Department of Reproductive Health and Research including the UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP) WHO/RHR12.12 Annual Technical Report 2011 Department of Reproductive Health and Research including the UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP) Annual Technical Report, 2011 WHO/RHR/12.12 © World Health Organization 2012 All rights reserved. Publications of the World Health Organization are available on the WHO web site (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: bookorders@who.int). 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Contribution to WHO’s Medium-Term Strategic Plan 1 Universal access to sexual and reproductive health in the context of the primary health care approach 3 Promoting family planning 11 Improving maternal and perinatal health 19 Preventing unsafe abortion 27 Controlling sexually transmitted and reproductive tract infections 35 Gender, reproductive rights, sexual health and adolescence 41 Research capacity strengthening and programme development 53 Knowledge exchange and transfer 67 Policy and programmatic issues 71 Monitoring and evaluation 75 Health-systems research 81 Implementing Best Practices Initiative 85 Reproductive health essential medicines 89 CROSS-CUTTING AREAS WITHIN INTER-TEAM WORKING GROUPS Knowledge Synthesis and Exchange & Implementation Research 93 Innovations to improve sexual and reproductive health 99 Linkages between sexual and reproductive health and HIV/AIDS interventions 113 Men and sexual and Hormonal Control of Human Reproduction Hormonal Control of Human Reproduction Bởi: OpenStaxCollege The human male and female reproductive cycles are controlled by the interaction of hormones from the hypothalamus and anterior pituitary with hormones from reproductive tissues and organs In both sexes, the hypothalamus monitors and causes the release of hormones from the pituitary gland When the reproductive hormone is required, the hypothalamus sends a gonadotropin-releasing hormone (GnRH) to the anterior pituitary This causes the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary into the blood Note that the body must reach puberty in order for the adrenals to release the hormones that must be present for GnRH to be produced Although FSH and LH are named after their functions in female reproduction, they are produced in both sexes and play important roles in controlling reproduction Other hormones have specific functions in the male and female reproductive systems Male Hormones At the onset of puberty, the hypothalamus causes the release of FSH and LH into the male system for the first time FSH enters the testes and stimulates the Sertoli cells to begin facilitating spermatogenesis using negative feedback, as illustrated in [link] LH also enters the testes and stimulates the interstitial cells of Leydig to make and release testosterone into the testes and the blood Testosterone, the hormone responsible for the secondary sexual characteristics that develop in the male during adolescence, stimulates spermatogenesis These secondary sex characteristics include a deepening of the voice, the growth of facial, axillary, and pubic hair, and the beginnings of the sex drive 1/9 Hormonal Control of Human Reproduction Hormones control sperm production in a negative feedback system A negative feedback system occurs in the male with rising levels of testosterone acting on the hypothalamus and anterior pituitary to inhibit the release of GnRH, FSH, and LH The Sertoli cells produce the hormone inhibin, which is released into the blood when the sperm count is too high This inhibits the release of GnRH and FSH, which will cause spermatogenesis to slow down If the sperm count reaches 20 million/ml, the Sertoli cells cease the release of inhibin, and the sperm count increases Female Hormones The control of reproduction in females is more complex As with the male, the anterior pituitary hormones cause the release of the hormones FSH and LH In addition, estrogens and progesterone are released from the developing follicles Estrogen is the reproductive hormone in females that assists in endometrial regrowth, ovulation, and calcium absorption; it is also responsible for the secondary sexual characteristics of females These include breast development, flaring of the hips, and a shorter period necessary for bone maturation Progesterone assists in endometrial re-growth and inhibition of FSH and LH release In females, FSH stimulates development of egg cells, called ova, which develop in structures called follicles Follicle cells produce the hormone inhibin, which inhibits FSH production LH also plays a role in the development of ova, induction of ovulation, and stimulation of estradiol and progesterone production by the ovaries Estradiol and progesterone are steroid hormones that prepare the body for pregnancy Estradiol produces secondary sex characteristics in females, while both estradiol and progesterone regulate the menstrual cycle 2/9 Hormonal Control of Human Reproduction The Ovarian Cycle and the Menstrual Cycle The ovarian cycle governs the preparation of endocrine tissues and release of eggs, while the menstrual cycle governs the preparation and maintenance of the uterine lining These cycles occur concurrently and are coordinated over a 22–32 day cycle, with an average length of 28 days The first half of the ovarian cycle