Normal Human Reproduction Research Articles

МЕХАНІЗМ РЕАЛІЗАЦІЇ ДЕРЖАВНИХ СТАНДАРТІВ І ГАРАНТІЙ СОЦІАЛЬНОГО РОЗВИТКУ

Introduction. The economic recession and the growing number of poor people, including the able-bodied, have opened up a complex of contradictions and exacerbated the internal dysfunctions of the social protection system, a mandatory element of which is state social standards and guaran-tees. Social guarantees determine the degree of state responsibility to its citizens and provide a certain standard of living for all segments of the population. An effective and efficient system of social guarantees, as well as its proper financial support will increase the welfare of citizens. The purpose of scientific research is to determine the mechanism of formation and implementation of state social standards and guarantees, analysis of their financial support. Methodology. In the course of research system, structural methods, and also methods of comparison, the analysis and synthesis, induction and deduction have been used. Results. The article considers the economic essence and legal regulation of state social guarantees. The problematic issues of formation and implementation of state social guarantees are singled out and analyzed. The dynamics of state social guarantees for 2000-2019 is given. Peculiarities of determining the size of the subsistence minimum as an important parameter of the state policy of social and economic development are investigated. The role of the minimum wage and its relationship with the subsistence level has been identified. The sources of financial support of social guarantees are characterized. The main directions of improving the mechanism of state guarantees realization of social development are determined. Conclusions. In the process of harmonizing the population’s consumption of the set of vital goods between the state and society, the system foundations of state social standards and guarantees are laid, which are formed depending on the level of economic development, historical traditions, types of socio-economic system, gross domestic product redistribution model. Insufficient effectiveness of the implementation mechanism of state standards and guarantees of social development is caused by limited financial security, as well as existing problems of substantive characteristics of basic concepts, the solution of which will streamline the terms used and improve the quality of state social standards and guarantees. To ensure the effective use of the subsistence level, it is necessary to constantly revise the structure of standards for calculating its components, update sets of goods and services taking into account the current living conditions of all categories of the population, adjust the ratio of food, non-food goods and services according to real cost indicators, taking into account the needs of normal human reproduction, the dynamics of change in the average family size for the relevant period. Key words: state social standards, state social guarantees, social norms, subsistence level, minimum wage, minimum pension, indexation, social protection.

Defining embryo donation: an Ethics Committee opinion

Building families through the adoption of children has been supported by human society throughout history. The ethical appropriateness of patients donating embryos to other patients for family building, or for research, is well established and is affirmed by this Committee. The use of the term ''adoption'' for embryos is inaccurate and should be avoided. This document replaces the ASRM Ethics Committee statement by the same name, last published in 2013 (Fertil Steril 2013;99:1846-7).

Molecular Modeling of Neurokinin B and Tachykinin NK3 Receptor Complex

The tachykinin receptor NK₃ is a member of the rhodopsin family of G-protein coupled receptors. The NK₃ receptor has been regarded as an important drug target due to diverse physiological functions and its possible role in the pathophysiology of psychiatric disorders, including schizophrenia. The NK3 receptor is primarily activated by the tachykinin peptide hormone neurokinin B (NKB) which is the most potent natural agonist for the NK₃ receptor. NKB has been reported to play a vital role in the normal human reproduction pathway and in potentially life threatening diseases such as pre-eclampsia and as a neuroprotective agent in the case of neurodegenerative diseases. Agonist binding to the receptor is a critical event in initiating signaling, and therefore a characterization of the structural features of the agonists can reveal the molecular basis of receptor activation and help in rational design of novel therapeutics. In this study a molecular model for the interaction of the primary ligand NKB with its G-protein coupled receptor NK₃ has been developed. A three-dimensional model for the NK₃ receptor has been generated by homology modeling using rhodopsin as a template. A knowledge based docking of the NMR derived bioactive conformation of NKB to the receptor has been performed utilizing limited ligand binding data obtained from photoaffinity labeling and site-directed mutagenesis studies. A molecular model for the NKB-NK₃ receptor complex obtained sheds light on the topographical features of the binding pocket of the receptor and provides insight into the biochemical data currently available for the receptor.

