox) and some nuclei and tracts of the metencephalon and the myelencephalon (tiger). Neither the sex of the animal nor electrolytic lesions made in the brains of some of the animals at various times prior to sacrifice appeared to effect the number and the distribution of mast cells. Age-related changes in mast cell number and distribution were detected in the albino rat. PMID:961335

  1. Aging

    PubMed Central

    Park, Dong Choon

    2013-01-01

    Aging is initiated based on genetic and environmental factors that operate from the time of birth of organisms. Aging induces physiological phenomena such as reduction of cell counts, deterioration of tissue proteins, tissue atrophy, a decrease of the metabolic rate, reduction of body fluids, and calcium metabolism abnormalities, with final progression onto pathological aging. Despite the efforts from many researchers, the progression and the mechanisms of aging are not clearly understood yet. Therefore, the authors would like to introduce several theories which have gained attentions among the published theories up to date; genetic program theory, wear-and-tear theory, telomere theory, endocrine theory, DNA damage hypothesis, error catastrophe theory, the rate of living theory, mitochondrial theory, and free radical theory. Although there have been many studies that have tried to prevent aging and prolong life, here we introduce a couple of theories which have been proven more or less; food, exercise, and diet restriction. PMID:24653904

  2. Aging.

    PubMed

    Park, Dong Choon; Yeo, Seung Geun

    2013-09-01

    Aging is initiated based on genetic and environmental factors that operate from the time of birth of organisms. Aging induces physiological phenomena such as reduction of cell counts, deterioration of tissue proteins, tissue atrophy, a decrease of the metabolic rate, reduction of body fluids, and calcium metabolism abnormalities, with final progression onto pathological aging. Despite the efforts from many researchers, the progression and the mechanisms of aging are not clearly understood yet. Therefore, the authors would like to introduce several theories which have gained attentions among the published theories up to date; genetic program theory, wear-and-tear theory, telomere theory, endocrine theory, DNA damage hypothesis, error catastrophe theory, the rate of living theory, mitochondrial theory, and free radical theory. Although there have been many studies that have tried to prevent aging and prolong life, here we introduce a couple of theories which have been proven more or less; food, exercise, and diet restriction. PMID:24653904

  3. The Polycystic Ovary Syndrome: An update on metabolic and hormonal mechanisms

    PubMed Central

    Dumitrescu, R; Mehedintu, C; Briceag, I; Purcarea, VL; Hudita, D

    2015-01-01

    Polycystic ovary syndrome (PCOs) is a public health important disease, affecting one in five women at reproductive age. The clinical implications include reproductive, metabolic and psychological features. This article reviews the literature data related to the new metabolic and hormonal mechanisms in PCOs. Recognizing the real diagnostic of PCOs, using the right criteria, is a challenge in current practice. PMID:25866568

  4. The polycystic ovary syndrome: an update on metabolic and hormonal mechanisms.

    PubMed

    Dumitrescu, R; Mehedintu, C; Briceag, I; Purcarea, V L; Hudita, D

    2015-01-01

    Polycystic ovary syndrome (PCOs) is a public health important disease, affecting one in five women at reproductive age. The clinical implications include reproductive, metabolic and psychological features. This article reviews the literature data related to the new metabolic and hormonal mechanisms in PCOs. Recognizing the real diagnostic of PCOs, using the right criteria, is a challenge in current practice. PMID:25866568

  5. Effects of level of nutrient intake and age on mammalian target of rapamycin, insulin, and insulin-like growth factor-1 gene network expression in skeletal muscle of young Holstein calves.

    PubMed

    Wang, P; Drackley, J K; Stamey-Lanier, J A; Keisler, D; Loor, J J

    2014-01-01

    The molecular mechanisms by which level of nutrient intake enhances skeletal muscle growth in young ruminants are not fully understood. We examined mammalian target of rapamycin (mTOR), insulin, and insulin-like growth factor-1 (IGF-1) gene network expression in semitendinosus muscle tissue of young male Holstein calves fed a conventional milk replacer plus conventional starter (CON) or an enhanced milk replacer plus high-protein starter (ENH) for 5 wk followed by a conventional starter or a high-protein starter until 10 wk of age. Feeding ENH led to greater concentration of plasma IGF-1 and leptin and greater carcass protein and fat mass throughout the study. Despite the greater plasma IGF-1 and protein mass at wk 5, calves fed ENH had lower expression of IGF1R, INSR, and RPS6KB1 but greater expression of IRS1 and PDPK1 in muscle tissue. Except for IGF1R expression, which did not differ at wk 10, these differences persisted at wk 10, suggesting a long-term effect of greater nutrient intake on physiological and molecular mechanisms. Components of mTOR complex (mTORC)1 and mTORC2 (RICTOR and RPTOR) and FOXO1 expression decreased by wk 10 regardless of diet. Overall, the present data revealed that greater nutrient intake throughout the milk-fed and early postweaning phase alters body mass composition partly by altering hormonal and molecular profiles of genes associated with glucose and amino acid signaling. Those networks may play a crucial role in coordinating neonatal muscle growth and metabolism in response to level of nutrient intake. PMID:24210480

  6. Sarcoma-like mural nodule in a borderline mucinous tumor of the ovary: A rare entity.

    PubMed

    Ghosh, Prithwijit; Saha, Kaushik; Bhowmik, Sourav

    2014-10-01

    Sarcoma-like mural nodule (SLMN) is a very uncommon and misleading benign entity which may be associated with benign, borderline or malignant mucinous neoplasm of the ovary. It should be distinguished from other malignant mural nodules with sarcoma, carcinosarcoma or anaplastic carcinoma for proper management. We report a rare case of SLMN in a borderline mucinous tumor of the ovary in a 30-year-old lady. In spite of having confusing histopathological features the final diagnosis was made depending on the younger age of the patient, well circumscription of the nodule, absence of vascular invasion and immunohistochemical profile. PMID:25540570

  7. Ovary cryopreservation and transplantation for fertility preservation.

    PubMed

    Silber, S J

    2012-02-01

    The aim of this review is to summarize the state-of-the-art of ovarian transplantation and cryopreservation. This field has progressed over the last half century from simple animal experiments to sophisticated application in humans. The initial poor results in humans began to improve when a series of nine monozygotic (MZ) twin pairs discordant for premature ovarian failure (POF) underwent ovary transplantation at one center. All of these fresh ovary transplants were successful, resulting in 11 healthy babies in 7 of the 9 recipients. The same surgical techniques were then applied to 3 frozen ovary tissue transplants, up to 14 years after the ovary had been frozen, resulting in 3 more healthy babies. Around the world, the number of healthy babies has now risen to 28. Even ovary allotransplantation is being attempted in the not so uncommon situation where a previous bone marrow donor is now willing to donate ovarian tissue to the same recipient. Recipients routinely reinitiated ovulatory menstrual cycles and normal Day 3 serum FSH levels by 4.5 months. Most conceived naturally (three of them twice or three times from the same graft). The duration of function of fresh ovarian grafts, contrary to initial expectations, indicated minimal oocyte loss from ischemia time. Grafts of just modest portions of ovarian tissue have lasted >7 years. In vitro studies suggest that vitrification of ovarian tissue may be an improvement over the 70% oocyte viability loss from slow freeze. PMID:22205727

  8. Mammalian Septins Nomenclature

    PubMed Central

    Macara, Ian G.; Baldarelli, Richard; Field, Christine M.; Glotzer, Michael; Hayashi, Yasuhide; Hsu, Shu-Chan; Kennedy, Mary B.; Kinoshita, Makoto; Longtine, Mark; Low, Claudia; Maltais, Lois J.; McKenzie, Louise; Mitchison, Timothy J.; Nishikawa, Toru; Noda, Makoto; Petty, Elizabeth M.; Peifer, Mark; Pringle, John R.; Robinson, Phillip J.; Roth, Dagmar; Russell, S.E. Hilary; Stuhlmann, Heidi; Tanaka, Manami; Tanaka, Tomoo; Trimble, William S.; Ware, Jerry; Zeleznik-Le, Nancy J.; Zieger, Barbara

    2002-01-01

    There are 10 known mammalian septin genes, some of which produce multiple splice variants. The current nomenclature for the genes and gene products is very confusing, with several different names having been given to the same gene product and distinct names given to splice variants of the same gene. Moreover, some names are based on those of yeast or Drosophila septins that are not the closest homologues. Therefore, we suggest that the mammalian septin field adopt a common nomenclature system, based on that adopted by the Mouse Genomic Nomenclature Committee and accepted by the Human Genome Organization Gene Nomenclature Committee. The human and mouse septin genes will be named SEPT1–SEPT10 and Sept1–Sept10, respectively. Splice variants will be designated by an underscore followed by a lowercase “v” and a number, e.g., SEPT4_v1. PMID:12475938

  9. Mammalian sweet taste receptors.

    PubMed

    Nelson, G; Hoon, M A; Chandrashekar, J; Zhang, Y; Ryba, N J; Zuker, C S

    2001-08-10

    The sense of taste provides animals with valuable information about the quality and nutritional value of food. Previously, we identified a large family of mammalian taste receptors involved in bitter taste perception (the T2Rs). We now report the characterization of mammalian sweet taste receptors. First, transgenic rescue experiments prove that the Sac locus encodes T1R3, a member of the T1R family of candidate taste receptors. Second, using a heterologous expression system, we demonstrate that T1R2 and T1R3 combine to function as a sweet receptor, recognizing sweet-tasting molecules as diverse as sucrose, saccharin, dulcin, and acesulfame-K. Finally, we present a detailed analysis of the patterns of expression of T1Rs and T2Rs, thus providing a view of the representation of sweet and bitter taste at the periphery. PMID:11509186

  10. Linkage of regulators of TGF-β activity in the fetal ovary to polycystic ovary syndrome.

    PubMed

    Hatzirodos, Nicholas; Bayne, Rosemary A; Irving-Rodgers, Helen F; Hummitzsch, Katja; Sabatier, Laetitia; Lee, Sam; Bonner, Wendy; Gibson, Mark A; Rainey, William E; Carr, Bruce R; Mason, Helen D; Reinhardt, Dieter P; Anderson, Richard A; Rodgers, Raymond J

    2011-07-01

    Although not often discussed, the ovaries of women with polycystic ovary syndrome (PCOS) show all the hallmarks of increased TGF-β activity, with increased amounts of fibrous tissue and collagen in the ovarian capsule or tunica albuginea and ovarian stroma. Recent studies suggest that PCOS could have fetal origins. Genetic studies of PCOS have also found linkage with a microsatellite located in intron 55 of the extracellular matrix protein fibrillin 3. Fibrillins regulate TGF-β bioactivity in tissues by binding latent TGF-β binding proteins. We therefore examined expression of fibrillins 1-3, latent TGF-β binding proteins 1-4, and TGF-β 1-3 in bovine and human fetal ovaries at different stages of gestation and in adult ovaries. We also immunolocalized fibrillins 1 and 3. The results indicate that TGF-β pathways operate during ovarian fetal development, but most important, we show fibrillin 3 is present in the stromal compartments of fetal ovaries and is highly expressed at a critical stage early in developing human and bovine fetal ovaries when stroma is expanding and follicles are forming. These changes in expression of fibrillin 3 in the fetal ovary could lead to a predisposition to develop PCOS in later life. PMID:21411746

  11. Rheotaxis guides mammalian sperm

    PubMed Central

    Miki, Kiyoshi; Clapham, David E

    2013-01-01

    Background In sea urchins, spermatozoan motility is altered by chemotactic peptides, giving rise to the assumption that mammalian eggs also emit chemotactic agents that guide spermatozoa through the female reproductive tract to the mature oocyte. Mammalian spermatozoa indeed undergo complex adaptations within the female (the process of capacitation) that are initiated by agents ranging from pH to progesterone, but these factors are not necessarily taxic. Currently, chemotaxis, thermotaxis, and rheotaxis have not been definitively established in mammals. Results Here, we show that positive rheotaxis, the ability of organisms to orient and swim against the flow of surrounding fluid, is a major taxic factor for mouse and human sperm. This flow is generated within 4 hours of sexual stimulation and coitus in female mice; prolactin-triggered oviductal fluid secretion clears the oviduct of debris, lowers viscosity, and generates the stream that guides sperm migration in the oviduct. Rheotaxic movement is demonstrated in capacitated and uncapacitated spermatozoa in low and high viscosity medium. Finally, we show that a unique sperm motion we quantify using the sperm head's rolling rate reflects sperm rotation that generates essential force for positioning the sperm in the stream. Rotation requires CatSper channels, presumably by enabling Ca2+ influx. Conclusions We propose that rheotaxis is a major determinant of sperm guidance over long distances in the mammalian female reproductive tract. Coitus induces fluid flow to guide sperm in the oviduct. Sperm rheotaxis requires rotational motion during CatSper channel-dependent hyperactivated motility. PMID:23453951

  12. Linkage of regulators of TGF-β activity in the fetal ovary to polycystic ovary syndrome

    PubMed Central

    Hatzirodos, Nicholas; Bayne, Rosemary A.; Irving-Rodgers, Helen F.; Hummitzsch, Katja; Sabatier, Laetitia; Lee, Sam; Bonner, Wendy; Gibson, Mark A.; Rainey, William E.; Carr, Bruce R.; Mason, Helen D.; Reinhardt, Dieter P.; Anderson, Richard A.; Rodgers, Raymond J.

    2011-01-01

    Although not often discussed, the ovaries of women with polycystic ovary syndrome (PCOS) show all the hallmarks of increased TGF-β activity, with increased amounts of fibrous tissue and collagen in the ovarian capsule or tunica albuginea and ovarian stroma. Recent studies suggest that PCOS could have fetal origins. Genetic studies of PCOS have also found linkage with a microsatellite located in intron 55 of the extracellular matrix protein fibrillin 3. Fibrillins regulate TGF-β bioactivity in tissues by binding latent TGF-β binding proteins. We therefore examined expression of fibrillins 1–3, latent TGF-β binding proteins 1–4, and TGF-β 1–3 in bovine and human fetal ovaries at different stages of gestation and in adult ovaries. We also immunolocalized fibrillins 1 and 3. The results indicate that TGF-β pathways operate during ovarian fetal development, but most important, we show fibrillin 3 is present in the stromal compartments of fetal ovaries and is highly expressed at a critical stage early in developing human and bovine fetal ovaries when stroma is expanding and follicles are forming. These changes in expression of fibrillin 3 in the fetal ovary could lead to a predisposition to develop PCOS in later life.—Hatzirodos, N., Bayne, R. A., Irving-Rodgers, H. F., Hummitzsch, K., Sabatier, L., Lee, S., Bonner, W., Gibson, M. A., Rainey, W. E., Carr, B. R., Mason, H. D., Reinhardt, D. P., Anderson, R. A., Rodgers, R. J. Linkage of regulators of TGF-β activity in the fetal ovary to polycystic ovary syndrome. PMID:21411746

  13. Drug Improves Birth Rates for Women with Ovary Disorder

    MedlinePlus

    ... therapy in increasing live births for women with polycystic ovary syndrome. Letrozole could provide a less expensive, more effective treatment for women with this syndrome. Polycystic ovary syndrome (PCOS) is a leading cause of female infertility. ...

  14. Expression and preliminary functional profiling of the let-7 family during porcine ovary follicle atresia.

    PubMed

    Cao, Rui; Wu, Wang Jun; Zhou, Xiao Long; Xiao, Peng; Wang, Yi; Liu, Hong Lin

    2015-04-01

    Most follicles in the mammalian ovary undergo atresia. Granulosa cell apoptosis is a hallmark of follicle atresia. Our previous study using a microRNA (miRNA) microarray showed that the let-7 microRNA family was differentially expressed during follicular atresia. However, whether the let-7 miRNA family members are related to porcine (Sus scrofa) ovary follicular apoptosis is unclear. In the current study, real-time quantitative polymerase chain reaction showed that the expression levels of let-7 family members in follicles and granulosa cells were similar to our microarray data, in which miRNAs let-7a, let-7b, let-7c, and let-7i were significantly decreased in early atretic and progressively atretic porcine ovary follicles compared with healthy follicles, while let-7g was highly expressed during follicle atresia. Furthermore, flow cytometric analysis and Hoechst33342 staining demonstrated that let-7g increased the apoptotic rate of cultured granulosa cells. In addition, let-7 target genes were predicted and annotated by TargetScan, PicTar, gene ontology and Kyoto encyclopedia of genes and genomes pathways. Our data provide new insight into the association between the let-7 miRNA family in granulosa cell programmed death. PMID:25824548

  15. Mammalian Sirtuins: Biological Insights and Disease Relevance

    PubMed Central

    Haigis, Marcia C.; Sinclair, David A.

    2010-01-01

    Aging is accompanied by a decline in the healthy function of multiple organ systems, leading to increased incidence and mortality from diseases such as type II diabetes mellitus, neurodegenerative diseases, cancer, and cardiovascular disease. Historically, researchers have focused on investigating individual pathways in isolated organs as a strategy to identify the root cause of a disease, with hopes of designing better drugs. Studies of aging in yeast led to the discovery of a family of conserved enzymes known as the sirtuins, which affect multiple pathways that increase the life span and the overall health of organisms. Since the discovery of the first known mammalian sirtuin, SIRT1, 10 years ago, there have been major advances in our understanding of the enzymology of sirtuins, their regulation, and their ability to broadly improve mammalian physiology and health span. This review summarizes and discusses the advances of the past decade and the challenges that will confront the field in the coming years. PMID:20078221

  16. Expression and localization of heterogeneous nuclear ribonucleoprotein K in mouse ovaries and preimplantation embryos.

    PubMed

    Zhang, Ping; Wang, Ningling; Lin, Xianhua; Jin, Li; Xu, Hong; Li, Rong; Huang, Hefeng

    2016-02-26

    Heterogeneous nuclear ribonucleoprotein K (hnRNP K), an evolutionarily conserved protein, is involved in several important cellular processes that are relevant to cell proliferation, differentiation, apoptosis, and cancer development. However, details of hnRNP K expression during mammalian oogenesis and preimplantation embryo development are lacking. The present study investigates the expression and cellular localization of K protein in the mouse ovaries and preimplantation embryos using immunostaining. We demonstrate, for the first time, that hnRNP K is abundantly expressed in the nuclei of mouse oocytes in primordial, primary and secondary follicles. In germ vesicle (GV)-stage oocytes, hnRNP K accumulates in the germinal vesicle in a spot distribution manner. After germinal vesicle breakdown, speckled hnRNP K is diffusely distributed in the cytoplasm. However, after fertilization, the K protein relocates into the female and male pronucleus and persists in the blastomere nuclei. Localization of K protein in the human ovary and ovarian granulosa cell tumor (GCT) was also investigated. Overall, this study provides important morphological evidence to better understand the possible roles of hnRNP K in mammalian oogenesis and early embryo development. PMID:26850853

  17. Management of Early Carcinoma of the Ovary

    PubMed Central

    Chapman, George W.