is the follicular phase shown in [link] Slowly rising levels of FSH and LH cause the growth of follicles on the surface of the ovary This process prepares the egg for ovulation As the follicles grow, they begin releasing estrogens and a low level of progesterone Progesterone maintains the endometrium to help ensure pregnancy The trip through the fallopian tube takes about seven days At this stage of development, called the morula, there are 30-60 cells If pregnancy implantation does not occur, the lining is sloughed off After about five days, estrogen levels rise and the menstrual cycle enters the proliferative phase The endometrium begins to regrow, replacing the blood vessels and glands that deteriorated during the end of the last cycle Art Connection 3/9 Hormonal Control of Human Reproduction The ovarian and menstrual cycles of female reproduction are regulated by hormones produced by the hypothalamus, pituitary, and ovaries Which of the following statements about hormone regulation of the female reproductive cycle is false? LH and FSH are produced in the ...RESEARCH ARTICLE Open Access The European Society of Human Reproduction and Embryology guideline for the diagnosis and treatment of endometriosis: an electronic guideline implementability appraisal Lotte JEW van Dijk 1 , Willianne LDM Nelen 1* , Thomas M D’Hooghe 2 , Gerard AJ Dunselman 3 , Rosella PMG Hermens 4 , Christina Bergh 5 , Karl G Nygren 6 , Arnold HM Simons 7 , Petra de Sutter 8 , Catherine Marshall 9 , Jako S Burgers 4 , Jan AM Kremer 1 Abstract Background: Clinical guidelines are intended to improve healthcare. However, even if guidelines are excellent, their implementation is not assured. In subfertility care, the European Society of Human Reproduction and Embryology (ESHRE) guidelines have been inventoried, and their methodological quality has been assessed. To improve the impact of the ESHRE guidelines and to improve European subfertility care, it is important to optimise the implementability of guidelines. We therefore investigated the implementation barriers of the ESHRE guideline with the best methodological quality and evaluated the used instrument for usability and feasibility. Methods: We reviewed the ESHRE guideline for the diagnosis and treatment of endometriosis to assess its implementability. We used an electronic version of the guideline implementability appraisal (eGLIA) instrument. This eGLIA tool consists of 31 questions grouped into 10 dimensions. Seven items address the guideline as a whole, and 24 items assess the individual recommendations in the guideline. The eGLIA instrument identifies factors that influence the implementability of the guideline recommendations. These factors can be divided into facilitators that promote implementation and barriers that oppose implementation. A panel of 10 experts from three European countries appraised all 36 recommendations of the guideline. They discussed discrepancies in a teleconference and completed a questionnaire to evaluate the ease of use and overall utility of the eGLIA instrument. Results: Two of the 36 guideline recommendations were straightforward to implement. Five recommendations were considered simply statements because they contained no actions. The remaining 29 recommendations were implementable with some adjustments. We found facilitators of the guideline implementability in the quality of decidability, presentation and formatting, apparent validity, and novelty or innovation of the recommendations. Vaguely defined actions, lack of facilities, immeasurable outcomes, and inflexibility within the recommendations formed barriers to implementation. The eGLIA instrument was generally useful and easy to use. However, assessment with the eGLIA instrument is very time-consuming. Conclusions: The ESHRE guideline for the diagnosis and treatment of endometriosis could be improved to facilitate its implementation in daily practice. Th e eGLIA instrument is a helpful tool for identifying obstacles to implementation of a guideline. However, we recommend a concise version of this instrument. * Correspondence: w.nelen@obgyn.umcn.nl 1 Department of Obstetrics & Gynaecology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands Full list of author information is available at the end of the article van Dijk et al. Implementation Science 2011, 6:7 http://www.implementationscience.com/content/6/1/7 Implementation Science © 2011 van Dijk et al; licensee BioMed Ce ntral Ltd. Thi s is an Open Ac cess article distributed under the terms of the Creativ e Commons Attribution License (http://creativecommons.o rg/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background Clinical guidelines are important tools for improving the quality, effectiveness, and appropriateness of healthcare [1-5]. They are intende d to bridge the gap b etween research and practice and to assist clinicians and patients in clinical decision making [2,6,7]. Moreover, they can DISSECTING THE HORMONAL CONTROL OF THE SALT STRESS RESPONSE IN ARABIDOPSIS ROOTS YU GENG A THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF BIOLOGICAL SCIENCES NATIONAL UNIVERSITY OF SINGAPORE 2013 ACKNOWLEDGEMENT ACKNOWLEDGEMENT First I would like to thank my supervisor José R. Dinneny. He is the one who gave me the opportunity to start this amazing journey. He is also the one giving me lots of help and support