The Reproductive System at a Glance, 3rd edn

This book fulfils a useful niche within the ‘at a glance series’; indeed, as the title implies, it is a repository of information. It enables the medical student to cut down on the time-consuming practice of trolling through major textbooks to get the basic information required for getting on top of the subject, and as a revision source for exam preparation. It will also be an invaluable resource for midwives and nurses working in reproductive medicine. ‘The Reproductive System at a Glance’ is split into two parts: Part 1, Normal Human Reproduction and Part 2, Human Reproductive Disorders. This immediately partitions a complex subject into manageable and easily accessible domains and avoids the danger of the reader getting ‘side-tracked’. For example, if one is reading Phenotypic Sex Differentiation in Part 1, this doesn't become complicated by abnormalities, which are dealt with separately in Part 2. Part 1 is divided into twenty-five chapters and Part 2 into twenty-three chapters. Each chapter consists of two substantially packed pages. This is a nice compact source text, with plenty of good labelled and coloured diagrams. However, the preface of the book is perhaps a little misleading in that it says the book consists of twenty-five chapters in Part 1, in which it covers normal human reproduction, commencing with embryology. This it clearly doesn't, as the first chapter is on the pituitary gland. One has to wait until chapter six, in which the topic is on ‘Gonadal Development in the Embryo’. Chapters one to four deal with the importance of reproductive hormones - their sources and mechanisms of action. This is followed by reproductive genetics, gonadal development, and sex differentiation. In chapters eight to eleven the gross and microscopic anatomy of the system is discussed, and here one must be aware of slight differences in nomenclature between American and UK terminology: in the chapter ‘Gross anatomy of the female reproductive tract’, the intramural parts of the isthmus region of the uterine (Fallopian) tubes are called cornua (horns). The chapters continue in a sequential series, covering puberty, male reproductive physiology, menstrual cycle, sexual response, fertilisation, and pregnancy through to labour and lactation. Chapters twenty-four and twenty-five deal with the menopause and contraception. Chapters twenty-six onwards deal with reproductive system disorders, beginning with abnormalities of male and female development, including a section on gender assignment. Other chapters include precocious puberty, amenorrhoea, and sexual dysfunction, for which the authors use a wonderful, easily understood diagram. Infertility, pregnancy risks with multiple gestations, pregnancy loss, labour abnormalities, and pre-eclampsia are also included. The chapter dealing with benign and malignant diseases of the breast has a very nice table with the determinants of breast cancer and the relative risks. Testicular tumours and diseases of the prostate are covered next, followed by chapters covering ovarian neoplasms, endometrial and cervical cancers, genetic imprinting and reproductive tract tumours. The final three chapters deal with sexually transmitted diseases of both bacterial and viral origin. The book ends with a bank of MCQs with answers. This will be very useful for the student when revising for exams and for self-testing after having read the relevant chapter. I have a few minor criticisms, not on content but on layout. The font size for the ‘contents’ list is too small; in contrast, the ‘table and figure acknowledgements’, have large and well-spaced text. The split into Parts 1 and 2 would have been helped visually by inserting a page between the continuous chapters, i.e. a page with the heading ‘Part 2’ between chapters 25 and 26. But these are minor cavils to this otherwise positive review. ‘The Reproductive System at a Glance’ will be particularly useful for those who want a user-friendly overview of both normal and abnormal anatomy and physiology of the male and female reproductive systems.

Molecular Modeling of Neurokinin B and Neurokinin-3 Receptor Complex

The Neurokinin-3 (NK-3) receptor is a member of the Rhodopsin family of G-protein coupled receptors. NK-3 receptor has been regarded as an important drug target due to diverse physiological functions and its possible role in the pathophysiology of psychiatric disorders, including schizophrenia. NK-3 receptor is primarily activated by the tachykinin peptide hormone Neurokinin B (NKB), the most potent natural agonist for the NK-3 receptor. NKB has been reported to play a vital role in the normal human reproduction pathway, potentially life threatening disease such as pre eclampsia and as a neuroprotective agent in case of neurodegenerative diseases. Agonist binding to the receptor is a crucial event in initiating signaling and therefore characterization of the structural features of the agonists can reveal the molecular basis of receptor activation and help in rational design of novel therapeutics. In this study a molecular model for the interaction of the primary ligand NKB with its G-protein coupled receptor NK-3 has been developed. A three-dimensional model for the NK-3 receptor has been generated by homology modeling using rhodopsin as a template. A knowledge based docking of the NMR derived bioactive conformation of NKB to the receptor has been performed utilizing limited ligand binding data obtained from the photo-affinity labeling and site- directed mutagenesis studies. A molecular model for the NKB-NK-3 receptor complex thus obtained sheds light on the topographical features of the binding pocket of the receptor and provides insight into the biochemical data currently available for the receptor. The results of the receptor modeling studies have been used to discuss the molecular determinants for NK-3 receptor selectivity.