    1988-01-01

    Ovarian cancer represents a formidable challenge to physicians. Early symptoms are nonspecific, and are usually attributed to disorders of the upper gastrointestinal tract. Especially important is suspicion of this neoplasm in its early stage. This article discusses the epidemiology, clinical features, evaluation, and treatment of early carcinomas of the ovary. PMID:3071612

  18. Immunohistochemistry of Paraffin Sections from Mouse Ovaries.

    PubMed

    Akkoyunlu, Gokhan; Tepekoy, Filiz

    2016-01-01

    Immunohistochemistry (IHC) is an efficient technique to detect cellular localizations of the proteins in paraffin-embedded tissues. It allows specific proteins to be visualized by the interaction of antibodies with an enzyme-substrate-chromogen system. Here, we describe indirect immunohistochemistry method for paraffin-embedded mouse ovaries fixed with Bouin's Fixative. PMID:27557588

  19. Melatonin influence in ovary transplantation: systematic review.

    PubMed

    Shiroma, M E; Botelho, N M; Damous, L L; Baracat, E C; Soares-Jr, J M

    2016-01-01

    Melatonin is an indolamine produced by the pineal gland and it can exert a potent antioxidant effect. Its free radical scavenger properties have been used to advantage in different organ transplants in animal experiments. Several concentrations and administration pathways have been tested and melatonin has shown encouraging beneficial results in many transplants of organs such as the liver, lungs, heart, pancreas, and kidneys. The objective of the present study was to review the scientific literature regarding the use of melatonin in ovary transplantation. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was carried out using the Cochrane and Pubmed databases and employing the terms 'melatonin' AND 'ovary' AND 'transplantation.' After analysis, 5 articles were extracted addressing melatonin use in ovary transplants and involving 503 animals. Melatonin enhanced various graft aspects like morphology, apoptosis, immunological reaction, revascularization, oxidative stress, and survival rate. Melatonin's antioxidative and antiapoptotic properties seemingly produce positive effects on ovarian graft activity. Despite the promising results, further studies in humans need to be conducted to consolidate its use, as ovary transplantation for fertility preservation is gradually being moved from the experimental stage to a clinical setting. PMID:27287621

  20. Re-torsion of the ovaries.

    PubMed

    Hyttel, Trine E W; Bak, Geske S; Larsen, Solveig B; Løkkegaard, Ellen C L

    2015-03-01

    The increasing use of de-torsion of the ovaries may result in re-torsion. This review addresses risk of re-torsion and describes preventive strategies to avoid re-torsion in pre-menarcheal girls, and fertile and pregnant women. We clinically reviewed PubMed, Embase, Trip and Cochrane databases. The main outcome measures were re-torsion and viability of ovary with fixation measures. A total of 38 publications including 71 girls, 363 fertile women, and 69 pregnant women were found to be relevant. All studies were case reports or case series, sometimes with non-randomized controls. The studies show considerable heterogeneity in design, population, management and outcome. Only four studies included more than 50 cases. In pregnancy the risk of re-torsion was as high as 19.5-37.5%; among fertile women it was 28.6%. Most articles concluded that fixation of the ovaries to the pelvic sidewall or plication of the ovarian ligament after torsion may prevent re-torsion. In one case a girl experienced re-torsion after ovariopexy. Based on observational studies it seems that de-torsion and fixation of the ovary is a safe procedure that usually ensures maintenance of ovarian function and reduces the risk of recurrence, especially when there are no ovarian cysts or adnexal masses. PMID:25412114

  1. MicroRNAs Related to Polycystic Ovary Syndrome (PCOS)

    PubMed Central

    Sørensen, Anja Elaine; Wissing, Marie Louise; Salö, Sofia; Englund, Anne Lis Mikkelsen; Dalgaard, Louise Torp

    2014-01-01

    Polycystic ovary syndrome (PCOS) is the most common, though heterogeneous, endocrine aberration in women of reproductive age, with high prevalence and socioeconomic costs. The syndrome is characterized by polycystic ovaries, chronic anovulation and hyperandrogenism, as well as being associated with infertility, insulin resistance, chronic low-grade inflammation and an increased life time risk of type 2 diabetes. MicroRNAs (miRNAs) are small, non-coding RNAs that are able to regulate gene expression at the post-transcriptional level. Altered miRNA levels have been associated with diabetes, insulin resistance, inflammation and various cancers. Studies have shown that circulating miRNAs are present in whole blood, serum, plasma and the follicular fluid of PCOS patients and that they might serve as potential biomarkers and a new approach for the diagnosis of PCOS. In this review, recent work on miRNAs with respect to PCOS will be summarized. Our understanding of miRNAs, particularly in relation to PCOS, is currently at a very early stage, and additional studies will yield important insight into the molecular mechanisms behind this complex and heterogenic syndrome. PMID:25158044

  2. Treatment strategies for infertile women with polycystic ovary syndrome.

    PubMed

    Vitek, Wendy; Hoeger, Kathleen; Legro, Richard S

    2016-08-01

    Polycystic ovary syndrome (PCOS) is a common reproductive disorder that can be diagnosed when two of the following three criteria are present: menstrual irregularity, hyperandrogenism and polycystic ovaries. Factors such as the individual's body weight influence the severity of the phenotype and risk of metabolic comorbidities. While anovulatory infertility is a common issue among lean and obese reproductive-aged women with PCOS, obesity is associated with resistance to oral ovulation induction agents, lower pregnancy rates and a higher risk of pregnancy complications. Lifestyle modification is recommended as first line therapy among obese women with PCOS in order to optimize their outcomes. Among lean and obese women with PCOS, ovulation induction can be achieved with aromatase inhibitors, selective estrogen receptor modulators, insulin sensitizing agents, gonadotropins and ovarian drilling with varying rates of ovulation, live birth and multiple gestations. Assisted reproductive technologies are reserved for women who do not conceive despite restoration of ovulation or couples with additional factors contributing to their infertility. This review will outline treatment strategies for achieving a healthy pregnancy among lean and obese women with PCOS and infertility. PMID:26765152

  3. Hyperandrogenemia in Polycystic Ovary Syndrome: Exploration of the Role of Free Testosterone and Androstenedione in Metabolic Phenotype

    PubMed Central

    Lerchbaum, Elisabeth; Schwetz, Verena; Rabe, Thomas; Giuliani, Albrecht; Obermayer-Pietsch, Barbara

    2014-01-01

    Objective To evaluate the association between androstenedione, testosterone, and free testosterone and metabolic disturbances in polycystic ovary syndrome. Methods We analyzed the association between androstenedione, testosterone, and free testosterone and metabolic parameters in a cross-sectional study including 706 polycystic ovary syndrome and 140 BMI-matched healthy women. Polycystic ovary syndrome women were categorized into 4 groups: normal androstenedione and normal free testosterone (NA/NFT), elevated androstenedione and normal free testosterone (HA/NFT), normal androstenedione and elevated free testosterone (NA/HFT), elevated androstenedione and free testosterone (HA/HFT). Results Polycystic ovary syndrome women with elevated free testosterone levels (HA/HFT and NA/HFT) have an adverse metabolic profile including 2 h glucose, HbA1c, fasting and 2 h insulin, area under the insulin response curve, insulin resistance, insulin sensitivity index (Matsuda), triglycerides, total and high density lipoprotein cholesterol levels compared to NA/NFT (p<0.05 for all age- and BMI-adjusted analyses). In binary logistic regression analysis adjusted for age and BMI, odds ratio for insulin resistance was 2.78 (1.34–5.75, p = 0.006) for polycystic ovary syndrome women with HA/HFT compared to NA/NFT. We found no significantly increased risk of metabolic disorders in polycystic ovary syndrome women with HA/NFT. In multiple linear regression analyses (age- and BMI-adjusted), we found a significant negative association between androstenedione/free testosterone-ratio and area under the insulin response curve, insulin resistance, and total cholesterol/high density lipoprotein cholesterol-ratio and a positive association with Matsuda-index, and high density lipoprotein cholesterol (p<0.05 for all). Conclusions Polycystic ovary syndrome women with elevated free testosterone levels but not with isolated androstenedione elevation have an adverse metabolic phenotype. Further, a

  4. Mammalian Endogenous Retroviruses.

    PubMed

    Mager, Dixie L; Stoye, Jonathan P

    2015-02-01

    Over 40% of mammalian genomes comprise the products of reverse transcription. Among such retrotransposed sequences are those characterized by the presence of long terminal repeats (LTRs), including the endogenous retroviruses (ERVs), which are inherited genetic elements closely resembling the proviruses formed following exogenous retrovirus infection. Sequences derived from ERVs make up at least 8 to 10% of the human and mouse genomes and range from ancient sequences that predate mammalian divergence to elements that are currently still active. In this chapter we describe the discovery, classification and origins of ERVs in mammals and consider cellular mechanisms that have evolved to control their expression. We also discuss the negative effects of ERVs as agents of genetic disease and cancer and review examples of ERV protein domestication to serve host functions, as in placental development. Finally, we address growing evidence that the gene regulatory potential of ERV LTRs has been exploited multiple times during evolution to regulate genes and gene networks. Thus, although recently endogenized retroviral elements are often pathogenic, those that survive the forces of negative selection become neutral components of the host genome or can be harnessed to serve beneficial roles. PMID:26104559

  5. Effect of ovary induction on bread wheat anther culture: ovary genotype and developmental stage, and candidate gene association.

    PubMed

    Castillo, Ana M; Sánchez-Díaz, Rosa A; Vallés, María P

    2015-01-01

    Ovary pre-conditioned medium and ovary co-culture increased the efficiency of green doubled haploid plant production in bread wheat anther culture. The positive effect of this medium led to a 6- and 11-fold increase in the numbers of embryos and green plants, respectively, having a greater effect on a medium-low responding cultivar. Ovary genotype and developmental stage significantly affected microspore embryogenesis. By the use of Caramba ovaries it was possible to reach a 2-fold increase in the number of embryos and green plants, and to decrease the rate of albinism. Mature ovaries from flowers containing microspores at a late binucleate stage raised the number of embryos and green plants by 25-46% as compared to immature ovaries (excised from flowers with microspores at a mid-late uninucleate stage). The highest numbers of embryos and green plants were produced when using mature Caramba ovaries. Ovaries from Galeón, Tigre, and Kilopondio cultivars successfully induced microspore embryogenesis at the same rate as Caramba ovaries. Moreover, Tigre ovaries raised the percentage of spontaneous chromosome doubling up to 71%. Attempts were made to identify molecular mechanisms associated to the inductive effect of the ovaries on microspore embryogenesis. The genes TAA1b, FLA26, and WALI6 associated to wheat microspore embryogenesis, the CGL1 gene involved in glycan biosynthesis or degradation, and the FER gene involved in the ovary signaling process were expressed and/or induced at different rates during ovary culture. The expression pattern of FLA26 and FER could be related to the differences between genotypes and developmental stages in the inductive effect of the ovary. Our results open opportunities for new approaches to increase bread wheat doubled haploid production by anther culture, and to identify the functional components of the ovary inductive effect on microspore embryogenesis. PMID:26150821

  6. MAMMALIAN APOPTOSIS IN WHOLE NEONATAL OVARIES, EMBRYOS AND FETAL LIMBS USING CONFOCAL MICROSCOPY

    EPA Science Inventory

    The emergence of confocal laser scanning microscopy (CLSM) as a technique capable of optically generating serial sections of whole-mount tissue and then reassembling the computer-stored images as a virtual 3-dimensional structure offers a viable alternative to traditional section...

  7. Development of a technique for efficient gene transfer to antral follicular cells in the mouse ovary.

    PubMed

    Sato, Masahiro; Akasaka, Eri; Saitoh, Issei; Ohtsuka, Masato; Watanabe, Satoshi

    2012-06-01

    Ovarian follicle development is a complex process mediated by interactions between oocytes and surrounding follicular cells. In an ovary, oocytes are ultimately released from Graafian follicles, which develop from antral follicles localized near the surface of an ovary. To examine the molecular interaction between these 2 cell types, direct gene transfer to follicular cells as well as oocytes appears to be a promising approach, but few studies have applied this technique. The aim of the present study was to develop a technique for gene transfer to antral follicle cells based on their accessibility near the surface of an ovary. B6C3F1 (a hybrid between C57BL6/N and C3H/HeN) female mice aged 4 or 8 w were anesthesized and their ovaries were exposed. About 100 nl of a solution containing reporter plasmid DNA (0.5 µg/μl) and 0.1% trypan blue was injected into a follicle using a glass micropipette attached to the mouthpiece. A total of 6 follicles were injected per ovary. After injection, the ovary was immediately subjected to in vivo electroporation (EP) using an electroporator with 8 square electric pulses of 50 ms and 50 V. After 24 h, the treated ovaries were excised to examine the expression of reporter constructs by histochemistry. All the injected follicles expressed reporter genes to different extents. Inspection of cryostat sections of ovaries injected with the lacZ expression plasmid demonstrated that 50-100% of follicular cells within a follicle were successfully transfected. However, there were no oocytes within the antral follicles that were negative for such staining (15 follicles tested). Similar results were obtained when the enhanced green fluorescent protein expression plasmid was introduced. The present method based on in vivo EP was found to be very effective for transfection of follicular cells. This approach might be useful to explore the roles of genes related to oogenesis/folliculogenesis, and for reproductive manipulation targeted to antral

  8. Mammalian phospholipase C.

    PubMed

    Kadamur, Ganesh; Ross, Elliott M

    2013-01-01

    Phospholipase C (PLC) converts phosphatidylinositol 4,5-bisphosphate (PIP(2)) to inositol 1,4,5-trisphosphate (IP(3)) and diacylglycerol (DAG). DAG and IP(3) each control diverse cellular processes and are also substrates for synthesis of other important signaling molecules. PLC is thus central to many important interlocking regulatory networks. Mammals express six families of PLCs, each with both unique and overlapping controls over expression and subcellular distribution. Each PLC also responds acutely to its own spectrum of activators that includes heterotrimeric G protein subunits, protein tyrosine kinases, small G proteins, Ca(2+), and phospholipids. Mammalian PLCs are autoinhibited by a region in the catalytic TIM barrel domain that is the target of much of their acute regulation. In combination, the PLCs act as a signaling nexus that integrates numerous signaling inputs, critically governs PIP(2) levels, and regulates production of important second messengers to determine cell behavior over the millisecond to hour timescale. PMID:23140367

  9. The mammalian blastocyst.

    PubMed

    Frankenberg, Stephen R; de Barros, Flavia R O; Rossant, Janet; Renfree, Marilyn B

    2016-01-01

    The blastocyst is a mammalian invention that carries the embryo from cleavage to gastrulation. For such a simple structure, it exhibits remarkable diversity in its mode of formation, morphology, longevity, and intimacy with the uterine endometrium. This review explores this diversity in the light of the evolution of viviparity, comparing the three main groups of mammals: monotremes, marsupials, and eutherians. The principal drivers in blastocyst evolution were loss of yolk coupled with evolution of the placenta. An important outcome of blastocyst development is differentiation of two extraembryonic lineages (trophoblast and hypoblast) that contribute to the placenta. While in many species trophoblast segregation is often coupled with blastocyst formation, in marsupials and at least some Afrotherians, these events do not coincide. Thus, many questions regarding the conservation of molecular mechanisms controlling these events are of great interest but currently unresolved. For further resources related to this article, please visit the WIREs website. PMID:26799266

  10. The endothelial nitric oxide synthase/nitric oxide system is involved in the defective quality of bovine oocytes from low mid-antral follicle count ovaries.

    PubMed

    Tessaro, I; Luciano, A M; Franciosi, F; Lodde, V; Corbani, D; Modina, S C

    2011-08-01

    In a previous survey concerning cows of reproductive age, we demonstrated that oocytes isolated from ovaries with <10 medium antral follicles of 2 to 6 mm in diameter (low ovaries; Lo) show less developmental competence than oocytes collected from ovaries with >10 medium antral follicles (high ovaries; Hi). The aim of the present study was to evaluate whether a defective endothelial nitric oxide synthase/nitric oxide (eNOS/NO) system and vasculature in healthy medium antral follicles is likely to reduce oocyte competence from Lo ovaries. Thus, experiments were conducted to 1) immunolocalize eNOS protein during folliculogenesis; 2) quantify eNOS protein/vasculature in the follicle wall; and 3) verify if NO donor, S-nitroso acetyl penicillamine (SNAP) administration during in vitro maturation affects developmental competence of oocytes isolated from Lo ovaries. Endothelial nitric oxide synthase protein was detected in granulosa and theca cells, as well as in blood vessels from primordial to antral follicles. Quantitative analysis indicated that in medium antral follicles from Lo ovaries, eNOS protein expression and vasculature were reduced (P < 0.05). The addition of SNAP improved blastocyst and hatching rates of oocytes from Lo ovaries, promoting a percentage similar to oocytes from Hi ovaries, and reduced the percentage of apoptotic nuclei in in vitro-produced blastocysts (P < 0.05). Results from our study suggest that in bovine ovaries with small mid antral follicle number, a defective eNOS/NO system is related to a reduced follicle vasculature and may affect oocyte quality, thus inducing a premature decline of fertility. PMID:21421835

  11. Criteria, prevalence, and phenotypes of polycystic ovary syndrome.

    PubMed

    Lizneva, Daria; Suturina, Larisa; Walker, Walidah; Brakta, Soumia; Gavrilova-Jordan, Larisa; Azziz, Ricardo

    2016-07-01

    Polycystic ovary syndrome (PCOS) is a highly prevalent disorder effecting reproductive-aged women worldwide. This article addresses the evolution of the criteria used to diagnosis PCOS; reviews recent advances in the phenotypic approach, specifically in the context of the extended Rotterdam criteria; discusses limitations of the current criteria used to diagnosis, particularly when studying adolescents and women in the peri- and postmenopause; and describes significant strides made in understanding the epidemiology of PCOS. This review recognizes that although there is a high prevalence of PCOS, there is increased variability when using Rotterdam 2003 criteria, owing to limitations in population sampling and approaches used to define PCOS phenotypes. Last, we discuss the distribution of PCOS phenotypes, their morbidity, and the role that referral bias plays in the epidemiology of this syndrome. PMID:27233760

  12. Mood disorders and quality of life in polycystic ovary syndrome.

    PubMed

    Podfigurna-Stopa, Agnieszka; Luisi, Stefano; Regini, Cristina; Katulski, Krzysztof; Centini, Gabriele; Meczekalski, Blazej; Petraglia, Felice

    2015-06-01

    Polycystic ovary syndrome (PCOS) affects 5-10% of the population of women. The exact etiology of PCOS remains unclear, but it is believed to result from complex interactions between genetic, behavioral and environmental factors. The spectrum of its symptoms such as hirsutism, skin problems, obesity and finally infertility has a huge negative impact on the individuals' psychological and interpersonal functioning. PCOS symptoms can lead to significant deterioration in quality of life and be highly stressful negatively affecting psychological well-being and sexuality. Fear symptoms like palpitation, being out of breath and tension might be caused by many somatic diseases. Moreover, detection and continuous thinking about illness can lead to significant negative impact on individual functioning in society. PCOS may be a factor potentially favoring the occurrence of mood disorders and depression. Biological, social and psychological consequences of PCOS among women of reproductive age are opening a new perspective on management of women's health in these patients. PMID:26204044

  13. Polycystic ovary syndrome: update on diagnosis and treatment.

    PubMed

    Setji, Tracy L; Brown, Ann J

    2014-10-01

    Polycystic ovary syndrome is now a well-recognized condition affecting 6%-25% of reproductive-aged women, depending on the definition. Over the past 3 decades, research has launched it from relative medical obscurity to a condition increasingly recognized as common in internal medicine practices. It affects multiple systems, and requires a comprehensive perspective on health care for effective treatment. Metabolic derangements and associated complications include insulin resistance and diabetes, hyperlipidemia, hypertension, fatty liver, metabolic syndrome, and sleep apnea. Reproductive complications include oligo-/amenorrhea, sub-fertility, endometrial hyperplasia, and cancer. Associated psychosocial concerns include depression and disordered eating. Additionally, cosmetic issues include hirsutism, androgenic alopecia, and acne. This review organizes this multi-system approach around the mnemonic "MY PCOS" and discusses evaluation and treatment options for the reproductive, cosmetic, and metabolic complications of this condition. PMID:24859638

  14. Nonhuman primate models of polycystic ovary syndrome

    PubMed Central

    Abbott, David H; Nicol, Lindsey E; Levine, Jon E; Xu, Ning; Goodarzi, Mark O; Dumesic, Daniel A

    2013-01-01

    With close genomic and phenotypic similarity to humans, nonhuman primate models provide comprehensive epigenetic mimics of polycystic ovary syndrome (PCOS), suggesting early life targeting for prevention. Fetal exposure to testosterone (T), of all nonhuman primate emulations, provides the closest PCOS-like phenotypes, with early-to-mid gestation T-exposed female rhesus monkeys exhibiting adult reproductive, endocrinological and metabolic dysfunctional traits that are co-pathologies of PCOS. Late gestational T exposure, while inducing adult ovarian hyperandrogenism and menstrual abnormalities, has less dysfunctional metabolic accompaniment. Fetal exposures to dihydrotestosterone (DHT) or diethylstilbestrol (DES) suggest androgenic and estrogenic aspects of fetal programming. Neonatal exposure to T produces no PCOS-like outcome, while continuous T treatment of juvenile females causes precocious weight gain and early menarche (high T), or high LH and weight gain (moderate T). Acute T exposure of adult females generates polyfollicular ovaries, while chronic T exposure induces subtle menstrual irregularities without metabolic dysfunction. PMID:23370180

  15. The Effects of Phthalates on the Ovary

    PubMed Central

    Hannon, Patrick R.; Flaws, Jodi A.