in the past four years. He makes me became a better scientist. I appreciate Department of Biological Science in National University of Singapore for allowing me to be a part of the top university in Asia. I appreciate Temasek Life Sciences Laboratory and Carnegie Institution for Science for their generous financial support. There is no way I can finish my Ph D training without them. I would like to thank all the members in Dinneny’s lab for the discussions and help. I am very lucky to work with these people. I would like to thank people from Yu Hao’s lab in TLL, people from Wang Zhiyong’s lab in Carnegie, David Ehrhardt and Heather Cartwright for their valuable advice and help. Finally, I would like to thank my family and friends for them to understand me, stand by me no matter what decision I made. Aug 2013 Geng Yu i TABLE OF CONTENTS TABLE OF CONTENTS ACKNOWLEGEMENT i TABLE OF CONTENTS ii SUMMARY . vii LIST OF TABLES . ix LIST OF FIGURES x LIST OF ABBREVIATIONS AND SYMBOLS . xiii Chapter LITERATURE REVIEW . 1.1 Introduction . 1.2 Salt stress in plants . 1.2.1 Early effects . 1.2.2 Long term effects . 1.3 Salt stress signaling in plants . 1.3.1 CBL-CIPK signaling network .7 1.3.1.1 Salt Overly Sensitive (SOS) pathway 1.3.1.2 CBL1/CBL9-CIPK23-AKT1 network and K+ transportation .9 1.3.2 Osmotic stress signaling .10 1.3.3 The transcriptional programs and phyto-hormones in salt stress response .11 1.3.3.1 ABA biosynthesis and signaling pathways, and its function in salt stress…………………………………………………………………………… .11 ii TABLE OF CONTENTS 1.3.3.2 Jasmonates ( JAs) biosynthesis and signaling pathway and its function in salt stress 16 1.3.3.3 Ethylene (ET) biosynthesis and signaling pathway and its function in salt stress .18 1.3.3.4 Gibberellic acid (GA) and Brassinosteriod (BR), two positive growth regulators and their functions in salt stress 20 1.4 Arabidopsis root development .23 1.5 Cell type specific studies in Arabidopsis roots 25 1.6 Objective and significance of this study 28 Chapter MATERIAL AND METHODS .31 2.1 Plant materials .32 2.2 Plant growth conditions 32 2.3 Live-imaging and data analysis .33 2.4 Sample preparation, RNA isolation, microarray hybridization and data analysis: Agilent array 33 2.4.1 Protoplasting of roots and isolation of GFP-enriched cell populations by FACS Chapter RESULTS AND DISCUSSION 87 4.1 Abstract High salinity is an important agricultural contaminant that causes damage to the plant. However, the distinctive roles of different cell types in the transition process from normal growth to stress acclimation are largely unknown. Here, we show that ethylene promotes radial expansion of cortex cells through the canonical ethylene signaling pathway, while its precursor ACC may have an ethylene-independent function of inhibiting cell elongation during salt stress. By using mutants that have radial patterning defects, we show that salt-mediated induction of ethylene biosynthetic pathway members at the transcriptional level depends on the endodermis. In order to find the components that work downstream of ethylene in regulating salt-mediated cell swelling, we performed microarray experiments with ethylene signaling mutants at early stages of salt stress. Bioinformatic analysis revealed cell-type specificity in the expression pattern of the downstream targets of ethylene during salt stress, indicating the cell-type specific function of ethylene in regulating the salt response. Further, we demonstrated that local synthesis of auxin in the early elongation zone serves as a downstream component of ethylene signaling during salt stress. Based on these observations, we that ethylene promotes salt-mediated cortical cell swelling through auxin signaling in an endodermisdependent manner. 88 4.2 Introduction Plants, through intricate compositions of cell and tissue types, are good planners. In favorable habitats, they plan their lives in a simple and effective way. However, when they are facing stressful environments, they need to quickly coordinate their different tissue layers, conduct complex regulation to change their developmental and physiological plane to adapt to such environments. Salt stress is one of the most common environmental stresses. It creates both osmotic and ionic stress to affect plant growth. Decades of research into the effects of salinity on plant physiology and development have generated a wealth of information. However, the distinctive roles of different cell types in the transition process from normal growth to stress adaptation are largely unknown. In this study, we used a particular salt-sensitive plant, Arabidopsis thaliana, focusing on one environmental stress, high salinity, in order to understand how plants make this transition and how different cell types contribute to this process. High salinity has complex effects on root physiology. These effects are mainly caused by both osmotic stress and ionic stress. When the rhizosphere soil is contaminated with toxic soluble molecules, like NaCl, the water potential of the soil become lower, making it more difficult for plants to take up water from the environment. When the cells are suffering from dehydration, the turgor pressure of the cells against their cell walls is reduced, which can reduce the rigidity of plants and make them more vulnerable to wounding. Along with water deprivation becoming more and more severe, many biological processes, such as photosynthesis, are disrupted (Allen et al., 2001). 