Introduction to special issue on implantation

Introduction to special issue on implantation

Genetic expression by fetal chorionic villi during the first trimester of human gestation

Objective: The growth and differentiation of the embryo and the contiguous placental structures are fundamental to human reproduction and survival. Little is known, however, about the genetic control of these processes during early human development. Normal placentation is the result of a well-orchestrated sequence of events that consists of cellular adhesion and limited invasion controlled by relatively unknown genetic processes. We hypothesized that genes expressed by first-trimester chorionic villi constitute critical regulators of placentation and hence of early human development. Our objective was therefore to isolate and characterize genes, both known and unknown, expressed by the human placenta during the first trimester. Study Design: Tissues collected consisted of placental material collected during first-trimester elective pregnancy terminations. Fetal chorionic villi were separated grossly from maternal decidual and quickly frozen in liquid nitrogen for ribonucleic acid preservation. Tissues from different gestational ages were kept separate. Total ribonucleic acid was extracted, messenger ribonucleic acid was isolated, and complementary deoxyribonucleic acid was synthesized. Complementary deoxyribonucleic acid was cloned into the ZAP Express λ vector (Stratagene, La Jolla, Calif). Automated sequencing of random plaques was done. Sequence homology was searched for with the Basic Local Assignment Search Tool to search the Genbank database (National Center for Biotechnology Institute, Bethesda, Md). In the event that a known gene sequence was derived, no further workup was undertaken. If no homology was identified, the complete complementary deoxyribonucleic acid insert was sequenced in its entirety. Novel genes were further characterized by tissue-specific patterns, cellular localization, and chromosomal location. Expression by fetal villi was confirmed by reverse transcriptase polymerase chain reaction. Results: We isolated a number of genes known to be expressed at the maternal-fetal interface. Seventeen of 186 random clones were >1 kilobase in length and did not display homology with known genes, and these may therefore constitute novel genes critical for placentation. One of the clones from a human chorionic villi complementary deoxyribonucleic acid library at 12 weeks’ gestation is a 7-kilobase gene that is also abundantly expressed in human fetal brain, lung, liver, and kidney. In situ hybridization localized the transcript to the fetal renal glomerulus. Conclusions: Our findings indicate that the placenta serves as a rich source for potential novel gene expression. Seventeen clones were >1 kilobase in length and are potential novel genes involved in early first-trimester placentation. One of these 17 potential novel genes is expressed in abundance in several fetal tissues, which suggests a role in early human fetal development. Other potential novel genes are currently being characterized. The powerful molecular techniques that we used to isolate genes expressed by early fetal chorionic villi will lead us to a better understanding of the genetic control of normal human reproduction. They also may be used to study obstetric and other human disease. (Am J Obstet Gynecol 2000;183:706-11.)

Isolation and identification of trophoblast lymphocyte cross-reactive (TLX) antigens from human lymphocytes

It has been proposed that allotypic trophoblast lymphocyte cross-reactive (TLX) antigens are involved in the maintenance of normal human reproduction. Despite such a potentially important role for TLX antigens, isolation of human TLX proteins has not yet been reported. As an initial step toward elucidation of the structure and function of TLX antigens, we have isolated TLX proteins from Lubrol-solubilized lymphocytes (termed "wTLX") by anti-trophoblast membrane-Sepharose immunoaffinity chromatography. Using Ouchterlony immunodiffusion and immunoelectrophoresis, we have identified an immunoreactive wTLX antigen which forms a single immunoprecipitation line against absorbed anti-trophoblast membrane. From 17.5% sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analyses, a 35-kDa band was determined to be a major protein band in the immunoaffinity-isolated wTLX fraction, along with multiple minor wTLX bands. These results suggest the possible existence of antigenic polymorphism of TLX, with predominant expression of the 35-kDa wTLX antigen in lymphocytes. The strong staining of the TLX antigens with Coomassie Brilliant Blue and Amido Black indicates they are largely proteins. Co-isolation of beta 2-microglobulin in the immunoaffinity-isolated wTLX pool could imply that the wTLX antigens may be unique class I HLA-like antigens. This possibility has yet to be resolved.

RECURRENT PREGNANCY LOSS

Normal human reproduction is an inefficient process with only 22.8% of conceptive matings resulting in live birth (Fig. 1) (1,2). Miscarriages are the most common complication of pregnancy, affecting 15% of women (3). Loss of pregnancy is a physically and emotionally challenging ordeal. When pregnancy loss is repetitive, these feelings are magnified and the result is a distressing and frustrating problem for both the patients and the physicians. Recurrent pregnancy losses can occur early or late in the pregnancy. Early pregnancy losses are losses of embryos during the first trimester of pregnancy and have been termed abortions or miscarriages. Although most miscarriages are sporadic and not repetitive, there is a subset of couples that suffer recurrent miscarriage. Although the risk of miscarriage increases with maternal age, overall 15% of pregnancies miscarry. Approximately 13% of all recognized first pregnancies are lost. The risk of a second consecutive miscarriage is only slightly increased to 17%. However, the risk of miscarriage after two consecutive pregnancy losses rises to between 35 and 40% and continues to rise with each subsequent miscarriage (4). As many as 5% of all couples conceiving experience two consecutive miscarriages and 2% have three or more consecutive losses. Late pregnancy losses are losses of fetuses after the first trimester of pregnancy. Late pregnancy losses occur far less frequently than early pregnancy losses and comprise only 1% of pregnancies. Late pregnancy losses are usually associated with incompetent cervix, premature rupture of membranes, preterm labor, intrauterine growth retardation, or placental abruption.