    2015-01-01

    Phthalates are commonly used as plasticizers in the manufacturing of flexible polyvinyl chloride products. Large production volumes of phthalates and their widespread use in common consumer, medical, building, and personal care products lead to ubiquitous human exposure via oral ingestion, inhalation, and dermal contact. Recently, several phthalates have been classified as reproductive toxicants and endocrine-disrupting chemicals based on their ability to interfere with normal reproductive function and hormone signaling. Therefore, exposure to phthalates represents a public health concern. Currently, the effects of phthalates on male reproduction are better understood than the effects on female reproduction. This is of concern because women are often exposed to higher levels of phthalates than men through their extensive use of personal care and cosmetic products. In the female, a primary regulator of reproductive and endocrine function is the ovary. Specifically, the ovary is responsible for folliculogenesis, the proper maturation of gametes for fertilization, and steroidogenesis, and the synthesis of necessary sex steroid hormones. Any defect in the regulation of these processes can cause complications for reproductive and non-reproductive health. For instance, phthalate-induced defects in folliculogenesis and steroidogenesis can cause infertility, premature ovarian failure, and non-reproductive disorders. Presently, there is a paucity of knowledge on the effects of phthalates on normal ovarian function; however, recent work has established the ovary as a target of phthalate toxicity. This review summarizes what is currently known about the effects of phthalates on the ovary and the mechanisms by which phthalates exert ovarian toxicity, with a particular focus on the effects on folliculogenesis and steroidogenesis. Further, this review outlines future directions, including the necessity of examining the effects of phthalates at doses that mimic human exposure

  16. The effects of phthalates on the ovary.

    PubMed

    Hannon, Patrick R; Flaws, Jodi A

    2015-01-01

    Phthalates are commonly used as plasticizers in the manufacturing of flexible polyvinyl chloride products. Large production volumes of phthalates and their widespread use in common consumer, medical, building, and personal care products lead to ubiquitous human exposure via oral ingestion, inhalation, and dermal contact. Recently, several phthalates have been classified as reproductive toxicants and endocrine-disrupting chemicals based on their ability to interfere with normal reproductive function and hormone signaling. Therefore, exposure to phthalates represents a public health concern. Currently, the effects of phthalates on male reproduction are better understood than the effects on female reproduction. This is of concern because women are often exposed to higher levels of phthalates than men through their extensive use of personal care and cosmetic products. In the female, a primary regulator of reproductive and endocrine function is the ovary. Specifically, the ovary is responsible for folliculogenesis, the proper maturation of gametes for fertilization, and steroidogenesis, and the synthesis of necessary sex steroid hormones. Any defect in the regulation of these processes can cause complications for reproductive and non-reproductive health. For instance, phthalate-induced defects in folliculogenesis and steroidogenesis can cause infertility, premature ovarian failure, and non-reproductive disorders. Presently, there is a paucity of knowledge on the effects of phthalates on normal ovarian function; however, recent work has established the ovary as a target of phthalate toxicity. This review summarizes what is currently known about the effects of phthalates on the ovary and the mechanisms by which phthalates exert ovarian toxicity, with a particular focus on the effects on folliculogenesis and steroidogenesis. Further, this review outlines future directions, including the necessity of examining the effects of phthalates at doses that mimic human exposure

  17. Queen pheromone regulates programmed cell death in the honey bee worker ovary.

    PubMed

    Ronai, I; Oldroyd, B P; Vergoz, V

    2016-10-01

    In social insect colonies the presence of a queen, secreting her pheromones, is a key environmental cue for regulating the reproductive state of workers. However, until recently the proximate molecular mechanisms underlying facultative worker sterility were unidentified. Studies into worker oogenesis in the honey bee (Apis mellifera) have indicated that programmed cell death is central to the regulation of oogenesis. Here we investigate how queen pheromone, age of the worker and ovary state affect both programmed cell death and cell number in worker ovaries. We describe a novel method to simultaneously measure programmed cell death (caspase activity) and live cell number (estimated from the amount of adenosine triphosphate) in an insect tissue. Workers exposed to queen pheromone have higher levels of caspase activity in the ovary than those not exposed. Our results suggest that queen pheromone triggers programmed cell death at the mid-oogenesis checkpoint causing the abortion of worker oocytes and reproductive inhibition of the worker caste. Nonetheless, high caspase activity is present in activated ovaries from workers not exposed to queen pheromone. This caspase activity is most likely to be from the nurse cells undergoing programmed cell death, in late oogenesis, for normal oocyte development. Our study shows that the social environment of an organism can influence programmed cell death within a tissue. PMID:27321063

  18. Ribosomal protein S6 kinase 1 signaling regulates mammalian lifespan

    PubMed Central

    Selman, Colin; Tullet, Jennifer M.A.; Wieser, Daniela; Irvine, Elaine; Lingard, Steven J.; Choudhury, Agharul I.; Claret, Marc; Al-Qassab, Hind; Carmignac, Danielle; Ramadani, Faruk; Woods, Angela; Robinson, Iain C.A.; Schuster, Eugene; Batterham, Rachel L.; Kozma, Sara C.; Thomas, George; Carling, David; Okkenhaug, Klaus; Thornton, Janet M.; Partridge, Linda; Gems, David; Withers, Dominic J.

    2016-01-01

    Caloric restriction (CR) protects against aging and disease but the mechanisms by which this affects mammalian lifespan are unclear. We show in mice that deletion of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway component ribosomal S6 protein kinase 1 (S6K1) led to increased lifespan and resistance to age-related pathologies such as bone, immune and motor dysfunction and loss of insulin sensitivity. Deletion of S6K1 induced gene expression patterns similar to those seen in CR or with pharmacological activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), a conserved regulator of the metabolic response to CR. Our results demonstrate that S6K1 influences healthy mammalian lifespan, and suggest therapeutic manipulation of S6K1 and AMPK might mimic CR and provide broad protection against diseases of aging. PMID:19797661

  19. Trace Elements in Ovaries: Measurement and Physiology.

    PubMed

    Ceko, Melanie J; O'Leary, Sean; Harris, Hugh H; Hummitzsch, Katja; Rodgers, Raymond J

    2016-04-01

    Traditionally, research in the field of trace element biology and human and animal health has largely depended on epidemiological methods to demonstrate involvement in biological processes. These studies were typically followed by trace element supplementation trials or attempts at identification of the biochemical pathways involved. With the discovery of biological molecules that contain the trace elements, such as matrix metalloproteinases containing zinc (Zn), cytochrome P450 enzymes containing iron (Fe), and selenoproteins containing selenium (Se), much of the current research focuses on these molecules, and, hence, only indirectly on trace elements themselves. This review focuses largely on two synchrotron-based x-ray techniques: X-ray absorption spectroscopy and x-ray fluorescence imaging that can be used to identify the in situ speciation and distribution of trace elements in tissues, using our recent studies of bovine ovaries, where the distribution of Fe, Se, Zn, and bromine were determined. It also discusses the value of other techniques, such as inductively coupled plasma mass spectrometry, used to garner information about the concentrations and elemental state of the trace elements. These applications to measure trace elemental distributions in bovine ovaries at high resolutions provide new insights into possible roles for trace elements in the ovary. PMID:26864198

  20. Autoimmunity to endometrium and ovary in endometriosis.

    PubMed Central

    Mathur, S; Peress, M R; Williamson, H O; Youmans, C D; Maney, S A; Garvin, A J; Rust, P F; Fudenberg, H H

    1982-01-01

    Antibody titres to whole ovary, theca cells, granulosa cells and endometrium were determined by passive haemagglutination and immunofluorescence assays in sera and in cervical and vaginal secretions from 13 patients with endometriosis. Antibody titres to endometrium (mean log2 +/- s.e.m., 7.08 +/- 0.80; P less than 0.0001), ovary (3.58 +/- 0.87; P = 0.0092), theca cells (4.42 +/- 0.73; P less than 0.0001) and granulosa cells (3.33 +/- 0.63; P = 0.0024) were significantly higher in the patients' sera than in sera from 15 normal non-pregnant females. Antibody titres to granulosa cells were elevated (7.97 +/- 1.46; P = 0.0424) in their cervical secretions. Antibody titres to all tissues tested were similar in vaginal secretions of patients and controls. Immunofluorescent antibody assay of biopsied endometrial tissue and sera from the patients revealed the antibodies to be primarily IgG and IgA. The results suggest that autoantibodies to endometrium and ovary are present in patients with endometriosis. Images Fig. 1 Fig. 2 Fig. 3 PMID:6759000

  1. Lymphangioma of the ovary: etiology and management.

    PubMed

    Radhouane, Achour; Mayada, Saadaoui; Khaled, Neji

    2016-08-01

    Lymphangioma of the ovary is an extremely rare lesion. It was first described in 1908 [1] and there is only 19 cases reports in a 50-year literature survey [2]. Lymphangiomas are benign congenital malformations of lymphatic system. They are thought to happen due to obstruction of local lymph flow system and they can occur anywhere in the skin and the mucous membranes. Most common sites are the head and the neck and sometimes they can be found in the intestines, the pancreas and the mesentery. Lymphangioma of the ovary is a very rare tumor. Typically, lymphangiomas are slow-growing tumors that remain asymptomatic for a long time, with the tumor being identified incidentally during histopathological examination after excision. A 36-year-old women who consulted our department for infertility for 2 years. The systematic ultrasound examination reveals a right ovarian mass. The histologic analysis confirmed the diagnosis of cystic lymphangioma of the right ovary. She was planned for total laparoscopic tumorectomy with removal of all ovarian mass. The evolution was good for one year within Clinical and ultrasound monitoring. We report through this case report a review of the literature. PMID:27401696

  2. Melamine Induces Oxidative Stress in Mouse Ovary

    PubMed Central

    Dai, Xiao-Xin; Duan, Xing; Cui, Xiang-Shun; Kim, Nam-Hyung; Xiong, Bo; Sun, Shao-Chen

    2015-01-01

    Melamine is a nitrogen heterocyclic triazine compound which is widely used as an industrial chemical. Although melamine is not considered to be acutely toxic with a high LD50 in animals, food contaminated with melamine expose risks to the human health. Melamine has been reported to be responsible for the renal impairment in mammals, its toxicity on the reproductive system, however, has not been adequately assessed. In the present study, we examined the effect of melamine on the follicle development and ovary formation. The data showed that melamine increased reactive oxygen species (ROS) levels, and induced granulosa cell apoptosis as well as follicle atresia. To further analyze the mechanism by which melamine induces oxidative stress, the expression and activities of two key antioxidant enzymes superoxide dismutase (SOD) and glutathi-one peroxidase (GPX) were analyzed, and the concentration of malondialdehyde (MDA) were compared between control and melamine-treated ovaries. The result revealed that melamine changed the expression and activities of SOD and GPX in the melamine-treated mice. Therefore, we demonstrate that melamine causes damage to the ovaries via oxidative stress pathway. PMID:26545251

  3. Polycystic ovary syndrome: symptomatology, pathophysiology, and epidemiology.

    PubMed

    Guzick, D

    1998-12-01

    Women with polycystic ovary syndrome seek health care for 3 major reasons: infertility, menstrual irregularity, and androgen excess. The infertility is associated with anovulation. The menstrual irregularity is typically chronic, beginning with menarche. Although amenorrhea may sometimes occur, the more common presentation is irregular bleeding characteristic of anovulation. Androgen excess may be manifested by varying degrees of hirsutism. Patients may also report acne. The rapid development of virilizing signs, such as deepening of the voice, increased muscle mass, and temporal balding, should prompt a search for a tumor and lead one away from a diagnosis of polycystic ovary syndrome. Typically treatment is directed at alleviating the symptoms: ovulation induction for infertility, oral contraceptives or a progestin for menstrual irregularity, and oral contraceptives or spironolactone for hirsutism. On the basis of recent epidemiologic data suggestive of increased cardiovascular risk among women with polycystic ovary syndrome, such treatment might be complemented by a long-term approach that addresses the underlying pathophysiology of insulin resistance. PMID:9855614

  4. Transient transfection of mammalian cells using a violet diode laser

    NASA Astrophysics Data System (ADS)

    Torres-Mapa, Maria Leilani; Angus, Liselotte; Ploschner, Martin; Dholakia, Kishan; Gunn-Moore, Frank J.

    2010-07-01

    We demonstrate the first use of the violet diode laser for transient mammalian cell transfection. In contrast to previous studies, which showed the generation of stable cell lines over a few weeks, we develop a methodology to transiently transfect cells with an efficiency of up to ~40%. Chinese hamster ovary (CHO-K1) and human embryonic kidney (HEK293) cells are exposed to a tightly focused 405-nm laser in the presence of plasmid DNA encoding for a mitochondrial targeted red fluorescent protein. We report transfection efficiencies as a function of laser power and exposure time for our system. We also show, for the first time, that a continuous wave laser source can be successfully applied to selective gene silencing experiments using small interfering RNA. This work is a major step towards an inexpensive and portable phototransfection system.

  5. Trehalose Transporter from African Chironomid Larvae Improves Desiccation Tolerance of Chinese Hamster Ovary Cells

    PubMed Central

    Chakraborty, Nilay; Menze, Michael A.; Elmoazzen, Heidi; Vu, Halong; Yarmush, Martin L.; Hand, Steven C.; Toner, Mehmet

    2011-01-01

    Dry preservation has been explored as an energy-efficient alternative to cryopreservation, but the high sensitivity of mammalian cells to desiccation stress has been one of the major hurdles in storing cells in the desiccated state. An important strategy to reduce desiccation sensitivity involves use of the disaccharide trehalose. Trehalose is known to improve desiccation tolerance in mammalian cells when present on both sides of the cell membrane. Because trehalose is membrane impermeant the development of desiccation strategies involving this promising sugar is hindered. We explored the potential of using a high-capacity trehalose transporter (TRET1) from the African chironomid P. vanderplanki [21] to introduce trehalose into the cytoplasm of mammalian cells and thereby increase desiccation tolerance. When Chinese Hamster Ovary cells (CHO) were stably transfected with TRET1 (CHO-TRET1 cells) and incubated with 0.4 M trehalose for 4 h at 37 °C, a seven-fold increase in trehalose uptake was observed compared to the wild-type CHO cells. Following trehalose loading, desiccation tolerance was investigated by evaporative drying of cells at 14 % relative humidity. After desiccation to 2.60 g of water per gram dry weight, a 170 % increase in viability and a 400 % increase in growth (after 7 days) was observed for CHO-TRET1 relative to control CHO cells. Our results demonstrate the beneficial effect of intracellular trehalose for imparting tolerance to partial desiccation. PMID:22155480

  6. Involvement of nitric oxide in inflammation of ovaries in gilts.

    PubMed

    Jana, Barbara; Andronowska, Aneta; Kucharski, Jan

    2002-03-01

    NADPH-diaphorase (NADPH-d) and an inducible type of nitric oxide synthase (iNOS) were demonstrated in porcine ovaries after unilateral infusion of bacteria into the hilus of an ovary. In group I one ml of saline was infused into the hilus of each ovary from the 15th day to the 19th day of the estrous cycle. In group II one ml of bacterial suspension (10(9) colony forming units of Escherichia coli, Staphylococcus aureus and Corynebacterium pyogenes, in a proportion 1:1:1, respectively) in saline was infused into the hilus of one ovary on days corresponding to those of the control group (gr. I), whereas saline was infused into the contralateral ovary. The ovaries were collected on the 7th day of the next estrous cycle. In the bacteria-treated ovary, the activity of NADPH-d was higher in the endothelium of blood vessels, corpora lutea and follicular walls in comparison to that observed in the respective structures of the contralateral ovary. The highest activity of NADPH-d was found in the vascular endothelium in the bacteria-infused ovary. Vascular smooth muscle cells found in both ovaries of the bacteria-treated gilts were more intensely stained for NADPH-d than those in control animals. After bacteria administration, the intensity of NADPH-d reaction in all the structures of both ovaries in group II was higher than in control group. The strongest immunostaining for iNOS was observed in all structures of the bacteria-infused ovary. In the contralateral ovary, iNOS-immunoreactivity was weaker but still stronger than that in control group. The present results revealed that infusions of bacteria into the hilus of one ovary enhanced the activity of NADPH-d and immunoreactivity for iNOS in both porcine ovaries. However, the activity of both enzymes was higher in the bacteria-infused ovary than in the contralateral one. These data suggest that locally synthesized NO can mediate an inflammatory effect of bacteria in the porcine ovaries. PMID:14666163

  7. Radioimmunotherapy of Cryptococcus neoformans spares bystander mammalian cells

    PubMed Central

    Bryan, Ruth A; Jiang, Zewei; Morgenstern, Alfred; Bruchertseifer, Frank; Casadevall, Arturo; Dadachova, Ekaterina

    2013-01-01

    Aim Previously, we showed that radioimmunotherapy (RIT) for cryptococcal infections using radioactively labeled antibodies recognizing the cryptococcal capsule reduced fungal burden and prolonged survival of mice infected with Cryptococcus neoformans. Here, we investigate the effects of RIT on bystander mammalian cells. Materials & methods Heat-killed C. neoformans bound to anticapsular antibodies, unlabeled or labeled with the β-emitter rhenium-188 (16.9-h half-life) or the α-emitter bismuth-213 (46-min half-life), was incubated with macrophage-like J774.16 cells or epithelial-like Chinese hamster ovary cells. Lactate dehydrogenase activity, crystal violet uptake, reduction of tetrazolium dye (2,3)-bis-(2-methoxy-4-nitro-5-sulfenyl)-(2H)-terazolium-5-carboxanilide and nitric oxide production were measured. Results The J774.16 and Chinese hamster ovary cells maintained membrane integrity, viability and metabolic activity following exposure to radiolabeled C. neoformans. Conclusion RIT of C. neoformans is a selective therapy with minimal effects on host cells and these results are consistent with observations that RIT-treated mice with cryptococcal infection lacked RIT-related pathological changes in lungs and brain tissues. PMID:24020737

  8. Growth and development of the ovary and small follicle pool from mid fetal life to pre-puberty in the African elephant (Loxodonta africana)

    PubMed Central

    2012-01-01

    Background Follicle numbers and developing ovarian morphology, particularly with reference to the presence of interstitial tissue, are intimately linked within the ovary of the African elephant during the period spanning mid-gestation to puberty. These have not been previously quantified in any studies. The collection of 7 sets of elephant fetal ovaries between 11.2 and 20.2 months of gestation, and 29 pairs of prepubertal calf ovaries between 2 months and 9 years of age during routine management off-takes of complete family groups in private conservancies in Zimbabwe provided an opportunity for a detailed study of this period. Results The changing morphology of the ovary is described as the presumptive cortex and medulla components of the fetal ovary settled into their adult form. Interstitial tissue dominated the ovary in late fetal life and these cells stained strongly for 3β–hydroxysteroid dehydrogenase. This staining continued postnatally through to 4.5 years of age suggesting continued secretion of progestagens by the ovary during this period. The considerable growth of antral follicles peaked at 28% of ovarian volume at around 16.7 months of fetal age. The numbers of small follicles (primordial, early primary and true primary), counted in the cortex using stereological protocols, revealed fewer small follicles in the ovaries of animals aged 0 to 4.5 years of age than during either late fetal life or prepubertal life. Conclusions The small follicle populations of the late-fetal and prepubertal ovaries of the African elephant were described along with the changing morphology of these organs. The changes noted represent a series of events that have been recorded only in the elephant and the giraffe species to date. The expansion of the interstitial tissue of the fetal ovary and its continued presence in early post natal life may well contribute to the control of follicle development in these early years. Further research is required to determine

  9. Evidence-Based Management of Infertility in Women With Polycystic Ovary Syndrome.

    PubMed

    Bergh, Catherine M; Moore, Monica; Gundell, Carolyn

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a polygenic disorder with a variable phenotype that commonly affects women of reproductive age. It can significantly affect a woman's ability to conceive and her quality of life. Effective treatment includes a multidisciplinary team approach that addresses the physiological and psychosocial manifestations of the disorder. Nurses have an important role in promoting early detection, education, and identification of services and resources to improve a woman's fertility and lifelong health. PMID:26815805

  10. [Telomere Recombination in Normal Mammalian Cells].

    PubMed

    Zhdanova, N S; Rubtsov, N B

    2016-01-01

    Two mechanisms of telomere length maintenance are known to date. The first includes the use of a special enzymatic telomerase complex to solve the problems that arise during the replication of linear DNA in a normal diploid and part of tumor cells. Alternative lengthening of telomeres (ALT), which is based on the homologous recombination of telomere DNA, represents the second mechanism. Until recently, ALT was assumed to be expressed only in 15-20% of tumors lacking active telomerase and, together with telomerase reactivation represented one of two possibilities to overcome the replicative senescence observed in somatic mammalian cells due to aging or during cell culturing in vitro. Previously described sporadic cases of combinations of the two mechanisms of telomere length maintenance in several cell lines in vitro were attributed to the experimental design rather than to a real biological phenomenon, since active cellular division without active telomerase was considered to be the "gold standard" of ALT. The present review describes the morphological and functional reorganizations of mammalian telomeres observed with ALT activation, as well as recently observed,and well-documented cases of combinations between ALT-like and telomerase-dependent mechanisms in mammalian cells. The possible role of telomere recombination in telomerase-dependent cells is discussed. PMID:27183789

  11. Mammalian Wax Biosynthesis

    PubMed Central

    Cheng, Jeffrey B.; Russell, David W.