89 Furthermore, due to their similar chemical properties, the high amount of Na+ will break the K+/Na+ balance, leading to K+ deprivation by engrossing ion channels, which are normally used to transport K+ into the cell (Rubio et al., 1995). It has been shown that K+ is crucial for the activity of many enzymes; lack of K+ will largely affect plant development and growth (Shabala et al., 2008). When exposed to salt stress, the Arabidopsis root undergoes dramatic morphological changes, which include the inhibition of primary root elongation, reduction of meristem size, and inhibition of lateral root formation in a dosage-dependent manner (Burssens et al., 2000; West et al., 2004; Wang et al., 2009). Besides Int. J. Med. Sci. 2007, 4 131International Journal of Medical Sciences ISSN 1449-1907 www.medsci.org 2007 4(3):131-139 © Ivyspring International Publisher. All rights reserved Research Paper Thioglycosides as inhibitors of hSGLT1 and hSGLT2: Potential therapeutic agents for the control of hyperglycemia in diabetes Francisco Castaneda1, Antje Burse2, Wilhelm Boland2, Rolf K-H. Kinne1 1. Laboratory for Molecular Pathobiochemistry and Clinical Research, Max Planck Institute of Molecular Physiology, Dort-mund, Germany; 2. Max Planck Institute for Chemical Ecology, Dortmund, Germany Correspondence to: Francisco Castaneda, MD, Laboratory for Molecular Pathobiochemistry and Clinical Research, Max Planck Institute for Molecular Physiology, Otto-Hahn-Str. 11, 44227 Dortmund, Germany; Tel. 49-231-9742-6490, Fax. 49-231-133-2699, E-mail: francisco.castaneda@mpi-dortmund.mpg.de Received: 2007.04.14; Accepted: 2007.04.30; Published: 2007.05.05 The treatment of diabetes has been mainly focused on maintaining normal blood glucose concentrations. Insulin and hypoglycemic agents have been used as standard therapeutic strategies. However, these are characterized by limited efficacy and adverse side effects, making the development of new therapeutic alternatives mandatory. Inhibition of glucose reabsorption in the kidney, mediated by SGLT1 or SGLT2, represents a promising thera-peutic approach. Therefore, the aim of the present study was to evaluate the effect of thioglycosides on human SGLT1 and SGLT2. For this purpose, stably transfected Chinese hamster ovary (CHO) cells expressing human SGLT1 and SGLT2 were used. The inhibitory effect of thioglycosides was assessed in transport studies and membrane potential measurements, using α-methyl-glucoside uptake and fluorescence resonance energy trans-fer, respectively. We found that some thioglycosides inhibited hSGLT more strongly than phlorizin. Specifically, thioglycoside I (phenyl-1’-thio-β-D-glucopyranoside) inhibited hSGLT2 stronger than hSGLT1 and to a larger extent than phlorizin. Thioglycoside VII (2-hydroxymethyl-phenyl-1’-thio-β-D-galacto-pyranoside) had a pro-nounced inhibitory effect on hSGLT1 but not on hSGLT2. Kinetic studies confirmed the inhibitory effect of these thioglycosides on hSGLT1 or hSGLT2, demonstrating competitive inhibition as the mechanism of action. There-fore, these thioglycosides represent promising therapeutic agents for the control of hyperglycemia in patients with diabetes. Key words: Thioglycoside, sodium-dependent glucose transport, α-methyl-glucoside uptake, fluorescence resonance energy transfer, diabetes, hyperglycemia 1. Introduction Diabetes mellitus is characterized by reduced insulin secretion from pancreatic β-cells (type 1 diabe-tes) [1] or deficient insulin action (type 2 diabetes) [2], both causing an increase in blood glucose concentra-tion. High blood glucose (hyperglycemia) represents the main pathogenic factor for the development of diabetic complications including coronary heart dis-ease, retinopathy, nephropathy, and neuropathy [3, 4]. In addition, chronic hyperglycemia leads to progres-sive impairment of insulin secretion and to insulin resistance of peripheral tissues (referred to as glucose toxicity) [1, 2, 5, 6]. As a consequence, the treatment of diabetes has been mainly focused on maintaining normal blood glucose levels. For that purpose either insulin or Hormonal Control of Osmoregulatory Functions Hormonal Control of Osmoregulatory Functions Bởi: OpenStaxCollege While the kidneys operate to maintain osmotic balance and blood pressure in the body, they also act in concert with hormones Hormones are small molecules that act as messengers within the body Hormones are typically secreted from one cell and travel in the bloodstream to affect a target cell in another portion of the body Different regions of the nephron bear specialized cells that have receptors to respond to chemical messengers and hormones [link] summarizes the hormones ... Secretion of GnRH by the hypothalamus is inhibited by low levels of estradiol but stimulated by high levels of estradiol 4/9 Hormonal Control of Human Reproduction Just prior to the middle of the... glands that deteriorated during the end of the last cycle Art Connection 3/9 Hormonal Control of Human Reproduction The ovarian and menstrual cycles of female reproduction are regulated by hormones.. .Hormonal Control of Human Reproduction Hormones control sperm production in a negative feedback system A negative feedback system occurs in the male with rising levels of testosterone