    2009-01-01

    Wax monoesters are synthesized by the esterification of fatty alcohols and fatty acids. A mammalian enzyme that catalyzes this reaction has not been isolated. We used expression cloning to identify cDNAs encoding a wax synthase in the mouse preputial gland. The wax synthase gene is located on the X chromosome and encodes a member of the acyltransferase family of enzymes that synthesize neutral lipids. Expression of wax synthase in cultured cells led to the formation of wax monoesters from straight chain saturated, unsaturated, and polyunsaturated fatty alcohols and acids. Polyisoprenols also were incorporated into wax monoesters by the enzyme. The wax synthase had little or no ability to synthesize cholesteryl esters, diacylglycerols, or triacylglycerols, whereas other acyltransferases, including the acyl-CoA:monoacylglycerol acyltransferase 1 and 2 enzymes and the acyl-CoA:diacylglycerol acyltransferase 1 and 2 enzymes, exhibited modest wax monoester synthesis activities. Confocal light microscopy indicated that the wax synthase was localized in membranes of the endoplasmic reticulum. Wax synthase mRNA was abundant in tissues rich in sebaceous glands such as the preputial gland and eyelid and was present at lower levels in other tissues. Coexpression of cDNAs specifying fatty acyl-CoA reductase 1 and wax synthase led to the synthesis of wax monoesters. The data suggest that wax monoester synthesis in mammals involves a two step biosynthetic pathway catalyzed by fatty acyl-CoA reductase and wax synthase enzymes. PMID:15220349

  12. Structure of mammalian metallothionein

    SciTech Connect

    Kaegi, J.H.R.; Vasak, M.; Lerch, K.; Gilg, D.E.O.; Hunziker, P.; Bernhard, W.R.; Good, M.

    1984-03-01

    All mammalian metallothioneins characterized contain a single polypeptide chain of 61 amino acid residues, among them 20 cysteines providing the ligands for seven metal-binding sites. Native metallothioneins are usually heterogeneous in metal composition, with Zn, Cd, and Cu occurring in varying proportions. However, forms containing only a single metal species, i.e., Zn, Cd, Ni, Co, Hg, Pb, Bi, have now been prepared by in vitro reconstitution from the metal-free apoprotein. By spectroscopic analysis of such derivatives it was established that all cysteine residues participate in metal binding, that each metal ion is bound to four thiolate ligands, and that the symmetry of each complex is close to that of a tetrahedron. To satisfy the requirements of the overall Me/sub 7/(Cys/sup -/)/sub 20/ stoichiometry, the complexes must be combined to form metal-thiolate cluster structures. The actual spatial organization of the clusters and the polypeptide chain remains to be established. An attractive possibility is the arrangement of the tetrahedral metal-thiolates in adamantane-like structures surrounded by properly folded segments of the chain providing the ligands. /sup 1/H-NMR data and infrared absorption measurements are consistent with a tightly folded structure rich in ..beta..-type conformation. 79 references, 11 figures, 4 tables.

  13. Mammalian Sirtuins and Energy Metabolism

    PubMed Central

    Li, Xiaoling; Kazgan, Nevzat

    2011-01-01

    Sirtuins are highly conserved NAD+-dependent protein deacetylases and/or ADP-ribosyltransferases that can extend the lifespan of several lower model organisms including yeast, worms and flies. The seven mammalian sirtuins, SIRT1 to SIRT7, have emerged as key metabolic sensors that directly link environmental signals to mammalian metabolic homeostasis and stress response. Recent studies have shed light on the critical roles of sirtuins in mammalian energy metabolism in response to nutrient signals. This review focuses on the involvement of two nuclear sirtuins, SIRT1 and SIRT6, and three mitochondrial sirtuins, SIRT3, SIRT4, and SIRT5, in regulation of diverse metabolic processes. PMID:21614150

  14. Surgical transposition of the ovaries: Imaging findings in 14 patients

    SciTech Connect

    Kier, R.; Chambers, S.K. )

    1989-11-01

    Pelvic radiation therapy for cervical or vaginal cancer often leads to ovarian failure. To remove the ovaries from the radiation portal and preserve their function, they can be transposed to the lateral abdomen. Serial imaging studies in 14 patients who had undergone ovarian transposition (five bilateral, nine unilateral) were reviewed. Images obtained included 32 CT scans, 20 sonograms, and one MR image. Most transposed ovaries were located along the paracolic gutters near the iliac crests, creating an extrinsic mass effect on adjacent bowel. Detection of surgical clips on the ovary on CT scans allowed confident recognition of all 19 transposed ovaries. Cysts in the transposed ovaries, noted on most imaging studies, did not correlate with complications of pain or hormonal dysfunction. In one case, a large physiologic cyst in a transposed ovary distorted the cecum and was mistaken for a mucocele of the appendix. In another case, a large ovarian cyst was thought to be tumor recurrence or a lymphocele. These findings indicate that although the transposed ovaries can be recognized on CT scans by the surgical clips attached to the ovaries, the appearance of the ovary does not predict reliably the development of complications.

  15. Role of macrophage secretions on rat polycystic ovary: its effect on apoptosis.

    PubMed

    Figueroa, Florencia; Motta, Alicia; Acosta, Mariano; Mohamed, Fabian; Oliveros, Liliana; Forneris, Myriam

    2015-11-01

    Polycystic ovarian syndrome is the most common endocrine disorder among women of reproductive age. Little is known about its etiology, although the evidence suggests an intrinsic ovarian abnormality in which endocrine, metabolic, neural and immune factors would be involved. In this work, the effects of macrophage (MO) secretion on ovarian apoptosis in a polycystic ovary syndrome rat model (PCO rat) induced by estradiol valerate are studied. Spleen MO secretions were used to stimulate ovaries and ovarian interstitial and granulosa cells from both PCO and control rats. Ovarian hormones and prostaglandin E2 (PGE2) were measured by RIA; ovarian mRNA levels of Bax, Bcl2 and NFkB by RT-PCR; and ovarian inducible nitric oxide synthase (iNOS) by western blot. The number of apoptotic cells was evaluated by TUNEL. In the PCO ovary, the MO secretions from PCO rats increased the Bax and NFkB mRNA expressions and increased TUNEL staining in both granulosa and theca cells. In addition, the PCO MO secretions produced a decrease of nitric oxide release, iNOS protein level and PGE2 content in the PCO ovary, and it also induced an increase of androstenedione production by PCO interstitial cells, in comparison with control MO secretions. Considering these results and knowing that testosterone stimulates tumour necrosis factor-α production by PCO MO modifying ovarian response by increasing androstenedione, it is reasonable to suggest that the increase of androgens stimulated in ovarian cells by PCO MO secretions could in turn stimulate the cytokine production from MO, thus maintaining an apoptotic vicious cycle in the PCO ovary. PMID:26264225

  16. Polycystic ovary syndrome in patients on antiepileptic drugs

    PubMed Central

    Viswanathan, Lakshminarayanapuram G.; Satishchandra, Parthasarathy; Bhimani, Bipin C.; Reddy, Janardhan YC; Rama Murthy, Batchu S.; Subbakrishna, Doddaballapura K.; Sinha, Sanjib

    2016-01-01

    Objective: This study aims to discuss the prevalence of polycystic ovary (PCO) and Polycystic ovary syndrome (PCOS) in women with epilepsy (WWE) on valproate (VPA), carbamazepine (CBZ), or phenobarbitone (PB), drug naive WWE and women with bipolar affective disorder (BPAD) on VPA. Materials and Methods: This prospective study included 190 women aged 18–45 years, who had epilepsy or BPAD (on VPA), and consented for study. Patients were grouped as Group 1 (n = 40): WWE on VPA, Group 2 (n = 50): WWE on CBZ, Group 3 (n = 50): WWE on PB, Group 4 (n = 30): drug naïve WWE, and Group 5 (n = 20): women with BPAD on VPA. All women were interviewed for medical, menstrual, drug and treatment history, nature of epilepsy, and seizure control. Chi-square test and Fisher's exact test were done to compare results between the groups. Results: Fifty-two women (52/190; 27.4%) had menstrual disturbances, in which oligomenorrhea was the most common (55.8%). There was a significant difference in the occurrence of PCOS in patients on VPA versus normal population (P = 0.05) and patients on other antiepileptic drugs (AEDs) (P = 0.02). There was, however, no significant difference in the occurrence of PCO between patients on VPA and the untreated epileptic women. VPA group (Epilepsy + BPAD) had a significantly higher occurrence of obesity than other treatment groups (P = 0.043, OR = 2.11). Conclusions: The study observed significantly higher occurrence of PCO in patients on VPA compared to other AEDs and the normal population. The importance of proper clinical evaluation before initiating VPA is highlighted. PMID:27570385

  17. Mammalian DNA Repair. Final Report

    SciTech Connect

    2003-01-24

    The Gordon Research Conference (GRC) on Mammalian DNA Repair was held at Harbortown Resort, Ventura Beach, CA. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  18. Mammalian Interphase Cdks

    PubMed Central

    2012-01-01

    Cyclin-dependent kinases (Cdks) drive cell cycle progression in all eukaryotes. Yeasts have a single major Cdk that mediates distinct cell cycle transitions via association with different cyclins. The closest homolog in mammals, Cdk1, drives mitosis. Mammals have additional Cdks—Cdk2, Cdk4, and Cdk6—that represent the major Cdks activated during interphase (iCdks). A large body of evidence has accrued that suggests that activation of iCdks dictates progression though interphase. In apparent contradiction, deficiency in each individual iCdk, respectively, in knockout mice proved to be compatible with live birth and in some instances fertility. Moreover, murine embryos could be derived with Cdk1 as the only functional Cdk. Thus, none of the iCdks is strictly essential for mammalian cell cycle progression, raising the possibility that Cdk1 is the dominant regulator in interphase. However, an absence of iCdks has been accompanied by major shifts in cyclin association to Cdk1, suggesting gain in function. After considerable tweaking, a chemical genetic approach has recently been able to examine the impact of acute inhibition of Cdk2 activity without marked distortion of cyclin/Cdk complex formation. The results suggest that, when expressed at its normal levels, Cdk2 performs essential roles in driving human cells into S phase and maintaining genomic stability. These new findings appear to have restored order to the cell cycle field, bringing it full circle to the view that iCdks indeed play important roles. They also underscore the caveat in knockdown and knockout approaches that protein underexpression can significantly perturb a protein interaction network. We discuss the implications of the new synthesis for future cell cycle studies and anti–Cdk-based therapy of cancer and other diseases. PMID:23634250

  19. Isotope Labeling in Mammalian Cells

    PubMed Central

    Dutta, Arpana; Saxena, Krishna; Klein-Seetharaman, Judith

    2011-01-01

    Isotope labeling of proteins represents an important and often required tool for the application of nuclear magnetic resonance (NMR) spectroscopy to investigate the structure and dynamics of proteins. Mammalian expression systems have conventionally been considered to be too weak and inefficient for protein expression. However, recent advances have significantly improved the expression levels of these systems. Here, we provide an overview of some of the recent developments in expression strategies for mammalian expression systems in view of NMR investigations. PMID:22167668

  20. Stable Expression of the Motor Protein Prestin in Chinese Hamster Ovary Cells

    NASA Astrophysics Data System (ADS)

    Iida, Koji; Konno, Kazuaki; Oshima, Takeshi; Tsumoto, Kouhei; Ikeda, Katsuhisa; Kumagai, Izumi; Kobayashi, Toshimitsu; Wada, Hiroshi

    Mammalian hearing sensitivity relies on a mechanical amplification mechanism involving the outer hair cells (OHCs), which rapidly alter their longitudinal length in response to changes in their membrane potential. The molecular basis of this mechanism is thought to be a motor protein embedded in the lateral membrane of the OHCs. Recently, this motor protein was identified and termed prestin. Since then, prestin has been researched intensively to elucidate the behavior of the OHCs. However, little progress in the study of prestin at the molecular level has been made because no method of obtaining an adequate amount of prestin has been established. In this study, therefore, an attempt was made to construct a stable expression system of prestin using Chinese hamster ovary (CHO) cells. The expression of prestin in the transfected CHO cells and the activity of prestin on CHO cells were confirmed by immunofluorescence and whole-cell patch-clamp measurements, respectively.

  1. Studying the Functions of TGF-β Signaling in the Ovary.

    PubMed

    Yu, Chao; Zhou, Jian-Jie; Fan, Heng-Yu

    2016-01-01

    In mammals, ovulation is a multistep physiological process that includes preovulatory follicle growth, oocyte meiotic maturation, cumulus-oocyte complex (COC) expansion, follicle rupture, and luteinization. TGF-β signaling pathway has multiple functions in mammalian ovary, as its complexity in ovarian function has been demonstrated by mouse models with knockouts of TGF-β receptors and SMADs. We describe the protocol that we use to study functions of TGF-β signaling pathway in follicle development and ovulation. Because total knockout of TGF-β pathway components often causes embryonic lethality, which prevents further investigation of these genes in ovarian functions, people have generated ovarian cell type-specific knockout mouse strains for TGF-β signaling pathway genes. These mouse models are also described. PMID:26520133

  2. Body Mass Index and Gonadotropin Hormones (LH & FSH) Associate With Clinical Symptoms Among Women With Polycystic Ovary Syndrome

    PubMed Central

    Esmaeilzadeh, Seddigheh; Andarieh, Maryam Ghanbari; Ghadimi, Reza; Delavar, Mouloud Agajani

    2015-01-01

    To evaluate the relevance of body mass index (BMI), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and LH/FSH ratio with clinical symptoms in polycystic ovary syndrome (PCOS) women. Methods: We reviewed the medical records of all women visited in the PCOS Clinic of Babol (Iran) from 2008 to 2012. A retrospective cross-sectional study was conducted on 175 PCOS women; aged 18–38 years diagnosed based on the Rotterdam criteria. Among the PCOs women, the prevalence of oligomenorrhea, acne, and hirsutism were found to be 92.0%, 31.4%, and 78.9%, respectively. Positive finding of polycystic ovaries was observed in 89.1% of PCOS women with by using sonography. A total of 69.2% overweight/obesity patients had polycystic ovary morphology on ultrasound image. Compared with non- overweight/obesity, the adjusted OR of PCOS women for sonographic view of polycystic ovaries was 4.33 (95% CI, 1.42-13.15, p=0.001), Nevertheless, the adjusted odds ratio (OR) showed no significant associations between LH, FSH, and LH/FSH ratio with clinical symptoms in these women. The findings of this study indicated that the overweight/obese women with PCOS are at an increased risk for sonographic view of polycystic ovaries. Therefore, it is suggested that successful weight loss is the most effective method of restoring ovulation, menstruation that should be used as major advice in obese PCOS patients. PMID:25716399

  3. Intrafollicular levels of matrix metalloproteinases-2 and -9 in patients with polycystic ovaries are not associated with pregnancy rate during IVF cycle.

    PubMed

    Baka, Stavroula; Zourla, Konstantina; Malamitsi-Puchner, Ariadne; Makrakis, Evangelos; Kaparos, George; Demeridou, Stella; Moustakarias, Theodore; Tzanakaki, Despoina; Hassiakos, Dimitris; Kouskouni, Evangelia

    2009-01-01

    This study aimed to detect the levels of matrix metalloproteinases (MMP)-2 and -9, using enzyme-linked immunosorbent assays, in the follicular fluid of 35 patients with polycystic ovaries, compare them with the levels found in 35 normally ovulating women enrolled in their first in vitro fertilization (IVF) cycle and then correlate them with pregnancy rates in these two groups. Levels of MMP-9 were found significantly increased in women with polycystic ovaries when compared with the controls, while MMP-2 levels were higher in women with polycystic ovaries without reaching statistical significance. The two groups did not differ in age, in the number of embryos transferred or in pregnancy rates. In conclusion, the results indicated an increased gelatinolytic activity in patients with polycystic ovaries after ovarian stimulation for IVF treatment without detecting any association between levels of MMP-2 and 9 and IVF pregnancy rates. PMID:19368130

  4. Enhanced Production of Docosahexaenoic Acid in Mammalian Cells

    PubMed Central

    Zhu, Guiming; Jiang, Xudong; Ou, Qin; Zhang, Tao; Wang, Mingfu; Sun, Guozhi; Wang, Zhao; Sun, Jie; Ge, Tangdong

    2014-01-01

    Docosahexaenoic acid (DHA), one of the important polyunsaturated fatty acids (PUFA) with pharmaceutical and nutraceutical effects, may be obtained through diet or synthesized in vivo from dietary a-linolenic acid (ALA). However, the acumulation of DHA in human body or other mammals relies on the intake of high dose of DHA for a certain period of time, and the bioconversion of dietary ALA to DHA is very limited. Therefore the mammalian cells are not rich in DHA. Here, we report a new technology for increased prodution of DHA in mammalian cells. By using transient transfection method, Siganus canaliculatus Δ4 desaturase was heterologously expressed in chinese hamster ovary (CHO) cells, and simultaneously, mouse Δ6-desaturase and Δ5-desaturase were overexpressed. The results demonstrated that the overexpression of Δ6/Δ5-desaturases significantly enhanced the ability of transfected cells to convert the added ALA to docosapentaenoic acid (DPA) which in turn get converted into DHA directly and efficiently by the heterologously expressed Δ4 desaturase. This technology provides the basis for potential utility of these gene constructs in the creation of transgenic livestock for increased production of DHA/related products to meet the growing demand of this important PUFA. PMID:24788769

  5. Enhanced production of docosahexaenoic acid in mammalian cells.

    PubMed

    Zhu, Guiming; Jiang, Xudong; Ou, Qin; Zhang, Tao; Wang, Mingfu; Sun, Guozhi; Wang, Zhao; Sun, Jie; Ge, Tangdong

    2014-01-01

    Docosahexaenoic acid (DHA), one of the important polyunsaturated fatty acids (PUFA) with pharmaceutical and nutraceutical effects, may be obtained through diet or synthesized in vivo from dietary a-linolenic acid (ALA). However, the accumulation of DHA in human body or other mammals relies on the intake of high dose of DHA for a certain period of time, and the bioconversion of dietary ALA to DHA is very limited. Therefore the mammalian cells are not rich in DHA. Here, we report a new technology for increased production of DHA in mammalian cells. By using transient transfection method, Siganus canaliculatus Δ4 desaturase was heterologously expressed in chinese hamster ovary (CHO) cells, and simultaneously, mouse Δ6-desaturase and Δ5-desaturase were overexpressed. The results demonstrated that the overexpression of Δ6/Δ5-desaturases significantly enhanced the ability of transfected cells to convert the added ALA to docosapentaenoic acid (DPA) which in turn get converted into DHA directly and efficiently by the heterologously expressed Δ4 desaturase. This technology provides the basis for potential utility of these gene constructs in the creation of transgenic livestock for increased production of DHA/related products to meet the growing demand of this important PUFA. PMID:24788769

  6. NMR spectroscopy and perfusion of mammalian cells using surface microprobes.

    PubMed

    Ehrmann, Klaus; Pataky, Kristopher; Stettler, Matthieu; Wurm, Florian Maria; Brugger, Jürgen; Besse, Pierre-André; Popovic, Radivoje

    2007-03-01

    NMR spectra of mammalian cells are taken using surface microprobes that are based on microfabricated planar coils. The surface microprobe resembles a miniaturized Petri dish commonly used in biological research. The diameter of the planar coils is 1 mm. Chinese Hamster Ovaries are immobilized in a uniform layer on the microprobe surface or patterned by an ink-jet printer in the centre of the microcoil, where the rf-field of the planar microcoil is most uniform. The acquired NMR spectra show the prevalent metabolites found in mammalian cells. The volumes of the detected samples range from 25 nL to 1 nL (or 50,000 to 1800 cells). With an extended set-up that provides fluid inlets and outlets to the microprobe, the cells can be perfused within the NMR-magnet while constantly taking NMR spectra. Perfusion of the cells opens the way to increased cell viability for long acquisitions or to analysis of the cells' response to environmental change. PMID:17330170

  7. Lack of Rev7 function results in development of tubulostromal adenomas in mouse ovary.

    PubMed

    Abbasi, Abdolrahim; Khalaj, Maryam; Akiyama, Kouyou; Mukai, Yoshiyuki; Matsumoto, Hirokazu; Acosta, Tomas J; Said, Neveen; Yoshida, Midori; Kunieda, Tetsuo

    2015-09-01

    Rev7 is a subunit of Polζ, one of the translesion DNA synthesis (TLS) polymerases involved in DNA damage repair. We recently found that Rev7 is also essential for germ cell development in mouse. In the present study, we found the development of ovarian tumors in Rev7 mutant mouse, suggesting the involvement of TLS deficiency in the etiology of ovarian tumor. The Rev7 mutant mice showed complete lack of oocytes and follicles in the ovary. The lack of follicles causes a significant increase of gonadotropin level and an increase in the proliferation of ovarian cells. As a result, the weight of the ovaries of Rev7 mutant mice increased with age and they developed tubulostromal adenomas. However, the remarkable overgrowth of ovaries occurred after gonadotropin level decreases at older ages, suggesting gonadotropin-independent progression of the ovarian tumors. In addition, the Rev7 mutant fibroblasts and ovarian cells showed significant accumulation of DNA damage. These findings suggest that not only increased gonadotropin levels but also lack of DNA damage repair function could be responsible for the development of ovarian tumors in the Rev7 mutant mouse. PMID:26004212

  8. Development of the germinal ridge and ovary in the African elephant (Loxodonta africana).

    PubMed

    Stansfield, F J; Nöthling, J O; Soley, J T; Allen, W R

    2012-11-01

    The follicular reserve and its ontogeny in the elephant are of interest because elephants have the longest reproductive life of all land-based mammals. They also have the longest recorded pregnancy, which allows a protracted view of the series of significant events involved in the development of the embryonic and fetal gonads. The large elephant population of Zimbabwe provided the opportunity to collect conceptuses from elephants culled for management reasons and hunted professionally. Five embryos aged 76-96 days and the ovaries of four fetuses aged 4.8-11.2 months were fixed in 4% buffered formalin and studied by conventional histological sectioning and a stereological protocol to calculate the follicle reserve of each fetus. These observations enabled the conclusion that the migration of primordial germ cells into the indifferent gonad terminates at around 76 days of gestation while entry of oogonia into meiosis along with first follicle formation starts at around 5 months. Peak numbers of follicles are present by mid-gestation towards the end of the 6-month mitotic-meiotic transition period. It appears that the cortex of the elephant fetal ovary at mid-gestation (11 months) has already reached a developmental stage exhibited by the ovaries of many other mammals at full term. PMID:22991581

  9. Analysis of Phagocytosis in the Drosophila Ovary.

    PubMed

    Meehan, Tracy L; Serizier, Sandy B; Kleinsorge, Sarah E; McCall, Kimberly

    2016-01-01

    Programmed cell death (PCD) is essential for health and development. Generally, the last step of PCD is clearance, or engulfment, by phagocytes. Engulfment can be broken down into five basic steps: attraction of the phagocyte, recognition of the dying cell, internalization, phagosome maturation, and acidification of the engulfed material. The Drosophila melanogaster ovary serves as an excellent model to study diverse types of PCD and engulfment by epithelial cells. Here, we describe several methods to detect and analyze multiple steps of engulfment in the Drosophila ovary: recognition, vesicle uptake, phagosome maturation, and acidification. Annexin V detects phosphatidylserine, which is flipped to the outer leaflet of the plasma membrane of apoptotic cells, serving as an "eat me" signal. Several germline markers including tral-GFP, Orb, and cleaved Dcp-1 can all be used to label the germline and visualize its uptake into engulfing follicle cells. Drosophila strains expressing GFP and mCherry protein fusions can enable a detailed analysis of phagosome maturation. LysoTracker labels highly acidified compartments, marking phagolysosomes. Together these labels can be used to mark the progression of engulfment in Drosophila follicle cells. PMID:27557574

  10. Polycystic Ovaries Associated with Congenital Adrenal Hyperplasia

    PubMed Central

    Lucis, O. J.; Hobkirk, R.; Hollenberg, C. H.; MacDonald, S. A.; Blahey, P.

    1966-01-01

    Polycystic ovaries were found in a 16-year-old female with congenital absence of vagina, male-like external genitalia, and congenital adrenal hyperplasia. Masculinization was sufficiently severe to cause the patient to be reared as a male. Biochemical studies of ovarian tissue revealed hyperactivity and an imbalance of enzyme systems concerned with steroid-hormone biosynthesis, which led to production of large amounts of androgens. The pathway towards estrogens was preserved but less efficient than normal. Urinary steroid metabolites before and after hysterectomy and bilateral salpingo-oophorectomy revealed an absence of Porter-Silber chromogens and tetrahydrocortisone. Excretion of aldosterone was normal and that of corticosterone slightly higher than normal. The patterns of urinary 17-ketosteroids, pregnanediol, pregnanetriol and pregnanetriolone were similar to those commonly seen in congenital adrenal hyperplasia with steroid 21-hydroxylase deficiency. Urinary estrogens after panhysterectomy were low, being in the post-menopausal range. The pathogenesis of polycystic ovaries and their possible contribution to masculinization are discussed. ImagesFig. 1Fig. 2Fig. 3 PMID:5901591

  11. Gonadotropin-releasing hormone in the ovary.

    PubMed

    Metallinou, Chryssa; Asimakopoulos, Byron; Schröer, Andreas; Nikolettos, Nikos

    2007-12-01

    Gonadotropin-releasing hormone (GnRH) plays a pivotal role in the physiology of reproduction in mammals. GnRH acts by binding to the GnRH receptor (GnRHR). In humans, only 1 conventional GnRH receptor subtype (type I GnRH receptor) has been found. In the human genome, 2 forms of GnRH have been identified, GnRH-I (mammal GnRH) and GnRH-II (chicken GnRH II). Both forms and their common receptor are expressed, apart from the hypothalamus, in various compartments of the human ovary. Gonadal steroids, gonadotropins, and GnRH itself controls the regulation of the GnRH/GnRHR system gene expression in the human ovary. The 2 types of GnRH acting paracrinally/autocrinally influence ovarian steroidogenesis, decrease the proliferation, and induce apoptosis of ovarian cells. In this review, the biology of GnRH/GnRHR system in humans, the potential roles of GnRH, and the direct effects of GnRH analogues in ovarian cells are discussed. PMID:18089592

  12. Features of Polycystic Ovary Syndrome in adolescence

    PubMed Central

    Tsikouras, P; Spyros, L; Manav, B; Zervoudis, S; Poiana, C; Nikolaos, T; Petros, P; Dimitraki, M; Koukouli, C; Galazios, G; von Tempelhoff, GF

    2015-01-01

    Rationale: To elucidate the prepubertal risk factors associated with the development of Polycystic Ovary Syndrome (PCOS) and determine the special clinical manifestations of the syndrome in this transitional time of a woman’s life. Objective: To propose therapeutic targets and regimens, not only to prevent the long-term complications of the syndrome, but also to improve the self-esteem of a young girl who matures into womanhood. Methods and Results: A systematic review of literature was performed through electronic database searches (Pubmed, Medline and Embase). Studies published in English-language, peer-reviewed journals from 1996 to 2013 were included. The selected studies focused on the risk factors, the unique features and treatment options of the PCOS in puberty. The pathogenesis of the PCOS was hypothesized to be based on interactions between genetic and certain environmental factors. The diagnosis was usually difficult in young girls. The syndrome was related to a greater risk of future infertility, type II diabetes mellitus, the metabolic syndrome and cardiovascular disease. Early treatment was crucial to prevent the long-term complications of the syndrome, especially infertility and cardiovascular disease. Discussion:The recognition of the early signs of PCOS during or even before adolescence is of great importance. It is essential to establish the correct diagnosis for PCOS and rule out other causes of androgen excess in young women with hyperandrogenism. The type of treatment applied should be considered on an individual basis. Abbreviations: PCOS = Polycystic Ovary Syndrome PMID:26351529

  13. Inhibition of serotonin reuptake in the prepubertal rat ovary by fluoxetine and effects on ovarian functions.

    PubMed

    Romero-Reyes, Jessica; Cárdenas, Mario; Damián-Matsumura, Pablo; Domínguez, Roberto; Ayala, María Elena

    2016-01-01

    Fluoxetine (FLX), a selective serotonin reuptake inhibitor is an antidepressant in the treatment of mood disorders. Its impact on reproductive processes is incompletely known. The present study analyzed the reproductive effects of FLX in prepubertal female rats. Two experiments were conducted. First (acute administration), 30-day-old female rats were injected intraperitoneally with 5mg/kg of fluoxetine-hydrochloride, and were terminated 24, 48 or 72h after the treatment. Second (subchronic administration), FLX was injected on days 30-33 of age, and the animals were terminated the day of first estrus. In acute treatment estradiol concentration increased to 72h. In subchronic treatment increased serotonin concentration in ovaries and decreased the number of ova shed. An increase in number of atretic follicles and oocyte fragmentation was observed in these animals. The results suggest that FLX acts on the ovary or hypothalamus-pituitary axis resulting in modifications of the follicular development and ovulation. PMID:26746107

  14. Inguinal Hernia Containing Uterus, Fallopian Tube, and Ovary in a Premature Newborn

    PubMed Central

    Karadeniz Cerit, Kıvılcım; Ergelen, Rabia; Colak, Emel; Dagli, Tolga E.

    2015-01-01

    A female infant weighing 2,200 g was delivered at 34 weeks of gestation by vaginal delivery. She presented with an irreducible mass in the left inguinal region at 32 days of age. An ultrasonography (US) was performed and an incarcerated hernia containing uterus, fallopian tube, and ovary was diagnosed preoperatively. Surgery was performed through an inguinal approach; the uterus, fallopian tube, and ovary were found in the hernia sac. High ligation and an additional repair of the internal inguinal ring were performed. Patent processus vaginalis was found during contralateral exploration and also closed. The postoperative course was uneventful. After one year of follow-up, there have been no signs of recurrence. PMID:26351609

  15. FACS-sorted putative oogonial stem cells from the ovary are neither DDX4-positive nor germ cells

    PubMed Central

    Zarate-Garcia, Larissa; Lane, Simon I. R.; Merriman, Julie A.; Jones, Keith T.

    2016-01-01

    Whether the adult mammalian ovary contains oogonial stem cells (OSCs) is controversial. They have been isolated by a live-cell sorting method using the germ cell marker DDX4, which has previously been assumed to be cytoplasmic, not surface-bound. Furthermore their stem cell and germ cell characteristics remain disputed. Here we show that although OSC-like cells can be isolated from the ovary using an antibody to DDX4, there is no good in silico modelling to support the existence of a surface-bound DDX4. Furthermore these cells when isolated were not expressing DDX4, and did not initially possess germline identity. Despite these unremarkable beginnings, they acquired some pre-meiotic markers in culture, including DDX4, but critically never expressed oocyte-specific markers, and furthermore were not immortal but died after a few months. Our results suggest that freshly isolated OSCs are not germ stem cells, and are not being isolated by their DDX4 expression. However it may be that culture induces some pre-meiotic markers. In summary the present study offers weight to the dogma that the adult ovary is populated by a fixed number of oocytes and that adult de novo production is a rare or insignificant event. PMID:27301892

  16. FACS-sorted putative oogonial stem cells from the ovary are neither DDX4-positive nor germ cells.

    PubMed

    Zarate-Garcia, Larissa; Lane, Simon I R; Merriman, Julie A; Jones, Keith T

    2016-01-01

    Whether the adult mammalian ovary contains oogonial stem cells (OSCs) is controversial. They have been isolated by a live-cell sorting method using the germ cell marker DDX4, which has previously been assumed to be cytoplasmic, not surface-bound. Furthermore their stem cell and germ cell characteristics remain disputed. Here we show that although OSC-like cells can be isolated from the ovary using an antibody to DDX4, there is no good in silico modelling to support the existence of a surface-bound DDX4. Furthermore these cells when isolated were not expressing DDX4, and did not initially possess germline identity. Despite these unremarkable beginnings, they acquired some pre-meiotic markers in culture, including DDX4, but critically never expressed oocyte-specific markers, and furthermore were not immortal but died after a few months. Our results suggest that freshly isolated OSCs are not germ stem cells, and are not being isolated by their DDX4 expression. However it may be that culture induces some pre-meiotic markers. In summary the present study offers weight to the dogma that the adult ovary is populated by a fixed number of oocytes and that adult de novo production is a rare or insignificant event. PMID:27301892

  17. Cardiovascular risk in women with polycystic ovary syndrome.

    PubMed

    Giallauria, Francesco; Orio, Francesco; Palomba, Stefano; Lombardi, Gaetano; Colao, Annamaria; Vigorito, Carlo

    2008-10-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous disease affecting about 5-10% of reproductive-age female population, which is predominantly characterized by chronic anovulation, hyperandrogenism and insulin resistance. PCOS women represent an intriguing biological model illustrating the relationship between hormonal pattern and cardiovascular risk profile, presenting a cluster of cardiovascular features, such as obesity, insulin resistance, hypertension, impaired cardiopulmonary functional capacity, autonomic dysfunction and low-grade chronic inflammation. Metabolic syndrome should be also considered in the clinical evaluation and management of PCOS. The treatment of PCOS and its complications should not be based solely on pharmacological therapies trying to improve hyperandrogenism, hyperinsulinemia and insulin resistance. Although mounting evidence recognizes the beneficial effects of lifestyle modifications, the clinical management of PCOS is not sufficiently focused on long-term maintenance of both exercise and dietary interventions and on further aspects of this syndrome (i.e. psychological status). Taking into consideration the patients' young age and the devastating effects of PCOS on hormonal and metabolic pattern, this complex and multifaceted disease requires a comprehensive approach in order to achieve concrete beneficial effects for PCOS patients. Multidisciplinary programs, including dietary and educational counseling, exercise training, stress management and psychosocial support, might represent the gold standard for adequate reduction of cardiovascular risk in young women with PCOS. PMID:18799960

  18. Unilateral or bilateral vagotomy induces ovulation in both ovaries of rats with polycystic ovarian syndrome

    PubMed Central

    2013-01-01

    Background Injecting estradiol valerate (EV) to pre-pubertal or adult female rat results in effects similar to those observed in women with polycystic ovarian syndrome (PCOS). One of the mechanisms involved in PCOS development is the hyperactivity of the sympathetic nervous system. In EV-induced PCOS rats, the unilateral sectioning of the superior ovarian nerve (SON) restores ovulation of the innervated ovary. This suggests that, in addition to the sympathetic innervation, other neural mechanisms are involved in the development/maintenance of PCOS. The aims of present study were analyze if the vagus nerve is one of the neural pathways participating in PCOS development. Methods Ten-day old rats were injected with EV dissolved in corn oil. At 24-days of age sham-surgery, unilateral, or bilateral sectioning of the vagus nerve (vagotomy) was performed on these rats. The animals were sacrificed at 90–92 days of age, when they presented vaginal estrous preceded by a pro-estrus smear. Results In EV-induced PCOS rats, unilateral or bilateral vagotomy restored ovulation in both ovaries. Follicle-stimulating hormone (FSH) levels in PCOS rats with unilateral or bilateral vagotomy were lower than in control rats. Conclusions This result suggests that in EV-induced PCOS rats the vagus nerve is a neural pathway participating in maintaining PCOS. The vagus nerve innervates the ovaries directly and indirectly through its synapsis in the celiac-superior-mesenteric ganglion, where the somas of neurons originating in the SON are located. Then, it is possible that vagotomy effects in EV-induced PCOS rats may be explained as a lack of communication between the central nervous system and the ovaries. PMID:23866168

  19. Electroporation into Cultured Mammalian Embryos

    NASA Astrophysics Data System (ADS)

    Nomura, Tadashi; Takahashi, Masanori; Osumi, Noriko

    Over the last century, mammalian embryos have been used extensively as a common animal model to investigate fundamental questions in the field of developmental biology. More recently, the establishment of transgenic and gene-targeting systems in laboratory mice has enabled researchers to unveil the genetic mechanisms under lying complex developmental processes (Mak, 2007). However, our understanding of cell—cell interactions and their molecular basis in the early stages of mammalian embryogenesis is still very fragmentary. One of the major problems is the difficulty of precise manipulation and limited accessibility to mammalian embryos via uterus wall. Unfortunately, existing tissue and organotypic culture systems per se do not fully recapitulate three-dimensional, dynamic processes of organogenesis observed in vivo. Although transgenic animal technology and virus-mediated gene delivery are useful to manipulate gene expression, these techniques take much time and financial costs, which limit their use.

  20. Psychological aspects of the polycystic ovary syndrome.

    PubMed

    Farkas, Judit; Rigó, Adrien; Demetrovics, Zsolt

    2014-02-01

    An overwhelming majority of scientific literature on the polycystic ovary syndrome has utilized a medical approach to analyse the disorder and only few studies have investigated its predisposing psychological factors. This literature review sheds light on the fact that this gynaecological disorder of endocrine origin, which is becoming more frequent, can be associated with a great number of psychological symptoms (e.g. depression, anxiety, body image dissatisfaction, eating and sexual disorders, and low life satisfaction). Thus, the syndrome is significant from a therapeutic point of view as well. Authors review the psychological correlates of specific symptoms, their relationships with other psychological syndromes and analyse the psychosocial background of the disorder as well as the possibilities of psychotherapy. PMID:24188448

  1. Overexpression of microRNAs enhances recombinant protein production in Chinese hamster ovary cells.

    PubMed

    Loh, Wan Ping; Loo, Bernard; Zhou, Lihan; Zhang, Peiqing; Lee, Dong-Yup; Yang, Yuansheng; Lam, Kong Peng

    2014-09-01

    MicroRNAs (miRNAs) are short, non-coding RNAs that can negatively regulate expression of multiple genes at post-transcriptional levels. Using miRNAs to target multiple genes and pathways is a promising cell-engineering strategy to increase recombinant protein production in mammalian cells. Here, we identified miRs-17, -19b, -20a, and -92a to be differentially expressed between high- and low- monoclonal antibody-producing Chinese hamster ovary (CHO) cell clones using next-generation sequencing and quantitative real-time PCR. These miRNAs were stably overexpressed individually and in combination in a high-producing clone to assess their effects on CHO cell growth, recombinant protein productivity and product quality. Stably transfected pools demonstrated 24-34% increases in specific productivity (qP) and 21-31% increases in titer relative to the parental clone, without significant alterations in proliferation rates. The highest protein-producing clones isolated from these pools exhibited 130-140% increases in qP and titer compared to the parental clone, without major changes in product aggregation and N-glycosylation profile. From our clonal data, correlations between enhanced qP/titer and increased levels of miRs-17, -19b, and -92a were observed. Our results demonstrate the potential of miRs-17, -19b, and -92a as cell-engineering targets to increase recombinant protein production in mammalian cells. PMID:24819042

  2. Estrogen-Dependent Gene Expression in the Mouse Ovary

    PubMed Central

    Liew, Seng H.; Sarraj, Mai A.; Drummond, Ann E.; Findlay, Jock K.

    2011-01-01

    Estrogen (E) plays a pivotal role in regulating the female reproductive system, particularly the ovary. However, the number and type of ovarian genes influenced by estrogen remain to be fully elucidated. In this study, we have utilized wild-type (WT) and aromatase knockout (ArKO; estrogen free) mouse ovaries as an in vivo model to profile estrogen dependent genes. RNA from each individual ovary (n = 3) was analyzed by a microarray-based screen using Illumina Sentrix Mouse WG-6 BeadChip (45,281 transcripts). Comparative analysis (GeneSpring) showed differential expression profiles of 450 genes influenced by E, with 291 genes up-regulated and 159 down-regulated by 2-fold or greater in the ArKO ovary compared to WT. Genes previously reported to be E regulated in ArKO ovaries were confirmed, in addition to novel genes not previously reported to be expressed or regulated by E in the ovary. Of genes involved in 5 diverse functional processes (hormonal processes, reproduction, sex differentiation and determination, apoptosis and cellular processes) 78 had estrogen-responsive elements (ERE). These analyses define the transcriptome regulated by E in the mouse ovary. Further analysis and investigation will increase our knowledge pertaining to how E influences follicular development and other ovarian functions. PMID:21347412

  3. Computer-Generated Ovaries to Assist Follicle Counting Experiments

    PubMed Central

    Skodras, Angelos; Marcelli, Gianluca

    2015-01-01

    Precise estimation of the number of follicles in ovaries is of key importance in the field of reproductive biology, both from a developmental point of view, where follicle numbers are determined at specific time points, as well as from a therapeutic perspective, determining the adverse effects of environmental toxins and cancer chemotherapeutics on the reproductive system. The two main factors affecting follicle number estimates are the sampling method and the variation in follicle numbers within animals of the same strain, due to biological variability. This study aims at assessing the effect of these two factors, when estimating ovarian follicle numbers of neonatal mice. We developed computer algorithms, which generate models of neonatal mouse ovaries (simulated ovaries), with characteristics derived from experimental measurements already available in the published literature. The simulated ovaries are used to reproduce in-silico counting experiments based on unbiased stereological techniques; the proposed approach provides the necessary number of ovaries and sampling frequency to be used in the experiments given a specific biological variability and a desirable degree of accuracy. The simulated ovary is a novel, versatile tool which can be used in the planning phase of experiments to estimate the expected number of animals and workload, ensuring appropriate statistical power of the resulting measurements. Moreover, the idea of the simulated ovary can be applied to other organs made up of large numbers of individual functional units. PMID:25812007

  4. [The polycystic ovary syndrome and insulin resistance].

    PubMed

    Kreze, A; Hrnciar, J; Dobáková, M; Pekarová, E

    1997-10-01

    The insulin resistance syndrome and the polycystic ovary syndrome (PCOS) appear to have some following coincidences: the existence of subclinical acanthosis nigricans in PCOS hyperinsulinemic women, correlation of insulin levels and free testosterone, insulin-like growth factor I binding protein (IGFIBP), and sex-hormone binding globulin. Insulin and IGFI act synergically with luteinizing hormone increasing the activity of cytochrome P450c17 and its enzymatic activity in the adrenals. The decrease in IGFI level and IGFI receptors in the ovarian granulosa cells reduce the steroids aromatisation. The increased expression of IGFI receptors in the theca cells favours the androgens' synthesis. Long-term insulin therapy results in an increase in ovary volume and the blood androgens levels. The deterioration of insulin resistance in PSOC women progresses also by the reduction of type I of skeletal muscle fibres which are sensitive to insulin, and the increase of type II fibres which are resistant to insulin in hyperandrogenemia. Testosterone deteriorates the skeletal as well as hepatic insulin sensitivity by both its facilitating effect on lipolysis and the increase of free fatty acids. Abdominal obesity seen in PCOS and insulin resistance is composed by adipocytes with glucocorticoid receptors, which after cortisol stimulation activate the lipoprotein lipase and fat accumulation. Gynoid obesity with the preferential aromatisation of steroids is not evolved because of the low estrogens and progesterone levels in PCOS. Low progesterone levels (with anticortisol effect) support the development of abdominal obesity. Ultimately, the early peak of insulin secretion (4-8 min) in PCOS is higher. This fact should testify a certain diabetic disposition. (Ref. 37.) PMID:9490171

  5. Alpha smooth muscle actin in the cycling ovary - an immunohistochemical study.

    PubMed

    Hirschberg, Ruth M; Plendl, Johanna; Kaessmeyer, Sabine

    2012-01-01

    In the ovary with its cyclically developing and regressing functional bodies and the associated intense neovascularisation and remodelling, alpha-smooth muscle actin (SMA) immunolocalisation has been frequently used as a marker to establish vessel hierarchy, in angiogenesis studies, or in studies characterising ovarian neoplasms in various species. The present study aims at detection of alpha-SMA-immunolocalisation within all structural components of the cycling bovine ovary in order to complement the hitherto available data. 27 ovaries, mainly of dairy cows ranging from 23 to 118 months of age and displaying all major stages of follicle and corpora lutea development, were collected at the abattoir and subjected to routine HE and trichrome staining as well as alpha-SMA immunohistochemistry. For this purpose, the specimens were pooled to form groups of the respective stage of corpus luteum development. The ovarian stroma displayed a notable alpha-SMA-reactivity, particularly surrounding the functional bodies. The study revealed specialised vascular modifications such as multi-directionally arranged vascular smooth muscle layers, vascular sphincters and distinct epitheloid modifications of the media in ovarian arteries. Alpha-SMA-reactivity of the microcirculation within corpora lutea of various stages allowed inferences on respective angiogenic properties. The findings were discussed focussing on functional interpretations. PMID:22538540

  6. Ultrastructural Analysis of Drosophila Ovaries by Electron Microscopy

    PubMed Central

    Hurd, Thomas R.; Sanchez, Carlos G.; Teixeira, Felipe K.; Petzold, Chris; Dancel-Manning, Kristen; Wang, Ju-Yu S.; Lehmann, Ruth; Liang, Feng-Xia A.

    2016-01-01

    i. Summary The Drosophila melanogaster ovary is a powerful, genetically tractable system through which one can elucidate the principles underlying cellular function and organogenesis in vivo. In order to understand the intricate process of oogenesis at the subcellular level, microscopic analysis with the highest possible resolution is required. In this chapter, we describe the preparation of ovaries for ultrastructural analysis using transmission electron microscopy and focused ion beam scanning electron microscopy. We discuss and provide protocols for chemical fixation of Drosophila ovaries that facilitate optimal imaging with particular attention paid to preserving and resolving mitochondrial membrane morphology and structure. PMID:26324436

  7. Bilateral Cystic Lymphangioma of Ovary Associated with Chylous Ascites

    PubMed Central

    Arakeri, Surekha Ulhas; Patil, Vijaya L.; Mulay, Himanshu Dilip

    2015-01-01

    Intraabdominal cystic lymphangiomas are rare and are located in retroperitoneum, mesentery, omentum and other visceral organs. Lymphangiomas of the ovary are rare and are usually unilateral. Cases with bilateral cystic lymphangiomas of the ovary are reported very rarely in literature. We report a rare case of bilateral cystic lymphangioma of ovary associated with chylous ascites in a 35-year-old lady who presented with complaints of severe dysmenorrhoea and oligomenorrhoea since 6 months with history of chyluria for the past 3 years. PMID:26435959

  8. Ultrastructural Analysis of Drosophila Ovaries by Electron Microscopy.

    PubMed

    Hurd, Thomas R; Sanchez, Carlos G; Teixeira, Felipe K; Petzold, Chris; Dancel-Manning, Kristen; Wang, Ju-Yu S; Lehmann, Ruth; Liang, Feng-Xia A

    2015-01-01

    The Drosophila melanogaster ovary is a powerful, genetically tractable system through which one can elucidate the principles underlying cellular function and organogenesis in vivo. In order to understand the intricate process of oogenesis at the subcellular level, microscopic analysis with the highest possible resolution is required. In this chapter, we describe the preparation of ovaries for ultrastructural analysis using transmission electron microscopy and focused ion beam scanning electron microscopy. We discuss and provide protocols for chemical fixation of Drosophila ovaries that facilitate optimal imaging with particular attention paid to preserving and resolving mitochondrial membrane morphology and structure. PMID:26324436

  9. DNA repair in mammalian embryos.

    PubMed

    Jaroudi, Souraya; SenGupta, Sioban

    2007-01-01

    Mammalian cells have developed complex mechanisms to identify DNA damage and activate the required response to maintain genome integrity. Those mechanisms include DNA damage detection, DNA repair, cell cycle arrest and apoptosis which operate together to protect the conceptus from DNA damage originating either in parental gametes or in the embryo's somatic cells. DNA repair in the newly fertilized preimplantation embryo is believed to rely entirely on the oocyte's machinery (mRNAs and proteins deposited and stored prior to ovulation). DNA repair genes have been shown to be expressed in the early stages of mammalian development. The survival of the embryo necessitates that the oocyte be sufficiently equipped with maternal stored products and that embryonic gene expression commences at the correct time. A Medline based literature search was performed using the keywords 'DNA repair' and 'embryo development' or 'gametogenesis' (publication dates between 1995 and 2006). Mammalian studies which investigated gene expression were selected. Further articles were acquired from the citations in the articles obtained from the preliminary Medline search. This paper reviews mammalian DNA repair from gametogenesis to preimplantation embryos to late gestational stages. PMID:17141556

  10. Low-grade serous carcinoma of the ovary or peritoneum.

    PubMed

    Gershenson, D M

    2016-04-01

    Over the past decade, the strategy for clinical trial design in making progress against epithelial cancers of the ovary/peritoneum/fallopian tube has changed dramatically. The NRG (GOG) Rare Tumor Committee has been a leader in this transformation. No longer does 'one size fit all'. Rather, separate clinical trials for rare subtypes have been developed and, in some cases, completed. An enhanced understanding of their pathologic diagnosis, molecular biology, and clinical behavior has galvanized this change. Low-grade serous carcinoma may occur de novo or following an initial diagnosis of serous tumor of low malignant potential. It is characterized by young age at diagnosis, relative chemoresistance, and prolonged survival compared with high-grade serous carcinoma. Historically, conventional chemotherapy has demonstrated very limited activity in this subtype. Hormonal therapy may provide benefit in this subtype. Preclinical studies have identified and elucidated genes and pathways-MAP kinase pathway, IGF1-R, the angiogenesis pathway, and possibly, the PI3K/AKT/mTOR pathway in low-grade serous carcinoma. To date, clinical evidence supports the activity of MEK and BRAF inhibitors and bevacizumab. Further pursuit of targeted therapy trials is clearly warranted. PMID:27141071

  11. Association between Polycystic Ovary Syndrome and Gut Microbiota

    PubMed Central

    Guo, Yanjie; Qi, Yane; Yang, Xuefei; Zhao, Lihui; Wen, Shu; Liu, Yinhui; Tang, Li

    2016-01-01

    Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. It is difficult to treat PCOS because of its complex etiology and pathogenesis. Here, we characterized the roles of gut microbiota on the pathogenesis and treatments in letrozole (a nonsteroidal aromatase inhibitor) induced PCOS rat model. Changes in estrous cycles, hormonal levels, ovarian morphology and gut microbiota by PCR-DGGE and real-time PCR were determined. The results showed that PCOS rats displayed abnormal estrous cycles with increasing androgen biosynthesis and exhibited multiple large cysts with diminished granulosa layers in ovarian tissues. Meanwhile, the composition of gut microbiota in letrozole-treated rats was different from that in the controls. Lactobacillus, Ruminococcus and Clostridium were lower while Prevotella was higher in PCOS rats when compared with control rats. After treating PCOS rats with Lactobacillus and fecal microbiota transplantation (FMT) from healthy rats, it was found that the estrous cycles were improved in all 8 rats in FMT group, and in 6 of the 8 rats in Lactobacillus transplantation group with decreasing androgen biosynthesis. Their ovarian morphologies normalized. The composition of gut microbiota restored in both FMT and Lactobacillus treated groups with increasing of Lactobacillus and Clostridium, and decreasing of Prevotella. These results indicated that dysbiosis of gut microbiota was associated with the pathogenesis of PCOS. Microbiota interventions through FMT and Lactobacillus transplantation were beneficial for the treatments of PCOS rats. PMID:27093642

  12. Metabolic dysfunction in obese Hispanic women with polycystic ovary syndrome

    PubMed Central

    Sam, Susan; Scoccia, Bert; Yalamanchi, Sudha; Mazzone, Theodore

    2015-01-01

    STUDY QUESTION Are certain ethnic groups with polycystic ovary syndrome (PCOS) at increased risk of metabolic disorders? SUMMARY ANSWER Obese Hispanic women with PCOS are at increased risk of metabolic disorders compared with age- and BMI-matched obese non-Hispanic white women with PCOS in the USA. WHAT IS KNOWN ALREADY Ethnic differences in body composition and metabolic risk are well established. PCOS is a common disorder in women of reproductive age and is associated with high rates of insulin resistance, glucose intolerance and dyslipidemia. STUDY DESIGN, SIZE, DURATION A cross-sectional observational study was performed at an Academic Medical Center on 60 women of reproductive age with PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS Blood was obtained after fasting from 17 Hispanic, 22 non-Hispanic black and 21 non-Hispanic white women with PCOS who were similar in age and BMI. Anthropometric parameters, insulin, lipid and lipoprotein levels (measured by nuclear magnetic resonance) were compared between the three groups. MAIN RESULTS AND THE ROLE OF CHANCE Age and BMI did not differ between the groups. Hispanic women with PCOS had higher waist-to-hip ratio (WHR) (P = 0.02), homeostasis model assessment of insulin resistance (HOMA-IR) (P = 0.03) and a more atherogenic lipid and lipoprotein profile consisting of lower high-density lipoprotein (HDL) (P = 0.02), higher low-density lipoprotein (LDL) particle number (P = 0.02), higher very low-density lipoprotein particle (VLDL) size (P = 0.03) and lower LDL (P = 0.03) and HDL particle size (P = 0.005) compared with non-Hispanic white women. The differences in HDL, HOMA-IR, VLDL and LDL size did not persist after adjustment for WHR while differences in LDL particle number (P = 0.04) and HDL size (P = 0.01) persisted. LIMITATIONS, REASON FOR CAUTION The sample size for the three groups was small but the findings were still significant. The women were mostly obese so the ethnic differences in metabolic disorders may

  13. Is Ovary Removal Tied to Colon Cancer Risk?

    MedlinePlus

    ... latter group included women who'd had a hysterectomy, but no clear indication that the ovaries had ... Health News Related MedlinePlus Health Topics Colorectal Cancer Hysterectomy Ovarian Disorders About MedlinePlus Site Map FAQs Contact ...

  14. Mucin-producing tumors of the ovary: MR imaging appearance.

    PubMed

    Laurent, P-E; Thomassin-Piana, J; Jalaguier-Coudray, A

    2015-11-01

    Mucin-producing tumors of the ovary can be either primary epithelial mucin-producing tumors or ovarian metastases from a remote adenocarcinoma usually originating from the gastrointestinal tract. The purpose of this pictorial review is to describe the main types of primary or secondary mucin-producing tumors of the ovary and to provide MR imaging diagnostic criteria in order to guide further therapy. PMID:25753545

  15. Mammalian telomeres and their partnership with lamins

    PubMed Central

    Burla, Romina; La Torre, Mattia; Saggio, Isabella

    2016-01-01

    ABSTRACT Chromosome ends are complex structures, which require a panel of factors for their elongation, replication, and protection. We describe here the mechanics of mammalian telomeres, dynamics and maintainance in relation to lamins. Multiple biochemical connections, including association of telomeres to the nuclear envelope and matrix, of telomeric proteins to lamins, and of lamin-associated proteins to chromosome ends, underline the interplay between lamins and telomeres. Paths toward senescence, such as defective telomere replication, altered heterochromatin organization, and impaired DNA repair, are common to lamins' and telomeres' dysfunction. The convergence of phenotypes can be interpreted through a model of dynamic, lamin-controlled functional platforms dedicated to the function of telomeres as fragile sites. The features of telomeropathies and laminopathies, and of animal models underline further overlapping aspects, including the alteration of stem cell compartments. We expect that future studies of basic biology and on aging will benefit from the analysis of this telomere-lamina interplay. PMID:27116558

  16. Chemical analysis of individual mammalian cells

    SciTech Connect

    Tan, W.; Yeung, E.S.

    1994-12-31

    The extremely small size of mammalian cells creates an unusual challenge for the analytical chemist, both in terms of separation and detection. Under a microscope, it is possible to confirm the injection of individual cells such as erythrocyte into capillaries with 10-{mu}m i.d. by hydrostatic pressure. The ionic contents can then be separated by capillary electrophoresis after the cell lyses. Enzymes at the zeptomole level can be monitored by on-column fluorescence enzyme assay. On-column particle-counting immunoassay can be applied to a broad range of analytes (antigens), also at the zeptomole level. The authors report here the simultaneous determination of the amounts of glucose-6-phosphate dehydrogenase (G6PDH) and their activities in individual erythrocytes by using a combination of the two detection schemes. Insights into the degradation of proteins as a function of cell age can be derived.

  17. Pattern of human chorionic gonadotropin binding in the polycystic ovary

    SciTech Connect

    Brawer, J.; Richard, M.; Farookhi, R. )

    1989-08-01

    The histologic evolution of polycystic ovaries in the estradiol valerate-treated rat coincides with the development of a unique plasma pattern of luteinizing hormone. To assess the role of luteinizing hormone in polycystic ovaries, it is necessary to evaluate the luteinizing hormone sensitivity of the specific tissues in the polycystic ovary. Therefore, we examined the pattern of luteinizing hormone binding sites in polycystic ovaries. Rats at 4 or 8 weeks after estradiol valerate treatment each received an intrajugular injection of iodine 125-labeled human chorionic gonadotropin. Some rats also received a 1000-fold excess of unlabeled human chorionic gonadotropin in the same injection. Ovaries were prepared for autoradiography. Dense accumulations of grains occurred over the theca of normal and atretic secondary follicles in all ovaries and over clusters of secondary interstitial cells. The iodine label was variable over the typically hypertrophied theca of precystic follicles. The theca of definitive cysts showed little or no label. These results indicate that cyst formation coincides with the loss of luteinizing hormone/human chorionic gonadotropin binding to the affected follicles.

  18. Co-expression of cytokeratin and vimentin filaments in mesothelial, granulosa and rete ovarii cells of the human ovary.

    PubMed

    Czernobilsky, B; Moll, R; Levy, R; Franke, W W

    1985-05-01

    The intermediate filament (IF) system of the various cells of human, pig and rat ovaries was studied by electron microscopy, by immunolocalization using antibodies to cytokeratins, vimentin, desmin and desmoplakin, and by two-dimensional gel electrophoresis of cytoskeletal proteins from microdissected tissue samples. In human ovaries, surface epithelial cells (mesothelium) were stained by antibodies against cytokeratins, desmoplakins and vimentin. Biochemical analysis revealed cytokeratins Nos. 8, 18 and 19, together with variable amounts of No. 7. Granulosa cells of follicles of all stages were also positive for cytokeratins, desmoplakins and vimentin, in agreement with the electron microscopic finding of desmosomes in these cells. As the follicle matured, the cytokeratin content usually appeared to decrease, whereas vimentin remained unchanged. On gel electrophoresis, granulosa cells presented cytokeratins Nos. 8 and 18 and vimentin. Rete ovarii cells were also positive for both cytokeratins, desmoplakins and vimentin, and the electron microscopy revealed numerous desmosome-tonofilament complexes. Oocytes appeared to be devoid of IFs. Corpus luteum cells were rich in vimentin but biochemical analysis also revealed small amounts of cytokeratins Nos. 8 and 18. In contrast, cells of the ovarian stroma and luteinized stromal nodules were positive for vimentin only. A certain type of scattered stromal cells, especially around tertiary follicles and corpora lutea, and also desmin-positive. Pig and rat ovaries differed from human ones in that vimentin was not detected in ovarian mesothelium and cytokeratins were not seen in granulosa cells. The latter, however, contained significant amounts of vimentin. These results indicate that three cell types of human ovary, i.e. surface epithelial, granulosa and rete ovarii cells, can be regarded as true epithelial cells which, however, simultaneously express vimentin, a phenomenon frequently seen in cultured epithelial cells but

  19. Mechanisms of mammalian iron homeostasis

    PubMed Central

    Pantopoulos, Kostas; Porwal, Suheel Kumar; Tartakoff, Alan; Devireddy, L.

    2012-01-01

    Iron is vital for almost all organisms because of its ability to donate and accept electrons with relative ease. It serves as a cofactor for many proteins and enzymes necessary for oxygen and energy metabolism, as well as for several other essential processes. Mammalian cells utilize multiple mechanisms to acquire iron. Disruption of iron homeostasis is associated with various human diseases: iron deficiency resulting from defects in acquisition or distribution of the metal causes anemia; whereas iron surfeit resulting from excessive iron absorption or defective utilization causes abnormal tissue iron deposition, leading to oxidative damage. Mammals utilize distinct mechanisms to regulate iron homeostasis at the systemic and cellular levels. These involve the hormone hepcidin and iron regulatory proteins, which collectively ensure iron balance. This review outlines recent advances in iron regulatory pathways, as well as in mechanisms underlying intracellular iron trafficking, an important but less-studied area of mammalian iron homeostasis. PMID:22703180

  20. An overview of mammalian pluripotency.

    PubMed

    Wu, Jun; Yamauchi, Takayoshi; Izpisua Belmonte, Juan Carlos

    2016-05-15

    Mammalian pluripotency is the ability to give rise to all somatic cells as well as the germ cells of an adult mammal. It is a unique feature of embryonic epiblast cells, existing only transiently, as cells pass through early developmental stages. By contrast, pluripotency can be captured and stabilized indefinitely in cell culture and can also be reactivated in differentiated cells via nuclear reprogramming. Pluripotent stem cells (PSCs) are the in vitro carriers of pluripotency and they can inhabit discrete pluripotent states depending on the stage at which they were derived and their culture conditions. Here, and in the accompanying poster, we provide a summary of mammalian pluripotency both in vivo and in vitro, and highlight recent and future applications of PSCs for basic and translational research. PMID:27190034

  1. Diagnosis and treatment of polycystic ovary syndrome (PCOS): an interview with Richard Legro.

    PubMed

    Legro, Richard

    2015-01-01

    In this podcast, we talk to Professor Richard Legro about the recommendations for the diagnosis and treatment of polycystic ovary syndrome (PCOS) based on clinical practice guidelines and discuss the challenges of diagnosis PCOS at specific age groups. The controversies associated with treatment of PCOS, including therapies for infertility as this is a problem commonly observed in PCOS subjects, are highlighted together with future directions on the topic. The podcast for this interview is available at. http://www.biomedcentral.com/content/supplementary/s12916-015-0299-2-s1.mp3. PMID:25879641

  2. Proteomic Analysis of Chinese Hamster Ovary Cells

    PubMed Central

    Baycin-Hizal, Deniz; Tabb, David L.; Chaerkady, Raghothama; Chen, Lily; Lewis, Nathan E.; Nagarajan, Harish; Sarkaria, Vishaldeep; Kumar, Amit; Wolozny, Daniel; Colao, Joe; Jacobson, Elena; Tian, Yuan; O'Meally, Robert N.; Krag, Sharon S.; Cole, Robert N.; Palsson, Bernhard O.; Zhang, Hui; Betenbaugh, Michael

    2013-01-01

    In order to complement the recent genomic sequencing of Chinese hamster ovary (CHO) cells, proteomic analysis was performed on CHO including the cellular proteome, secretome, and glycoproteome using tandem mass spectrometry (MS/MS) of multiple fractions obtained from gel electrophoresis, multi-dimensional liquid chromatography, and solid phase extraction of glycopeptides (SPEG). From the 120 different mass spectrometry analyses generating 682,097 MS/MS spectra, 93,548 unique peptide sequences were identified with at most a 0.02 false discovery rate (FDR). A total of 6164 grouped proteins were identified from both glycoproteome and proteome analysis, representing an 8-fold increase in the number of proteins currently identified in the CHO proteome. Furthermore, this is the first proteomic study done using CHO genome exclusively which provides for more accurate identification of proteins. From this analysis, the CHO codon frequency was determined and found to be distinct from humans, which will facilitate expression of human proteins in CHO cells. Analysis of the combined proteomic and mRNA data sets indicated the enrichment of a number of pathways including protein processing and apoptosis but depletion of proteins involved in steroid hormone and glycosphingolipid metabolism. 504 of the detected proteins included N-acetylation modifications and 1292 different proteins were observed to be N-glycosylated. This first large-scale proteomic analysis will enhance the knowledge base about CHO capabilities for recombinant expression and provide information useful in cell engineering efforts aimed at modifying CHO cellular functions. PMID:22971049

  3. Cognitive functioning in polycystic ovary syndrome.

    PubMed

    Barnard, L; Balen, A H; Ferriday, D; Tiplady, B; Dye, L

    2007-01-01

    To date there have been no published studies of cognitive functioning in polycystic ovary syndrome (PCOS). This large internet-based study compared neuropsychological functioning in right-handed women with (minimum n=135) and without PCOS (minimum n=322), stratified according to use of anti-androgen medication and level of depression. Women with PCOS are thought to have hyperandrogenism and hyperestrogenism which was hypothesized to differentially influence cognitive function across cognitive domains. Performance did not differ according to diagnosis on mental rotation and spatial location tasks. Hence, no evidence to support the view that women with PCOS display a more masculine cognitive profile due to hyperandrogenism. Despite presumed hyperestrogenism, women with PCOS demonstrated impaired performance in terms of speed and accuracy, on reaction time and word recognition tasks. These findings are intriguing given the well-documented roles of estrogen and testosterone in cognitive function. Overall, these findings suggest that PCOS is not associated with masculinized cognitive functioning, and, although associated with impaired performance on tasks considered to demonstrate female-advantage, such impairments are subtle and are unlikely to affect daily functioning. PMID:17659845

  4. Treatment options for polycystic ovary syndrome

    PubMed Central

    Badawy, Ahmed; Elnashar, Abubaker

    2011-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. The clinical manifestation of PCOS varies from a mild menstrual disorder to severe disturbance of reproductive and metabolic functions. Management of women with PCOS depends on the symptoms. These could be ovulatory dysfunction-related infertility, menstrual disorders, or androgen-related symptoms. Weight loss improves the endocrine profile and increases the likelihood of ovulation and pregnancy. Normalization of menstrual cycles and ovulation could occur with modest weight loss as little as 5% of the initial weight. The treatment of obesity includes modifications in lifestyle (diet and exercise) and medical and surgical treatment. In PCOS, anovulation relates to low follicle-stimulating hormone concentrations and the arrest of antral follicle growth in the final stages of maturation. This can be treated with medications such as clomiphene citrate, tamoxifen, aromatase inhibitors, metformin, glucocorticoids, or gonadotropins or surgically by laparoscopic ovarian drilling. In vitro fertilization will remain the last option to achieve pregnancy when others fail. Chronic anovulation over a long period of time is also associated with an increased risk of endometrial hyperplasia and carcinoma, which should be seriously investigated and treated. There are androgenic symptoms that will vary from patient to patient, such as hirsutism, acne, and/or alopecia. These are troublesome presentations to the patients and require adequate treatment. Alternative medicine has been emerging as one of the commonly practiced medicines for different health problems, including PCOS. This review underlines the contribution to the treatment of different symptoms. PMID:21339935

  5. Proteomic analysis of Chinese hamster ovary cells.

    PubMed

    Baycin-Hizal, Deniz; Tabb, David L; Chaerkady, Raghothama; Chen, Lily; Lewis, Nathan E; Nagarajan, Harish; Sarkaria, Vishaldeep; Kumar, Amit; Wolozny, Daniel; Colao, Joe; Jacobson, Elena; Tian, Yuan; O'Meally, Robert N; Krag, Sharon S; Cole, Robert N; Palsson, Bernhard O; Zhang, Hui; Betenbaugh, Michael

    2012-11-01

    To complement the recent genomic sequencing of Chinese hamster ovary (CHO) cells, proteomic analysis was performed on CHO cells including the cellular proteome, secretome, and glycoproteome using tandem mass spectrometry (MS/MS) of multiple fractions obtained from gel electrophoresis, multidimensional liquid chromatography, and solid phase extraction of glycopeptides (SPEG). From the 120 different mass spectrometry analyses generating 682,097 MS/MS spectra, 93,548 unique peptide sequences were identified with at most 0.02 false discovery rate (FDR). A total of 6164 grouped proteins were identified from both glycoproteome and proteome analysis, representing an 8-fold increase in the number of proteins currently identified in the CHO proteome. Furthermore, this is the first proteomic study done using the CHO genome exclusively, which provides for more accurate identification of proteins. From this analysis, the CHO codon frequency was determined and found to be distinct from humans, which will facilitate expression of human proteins in CHO cells. Analysis of the combined proteomic and mRNA data sets indicated the enrichment of a number of pathways including protein processing and apoptosis but depletion of proteins involved in steroid hormone and glycosphingolipid metabolism. Five-hundred four of the detected proteins included N-acetylation modifications, and 1292 different proteins were observed to be N-glycosylated. This first large-scale proteomic analysis will enhance the knowledge base about CHO capabilities for recombinant expression and provide information useful in cell engineering efforts aimed at modifying CHO cellular functions. PMID:22971049

  6. Is Change in Ovary Carbon Status a Cause or a Consequence of Maize Ovary Abortion in Water Deficit during Flowering?

    PubMed

    Oury, Vincent; Caldeira, Cecilio F; Prodhomme, Duyên; Pichon, Jean-Philippe; Gibon, Yves; Tardieu, François; Turc, Olivier

    2016-06-01

    Flower or grain abortion causes large yield losses under water deficit. In maize (Zea mays), it is often attributed to a carbon limitation via the disruption of sucrose cleavage by cell wall invertases in developing ovaries. We have tested this hypothesis versus another linked to the expansive growth of ovaries and silks. We have measured, in silks and ovaries of well-watered or moderately droughted plants, the transcript abundances of genes involved in either tissue expansion or sugar metabolism, together with the concentrations and amounts of sugars, and with the activities of major enzymes of carbon metabolism. Photosynthesis and indicators of sugar export, measured during water deprivation, suggested sugar export maintained by the leaf. The first molecular changes occurred in silks rather than in ovaries and involved genes affecting expansive growth rather than sugar metabolism. Changes in the concentrations and amounts of sugars and in the activities of enzymes of sugar metabolism occurred in apical ovaries that eventually aborted, but probably after the switch to abortion of these ovaries. Hence, we propose that, under moderate water deficits corresponding to most European drought scenarios, changes in carbon metabolism during flowering time are a consequence rather than a cause of the beginning of ovary abortion. A carbon-driven ovary abortion may occur later in the cycle in the case of carbon shortage or under very severe water deficits. These findings support the view that, until the end of silking, expansive growth of reproductive organs is the primary event leading to abortion, rather than a disruption of carbon metabolism. PMID:27208256

  7. Olfactory sensitivity in mammalian species.

    PubMed

    Wackermannová, M; Pinc, L; Jebavý, L

    2016-07-18

    Olfaction enables most mammalian species to detect and discriminate vast numbers of chemical structures called odorants and pheromones. The perception of such chemical compounds is mediated via two major olfactory systems, the main olfactory system and the vomeronasal system, as well as minor systems, such as the septal organ and the Grueneberg ganglion. Distinct differences exist not only among species but also among individuals in terms of their olfactory sensitivity; however, little is known about the mechanisms that determine these differences. In research on the olfactory sensitivity of mammals, scientists thus depend in most cases on behavioral testing. In this article, we reviewed scientific studies performed on various mammalian species using different methodologies and target chemical substances. Human and non-human primates as well as rodents and dogs are the most frequently studied species. Olfactory threshold studies on other species do not exist with the exception of domestic pigs. Olfactory testing performed on seals, elephants, and bats focused more on discriminative abilities than on sensitivity. An overview of olfactory sensitivity studies as well as olfactory detection ability in most studied mammalian species is presented here, focusing on comparable olfactory detection thresholds. The basics of olfactory perception and olfactory sensitivity factors are also described. PMID:27070753

  8. Adiponectin and its receptors in the ovary: further evidence for a link between obesity and hyperandrogenism in polycystic ovary syndrome.

    PubMed

    Comim, Fabio V; Hardy, Kate; Franks, Stephen

    2013-01-01

    Polycystic ovary syndrome (PCOS), characterized by ovarian androgen excess, is the commonest endocrine disorder in women. Obesity increases androgen synthesis, a phenomenon attributed to the accompanying hyperinsulinemia. Our hypothesis was that adipokines, fat cell-derived hormones, play a direct role in modulating ovarian androgen secretion. Therefore, the aims of this study were to explore the effects of adipokines (in particular, adiponectin) on ovarian steroidogenesis and compare the expression of adiponectin receptors in ovaries from women with and without PCO. Sections of archived human ovaries (nine from women with normal ovaries and 16 with PCOS, classified histologically, with reference to menstrual history and ultrasound) were analysed by quantitative morphometry and the proportion of positive-labelling cells compared. In addition, studies of androgen production in relation to adipokine function in primary bovine theca cell culture were also performed. A significantly lower proportion of theca cells expressed adiponectin receptors 1 and 2 (AdipoR1, AdipoR2) in polycystic ovaries than in normal ovaries. In cultured theca cells, adiponectin suppressed androstenedione production and gene expression of LH receptor and key enzymes in the androgen synthesis pathway. Moreover, knockdown of genes for AdipoR1 and AdipoR2 was associated with increased androstenedione secretion by bovine theca cells. These results provide evidence for a direct link between fat cell metabolism and ovarian steroidogenesis, suggesting that disruption of adiponectin and/or its receptors plays a key role in pathogenesis of hyperandrogenism in PCOS. PMID:24260388

  9. Systematic Transfer of Prokaryotic Sensors and Circuits to Mammalian Cells

    PubMed Central

    2015-01-01

    Prokaryotic regulatory proteins respond to diverse signals and represent a rich resource for building synthetic sensors and circuits. The TetR family contains >105 members that use a simple mechanism to respond to stimuli and bind distinct DNA operators. We present a platform that enables the transfer of these regulators to mammalian cells, which is demonstrated using human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells. The repressors are modified to include nuclear localization signals (NLS) and responsive promoters are built by incorporating multiple operators. Activators are also constructed by modifying the protein to include a VP16 domain. Together, this approach yields 15 new regulators that demonstrate 19- to 551-fold induction and retain both the low levels of crosstalk in DNA binding specificity observed between the parent regulators in Escherichia coli, as well as their dynamic range of activity. By taking advantage of the DAPG small molecule sensing mediated by the PhlF repressor, we introduce a new inducible system with 50-fold induction and a threshold of 0.9 μM DAPG, which is comparable to the classic Dox-induced TetR system. A set of NOT gates is constructed from the new repressors and their response function quantified. Finally, the Dox- and DAPG- inducible systems and two new activators are used to build a synthetic enhancer (fuzzy AND gate), requiring the coordination of 5 transcription factors organized into two layers. This work introduces a generic approach for the development of mammalian genetic sensors and circuits to populate a toolbox that can be applied to diverse applications from biomanufacturing to living therapeutics. PMID:25360681

  10. Report of the NASA Mammalian Developmental Biology Working Group

    NASA Technical Reports Server (NTRS)

    Keefe, J. R.

    1985-01-01

    Development is considered to encompass all aspects of the mammalian life span from initial initial germ cell production through the complete life cycle to death of the organism. Thus, gamete production, fertilization, embryogenesis, implantation, fetogenesis, birth, peri- and postnatal maturation, and aging were all considered as stages of a development continuum relevant to problems of Space Biology. Deliberations thus far have been limited to stages of the development cycle from fertilization to early postnatal life. The deliberations are detailed.

  11. Regulation of fibrillins and modulators of TGFβ in fetal bovine and human ovaries.

    PubMed

    Bastian, Nicole A; Bayne, Rosemary A; Hummitzsch, Katja; Hatzirodos, Nicholas; Bonner, Wendy M; Hartanti, Monica D; Irving-Rodgers, Helen F; Anderson, Richard A; Rodgers, Raymond J

    2016-08-01

    Fibrillins 1-3 are stromal extracellular matrix proteins that play important roles in regulating TGFβ activity, which stimulates fibroblasts to proliferate and synthesize collagen. In the developing ovary, the action of stroma is initially necessary for the formation of ovigerous cords and subsequently for the formation of follicles and the surface epithelium of the ovary. FBN3 is highly expressed only in early ovarian development and then it declines. In contrast, FBN1 and 2 are upregulated in later ovarian development. We examined the expression of FBN1-3 in bovine and human fetal ovaries. We used cell dispersion and monolayer culture, cell passaging and tissue culture. Cells were treated with growth factors, hormones or inhibitors to assess the regulation of expression of FBN1-3 When bovine fetal ovarian tissue was cultured, FBN3 expression declined significantly. Treatment with TGFβ-1 increased FBN1 and FBN2 expression in bovine fibroblasts, but did not affect FBN3 expression. Additionally, in cultures of human fetal ovarian fibroblasts (9-17weeks gestational age), the expression of FBN1 and FBN2 increased with passage, whereas FBN3 dramatically decreased. Treatment with activin A and a TGFβ family signaling inhibitor, SB431542, differentially regulated the expression of a range of modulators of TGFβ signaling and of other growth factors in cultured human fetal ovarian fibroblasts suggesting that TGFβ signaling is differentially involved in the regulation of ovarian fibroblasts. Additionally, since the changes in FBN1-3 expression that occur in vitro are those that occur with increasing gestational age in vivo, we suggest that the fetal ovarian fibroblasts mature in vitro. PMID:27222596

  12. Endogenous fluorescence emission of the ovary

    NASA Astrophysics Data System (ADS)

    Utzinger, Urs; Kirkpatrick, Nathaniel D.; Drezek, Rebekah A.; Brewer, Molly A.

    2005-03-01

    Epithelial ovarian cancer has the highest mortality rate among the gynecologic cancers. Early detection would significantly improve survival and quality of life of women at increased risk to develop ovarian cancer. We have constructed a device to investigate endogenous signals of the ovarian tissue surface in the UV C to visible range and describe our initial investigation of the use of optical spectroscopy to characterize the condition of the ovary. We have acquired data from more than 33 patients. A table top spectroscopy system was used to collect endogenous fluorescence with a fiberoptic probe that is compatible with endoscopic techniques. Samples were broken into five groups: Normal-Low Risk (for developing ovarian cancer) Normal-High Risk, Benign, and Cancer. Rigorous statistical analysis was applied to the data using variance tests for direct intensity versus diagnostic group comparisons and principal component analysis (PCA) to study the variance of the whole data set. We conclude that the diagnostically most useful excitation wavelengths are located in the UV. Furthermore, our results indicate that UV B and C are most useful. A safety analysis indicates that UV-C imaging can be conducted at exposure levels below safety thresholds. We found that fluorescence excited in the UV-C and UV-B range increases from benign to normal to cancerous tissues. This is in contrast to the emission created with UV-A excitation which decreased in the same order. We hypothesize that an increase of protein production and a decrease of fluorescence contributions of the extracellular matrix could explain this behavior. Variance analysis also identified fluctuation of fluorescence at 320/380 which is associated with collagen cross link residues. Small differences were observed between the group at high risk and normal risk for ovarian cancer. High risk samples deviated towards the cancer group and low risk samples towards benign group.

  13. Control of mammalian germ cell entry into meiosis.

    PubMed

    Feng, Chun-Wei; Bowles, Josephine; Koopman, Peter

    2014-01-25

    Germ cells are unique in undergoing meiosis to generate oocytes and sperm. In mammals, meiosis onset is before birth in females, or at puberty in males, and recent studies have uncovered several regulatory steps involved in initiating meiosis in each sex. Evidence suggests that retinoic acid (RA) induces expression of the critical pre-meiosis gene Stra8 in germ cells of the fetal ovary, pubertal testis and adult testis. In the fetal testis, CYP26B1 degrades RA, while FGF9 further antagonises RA signalling to suppress meiosis. Failsafe mechanisms involving Nanos2 may further suppress meiosis in the fetal testis. Here, we draw together the growing knowledge relating to these meiotic control mechanisms, and present evidence that they are co-ordinately regulated and that additional factors remain to be identified. Understanding this regulatory network will illuminate not only how the foundations of mammalian reproduction are laid, but also how mis-regulation of these steps can result in infertility or germline tumours. PMID:24076097

  14. Rarity in conspicuity—Ultrasound diagnosis of sliding left inguinal hernia through canal of Nuck with uterus, fallopian tubes and ovaries

    PubMed Central

    Muthiyal, Sreekumar; Kini, Vishwanatha; Kounsal, Avin; Ibrahim, Ashraf Abdelhamid

    2016-01-01

    We present a case of a one month old female infant who presented with left inguinal swelling. She was prematurely born at 32 weeks of gestational age. Preoperative ultrasound showed features of sliding indirect inguinal hernia with both ovaries, fallopian tubes and uterus; which were also evident per operatively. Patient underwent successful hernia repair and uneventful post-operative period. Patient is on follow up currently. In conclusion, we attempt to highlight the exiguous prevalence of inguinal hernia with uterus, fallopian tubes and ovaries; which has been sparsely reported in the literature and also the importance of preoperative of sonography. PMID:27069977

  15. Cross-species correlation between queen mating numbers and worker ovary sizes suggests kin conflict may influence ovary size evolution in honeybees

    NASA Astrophysics Data System (ADS)

    Rueppell, Olav; Phaincharoen, Mananya; Kuster, Ryan; Tingek, Salim

    2011-09-01

    During social evolution, the ovary size of reproductively specialized honey bee queens has dramatically increased while their workers have evolved much smaller ovaries. However, worker division of labor and reproductive competition under queenless conditions are influenced by worker ovary size. Little comparative information on ovary size exists in the different honey bee species. Here, we report ovariole numbers of freshly dissected workers from six Apis species from two locations in Southeast Asia. The average number of worker ovarioles differs significantly among species. It is strongly correlated with the average mating number of queens, irrespective of body size. Apis dorsata, in particular, is characterized by numerous matings and very large worker ovaries. The relation between queen mating number and ovary size across the six species suggests that individual selection via reproductive competition plays a role in worker ovary size evolution. This indicates that genetic diversity, generated by multiple mating, may bear a fitness cost at the colony level.

  16. Dehydroepiandrosterone-induced polycystic ovaries and acyclicity in the rat.

    PubMed

    Knudsen, J F; Costoff, A; Mahesh, V B

    1975-08-01

    Administration of dehydroepiandrosterone (DHA) to the immature female rat resulted in one precocious ovulation followed by ovulatory failure. The animals exhibited either "constant-estrus" or "constant-diestrus" vaginal smears, and the ovaries were either polycystic or contained corpus luteum-like structures. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels showed an ovulatory type surge on day 30, at the time of the precocious ovulation. Thereafter, serum FSH levels were comparable to those of control rats, whereas the LH levels were very low. Serum prolactin was elevated significantly in DHA-treated animals. The ovaries of DHA-treated animals were responsive to gonadotropins and the pituitary was responsive to luteinizing hormone-releasing hormone. Withdrawal of androgen treatment resulted in restoration of cyclicity. This animal model demonstrates that an androgen insult can cause ovulatory failure and polycystic ovaries in spite of normal ovaries, adrenals, and hypothalamic-pituitary mechanisms. That such ovulatory failure is a result of the androgen administration is further substantiated by restoration of cyclicity after androgen withdrawal. This animal model in several ways is similar to the human polycystic ovary syndrome and has a potential application in the study of the mechanism of androgen-induced ovulatory failure. PMID:125663

  17. Human umbilical cord mesenchymal stem cell transplantation restores damaged ovaries

    PubMed Central

    Zhu, Shao-Fang; Hu, Hong-Bo; Xu, Hong-Yan; Fu, Xia-Fei; Peng, Dong-Xian; Su, Wei-Yan; He, Yuan-Li

    2015-01-01

    Ovarian injury because of chemotherapy can decrease the levels of sexual hormones and potentia generandi of patients, thereby greatly reducing quality of life. The goal of this study was to investigate which transplantation method for human umbilical cord mesenchymal stem cells (HUMSCs) can recover ovarian function that has been damaged by chemotherapy. A rat model of ovarian injury was established using an intraperitoneal injection of cyclophosphamide. Membrane-labelled HUMSCs were subsequently injected directly into ovary tissue or tail vein. The distribution of fluorescently labelled HUMSCs, estrous cycle, sexual hormone levels, and potentia generandi of treated and control rats were then examined. HUMSCs injected into the ovary only distributed to the ovary and uterus, while HUMSCs injected via tail vein were detected in the ovary, uterus, kidney, liver and lung. The estrous cycle, levels of sex hormones and potentia generandi of the treated rats were also recovered to a certain degree. Moreover, in some transplanted rats, fertility was restored and their offspring developed normally. While ovary injection could recover ovarian function faster, both methods produced similar results in the later stages of observation. Therefore, our results suggest that transplantation of HUMSCs by tail vein injection represents a minimally invasive and effective treatment method for ovarian injury. PMID:25922900

  18. Bmovo-1 Regulates Ovary Size in the Silkworm, Bombyx mori

    PubMed Central

    Cao, Guangli; Huang, Moli; Xue, Gaoxu; Qian, Ying; Song, Zuowei; Gong, Chengliang

    2014-01-01

    The regulation of antagonistic OVO isoforms is critical for germline formation and differentiation in Drosophila. However, little is known about genes related to ovary development. In this study, we cloned the Bombyx mori ovo gene and investigated its four alternatively spliced isoforms. BmOVO-1, BmOVO-2 and BmOVO-3 all had four C2H2 type zinc fingers, but differed at the N-terminal ends, while BmOVO-4 had a single zinc finger. Bmovo-1, Bmovo-2 and Bmovo-4 showed the highest levels of mRNA in ovaries, while Bmovo-3 was primarily expressed in testes. The mRNA expression pattern suggested that Bmovo expression was related to ovary development. RNAi and transgenic techniques were used to analyze the biological function of Bmovo. The results showed that when the Bmovo gene was downregulated, oviposition number decreased. Upregulation of Bmovo-1 in the gonads of transgenic silkworms increased oviposition number and elevated the trehalose contents of hemolymph and ovaries. We concluded that Bmovo-1 was involved in protein synthesis, contributing to the development of ovaries and oviposition number in silkworms. PMID:25119438

  19. Evolutionary paths to mammalian cochleae.

    PubMed

    Manley, Geoffrey A

    2012-12-01

    Evolution of the cochlea and high-frequency hearing (>20 kHz; ultrasonic to humans) in mammals has been a subject of research for many years. Recent advances in paleontological techniques, especially the use of micro-CT scans, now provide important new insights that are here reviewed. True mammals arose more than 200 million years (Ma) ago. Of these, three lineages survived into recent geological times. These animals uniquely developed three middle ear ossicles, but these ossicles were not initially freely suspended as in modern mammals. The earliest mammalian cochleae were only about 2 mm long and contained a lagena macula. In the multituberculate and monotreme mammalian lineages, the cochlea remained relatively short and did not coil, even in modern representatives. In the lineage leading to modern therians (placental and marsupial mammals), cochlear coiling did develop, but only after a period of at least 60 Ma. Even Late Jurassic mammals show only a 270 ° cochlear coil and a cochlear canal length of merely 3 mm. Comparisons of modern organisms, mammalian ancestors, and the state of the middle ear strongly suggest that high-frequency hearing (>20 kHz) was not realized until the early Cretaceous (~125 Ma). At that time, therian mammals arose and possessed a fully coiled cochlea. The evolution of modern features of the middle ear and cochlea in the many later lineages of therians was, however, a mosaic and different features arose at different times. In parallel with cochlear structural evolution, prestins in therian mammals evolved into effective components of a new motor system. Ultrasonic hearing developed quite late-the earliest bat cochleae (~60 Ma) did not show features characteristic of those of modern bats that are sensitive to high ultrasonic frequencies. PMID:22983571

  20. Outcome of Ovarian Drilling in Women with Polycystic Ovary Syndrome

    PubMed Central

    Gundabattula, Sirisha Rao

    2015-01-01

    Objective: To determine the effectiveness and safety of laparoscopic ovarian drilling (LOD) in inducing ovulation in women with polycystic ovary syndrome (PCOS) who failed to conceive after medical methods of ovulation induction. Materials and Methods: A retrospective study of all women who underwent LOD as a treatment for anovulatory infertility between January 2010 and December 2011 was conducted. Women diagnosed to have PCOS by the Rotterdam criteria were considered for the study. Those who had PCOS but were associated with male factor infertility, deep infiltrating endometriosis and submucous fibroids were excluded. Results: A total of 43 women underwent LOD during the study period. Majority were aged 26 to 30 years and two-thirds were overweight or obese. Most (72%) of them had primary infertility. Other factors which could have contributed to infertility such as superficial endometriosis, septate uterus and unilateral tubal block were observed in 30.2% of the women, which were dealt with concomitantly. When we excluded the 14% who were lost to follow up, 23 of 43 (53.5%) women achieved pregnancy and almost 70% of them did so within the first 6 months. None of our study population had ovarian hyperstimulation or multiple pregnancy. Conclusion: LOD thus not only helps in regulating ovulation and enhancing conception rates but also provides an opportunity to assess the pelvis for other potential causes of subfertility which could be treated at the same time. We therefore believe that diagnostic hysteroscopy and laparoscopy should be offered quite high-up in the hierarchy of infertility investigations and treatment. PMID:25859492

  1. The Diagnosis of Polycystic Ovary Syndrome in Adolescents.

    PubMed

    Rosenfield, Robert L

    2015-12-01

    Consensus has recently been reached by international pediatric subspecialty societies that otherwise unexplained persistent hyperandrogenic anovulation using age- and stage-appropriate standards are appropriate diagnostic criteria for polycystic ovary syndrome (PCOS) in adolescents. The purpose of this review is to summarize these recommendations and discuss their basis and implications. Anovulation is indicated by abnormal uterine bleeding, which exists when menstrual cycle length is outside the normal range or bleeding is excessive: cycles outside 19 to 90 days are always abnormal, and most are 21 to 45 days even during the first postmenarcheal year. Continued menstrual abnormality in a hyperandrogenic adolescent for 1 year prognosticates at least 50% risk of persistence. Hyperandrogenism is best indicated by persistent elevation of serum testosterone above adult norms as determined in a reliable reference laboratory. Because hyperandrogenemia documentation can be problematic, moderate-severe hirsutism constitutes clinical evidence of hyperandrogenism. Moderate-severe inflammatory acne vulgaris unresponsive to topical treatment is an indication to test for hyperandrogenemia. Treatment of PCOS is symptom-directed. Cyclic estrogen-progestin oral contraceptives are ordinarily the preferred first-line medical treatment because they reliably improve both the menstrual abnormality and hyperandrogenism. First-line treatment of the comorbidities of obesity and insulin resistance is lifestyle modification with calorie restriction and increased exercise. Metformin in conjunction with behavior modification is indicated for glucose intolerance. Although persistence of hyperandrogenic anovulation for ≥2 years ensures the distinction of PCOS from physiologic anovulation, early workup is advisable to make a provisional diagnosis so that combined oral contraceptive treatment, which will mask diagnosis by suppressing hyperandrogenemia, is not unnecessarily delayed. PMID

  2. Idiopathic intracranial hypertension, polycystic-ovary syndrome, and thrombophilia.

    PubMed

    Glueck, Charles J; Aregawi, Dawit; Goldenberg, Naila; Golnik, Karl C; Sieve, Luann; Wang, Ping

    2005-02-01

    We studied thrombophilia, hypofibrinolysis, and polycystic-ovary syndrome (PCOS) in 65 women consecutively referred because of idiopathic intracranial hypertension (IIH) as a means of better understanding the origin of IIH, with the ultimate goal of developing novel medical therapies for IIH. Our hypothesis: IIH results in part from inadequate drainage of cerebrospinal fluid (CSF) resulting from thrombotic obstruction to CSF resorption-outflow, favored by thrombophilia-hypofibrinolysis. We conducted the polymerase chain reaction (PCR) and assessed serologic coagulation measures in 65 women (64 of them white) with IIH, PCR in 102 healthy white female controls (72 children, 30 age-matched adults), and serologic measures in the 30 adults. Of the 65 patients, 37 (57%) were found to have PCOS; 16 (43%) were obese (BMI > or = 30 to < 40), and 19 (51%) were extremely obese (BMI > or = 40). Of the 65 women with IIH, 25 (38%) were homozygous for the thrombophilic C677T MTHFR mutation, compared with 14% of controls (14/102) ( P = .0002). Thrombophilic high concentrations of factor VIII (>150%) were present in 9 of 65 (14%) IIH cases, compared with 0 of 30 controls (0%) (Fisher's p [p f ] = .053). An increased concentration of lipoprotein A (> or = 35 mg/dL), associated with hypofibrinolysis, was present in 19 of 65 IIH cases (29%), compared with 3 of 30 controls (10%) (p f = .039). IIH occurred in 18 of 65 IIH patients taking estrogen-progestin contraceptives (28%), in 6 patients taking hormone-replacement therapy (9%), and in 5 pregnant subjects (8%). We speculate that PCOS, associated with obesity and extreme obesity, is a treatable promoter of IIH. We also speculate that if thrombophilia-hypofibrinolysis and subsequent thrombosis are associated with reduced CSF resorption in the arachnoid villi of the brain, thrombophilia and hypofibrinolysis-often exacerbated by thrombophilic exogenous estrogens, pregnancy, or the paradoxical hyperestrogenemia of PCOS-are treatable

  3. FOXO3a is involved in the apoptosis of naked oocytes and oocytes of primordial follicles from neonatal rat ovaries.

    PubMed

    Liu, Hong; Luo, Li-Li; Qian, Yuan-Shu; Fu, Yu-Cai; Sui, Xu-Xia; Geng, Yi-Jie; Huang, Da-Na; Gao, Shi-Tong; Zhang, Ren-Li

    2009-04-17

    Inhibition of the forkhead transcription factor, FOXO3a, can promote the transition from primordial to primary follicle and subsequent follicle development in mammalian ovaries. Stem cell factor (SCF) initiates anti-apoptotic signaling from its membrane receptor, c-kit, to Bcl-2 family members through PI3K/AKT in oocytes of primordial follicles. However, whether FOXO3a mediates the apoptosis of naked oocytes and oocytes of primordial follicles remains unknown. In the present study, oocytes from nests and primordial follicles from neonatal rat ovaries were cultured, and oocyte apoptosis was examined using the TUNEL technique. The pro-apoptotic action of FOXO3a and the potential signal transduction pathways were investigated using RT-PCR, Western blot, and immunocytochemistry. Culturing oocytes in the presence of SCF did not affect the level of total FOXO3a protein, but rapidly elevated the level of phosphorylated FOXO3a (indicating functional suppression). As phosphorylated FOXO3a increased, oocyte apoptosis was inhibited. The specific PI3K/Akt inhibitor, LY 294002, abolished the phosphorylation of FOXO3a and the anti-apoptotic action of SCF. SCF down-regulated the expression of p27KIP1 and pro-apoptotic factors such as Bim, Bad, and Bax, and this activity was reversed by LY 294002. SCF up-regulated the expression of MnSOD, which was also inhibited by LY 294002. However, SCF had no effect on Bcl-2 protein. These results suggest that FOXO3a is involved in oocyte apoptosis in the neonatal rat ovary, and the SCF-PI3K/Akt-FOXO3a signaling pathway mediates oocyte apoptosis and primordial follicle formation. PMID:19258007

  4. Sertoliform Endometrioid Tumor of Ovary Presenting as Torsion

    PubMed Central

    Pai, Prathiksha; Jadhav, Meena N; Patil, Rashmi K; Kittur, Shreekant K

    2016-01-01

    Sertoliform endometrioid carcinoma of the ovary (SEC) is an uncommon variant that bears histologic similarity to sertoli and sertoli-leydig cell tumors. We report an interesting case of SEC in a 55-year-old female with a left ovarian mass with torsion. Histology revealed an SEC, featuring foci of typical endometrioid carcinoma, and areas composed of uniform, small, hollow tubules lined by columnar cells with apical cytoplasm. Tumor cells were strongly immunoreactive for EMA and cytokeratin but negative for inhibin; thus, confirming the diagnosis of SEC ovary. Recognition of this tumor is important as it is a well-differentiated, low-grade malignancy that displays good prognosis when confined to the ovary. PMID:27365921

  5. Sertoliform Endometrioid Tumor of Ovary Presenting as Torsion.

    PubMed

    Pai, Prathiksha; Jadhav, Meena N; Patil, Rashmi K; Kittur, Shreekant K

    2016-01-01

    Sertoliform endometrioid carcinoma of the ovary (SEC) is an uncommon variant that bears histologic similarity to sertoli and sertoli-leydig cell tumors. We report an interesting case of SEC in a 55-year-old female with a left ovarian mass with torsion. Histology revealed an SEC, featuring foci of typical endometrioid carcinoma, and areas composed of uniform, small, hollow tubules lined by columnar cells with apical cytoplasm. Tumor cells were strongly immunoreactive for EMA and cytokeratin but negative for inhibin; thus, confirming the diagnosis of SEC ovary. Recognition of this tumor is important as it is a well-differentiated, low-grade malignancy that displays good prognosis when confined to the ovary. PMID:27365921

  6. [Mature cystic teratoma of the ovary with a small ganglioneuroma].

    PubMed

    Marucci, G; Collina, G

    2006-02-01

    A case of ganglioneuroma arising within a cystic mature teratoma of the ovary in a 34-year-old woman is reported. Patient underwent right adnexectomy. The ovary was completely replaced by a bilocular cystic lesion, measuring 8 cm in diameter and filled with adipose tissue and pilosebaceous material. Microscopically the cyst was composed by a mature cystic teratoma containing skin with dermal appendages, fatty tissue and bronchial epithelium. Furthermore a nodule (0.5 cm in size) composed of mature ganglion cells, axons and Schwann cells, was identified. Ganglion cells were positive for NSE and synaptophysin, while Schwann cells stained positively with S100 protein and GFAP. To the best of our knowledgment this is the first reported cases of ganglioneuroma arisen within a cystic mature teratoma of the ovary. PMID:16789685

  7. IMAC capture of recombinant protein from unclarified mammalian cell feed streams

    PubMed Central

    Kinna, Alexander; Tolner, Berend; Rota, Enrique Miranda; Titchener‐Hooker, Nigel; Nesbeth, Darren

    2015-01-01

    ABSTRACT Fusion‐tag affinity chromatography is a key technique in recombinant protein purification. Current methods for protein recovery from mammalian cells are hampered by the need for feed stream clarification. We have developed a method for direct capture using immobilized metal affinity chromatography (IMAC) of hexahistidine (His6) tagged proteins from unclarified mammalian cell feed streams. The process employs radial flow chromatography with 300–500 μm diameter agarose resin beads that allow free passage of cells but capture His‐tagged proteins from the feed stream; circumventing expensive and cumbersome centrifugation and/or filtration steps. The method is exemplified by Chinese Hamster Ovary (CHO) cell expression and subsequent recovery of recombinant His‐tagged carcinoembryonic antigen (CEA); a heavily glycosylated and clinically relevant protein. Despite operating at a high NaCl concentration necessary for IMAC binding, cells remained over 96% viable after passage through the column with host cell proteases and DNA detected at ∼8 U/mL and 2 ng/μL in column flow‐through, respectively. Recovery of His‐tagged CEA from unclarified feed yielded 71% product recovery. This work provides a basis for direct primary capture of fully glycosylated recombinant proteins from unclarified mammalian cell feed streams. Biotechnol. Bioeng. 2016;113: 130–140. © 2015 Wiley Periodicals, Inc. PMID:26174988

  8. DNA modifications in the mammalian brain

    PubMed Central

    Shin, Jaehoon; Ming, Guo-li; Song, Hongjun

    2014-01-01

    DNA methylation is a crucial epigenetic mark in mammalian development, genomic imprinting, X-inactivation, chromosomal stability and suppressing parasitic DNA elements. DNA methylation in neurons has also been suggested to play important roles for mammalian neuronal functions, and learning and memory. In this review, we first summarize recent discoveries and fundamental principles of DNA modifications in the general epigenetics field. We then describe the profiles of different DNA modifications in the mammalian brain genome. Finally, we discuss roles of DNA modifications in mammalian brain development and function. PMID:25135973

  9. [A Case of Carcinoma of the Uterine Body, Right Ovary, and Duodenum in a Patient with Familial Adenomatous Polyposis].

    PubMed

    Ishibashi, Keiichiro; Watanabe, Yuichiro; Chika, Noriyasu; Tajima, Yusuke; Suzuki, Okihide; Matsuzawa, Takeaki; Kumamoto, Kensuke; Fukuchi, Minoru; Kumagai, Yoichi; Baba, Hiroyuki; Mochiki, Erito; Iwama, Takeo; Ishida, Hideyuki

    2015-11-01

    We report a case of 4 carcinomas of the uterine body, right ovary, and duodenum in a patient with familial adenomatous polyposis (FAP). Her mother's family line carries FAP. She underwent proctocolectomy with ileoanal anastomosis for FAP when she was 20 years old. She was diagnosed with carcinoma of the uterine body and right ovary, and underwent abdominal total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy at 48 years of age. The pathological examination revealed endometrioid adenocarcinoma of the uterine body (Stage ⅠB) and endometrioid adenocarcinoma of the right ovary (Stage ⅠA). Her diagnosis was Stage Ⅳ according to the Spigelman classification of duodenal polyposis, and she underwent pancreas-preserving total duodenectomy at 50 years of age. The pathological examination was conclusive for 2 carcinomas in the adenoma, which were 20 mm and 25 mm in diameter, respectively. She has been well without any evidence of cancer recurrence 20 months after the pancreas-preserving total duodenectomy. PMID:26805148

  10. ALTERED STEROIDOGENESIS IN WHOLE-OVARY AND ADRENAL CULTURE IN CYCLING RATS

    EPA Science Inventory

    Cultures of minced, whole-ovary (whole-ovary culture) were used to determine if three selected chemicals altered steroidogenic profiles. irst, phenolaulfonthalein (PST), when used in culture medium, was tested for its influence on in vitro steroidogenesis. ext, aminoglutethimide ...