Sexual Differentiation
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Ethical Principles and Recommendations for the Medical Management of Differences of Sex Development (DSD)/Intersex in Children and Adolescents
Eur J Pediatr DOI 10.1007/s00431-009-1086-x ORIGINAL PAPER Ethical principles and recommendations for the medical management of differences of sex development (DSD)/intersex in children and adolescents Claudia Wiesemann & Susanne Ude-Koeller & Gernot H. G. Sinnecker & Ute Thyen Received: 8 March 2009 /Accepted: 9 September 2009 # The Author(s) 2009. This article is published with open access at Springerlink.com Abstract The medical management of differences of sex the working group “Bioethics and Intersex” within the development (DSD)/intersex in early childhood has been German Network DSD/Intersex, which are presented in detail. criticized by patients’ advocates as well as bioethicists from Unlike other recommendations with regard to intersex, these an ethical point of view. Some call for a moratorium of any guidelines represent a comprehensive view of the perspectives feminizing or masculinizing operations before the age of of clinicians, patients, and their families. consent except for medical emergencies. No exhaustive Conclusion The working group identified three leading ethical guidelines have been published until now. In particular, ethical principles that apply to DSD management: (1) to the role of the parents as legal representatives of the child is foster the well-being of the child and the future adult, (2) to controversial. In the article, we develop, discuss, and present uphold the rights of children and adolescents to participate ethical principles and recommendations for the medical in and/or self-determine decisions that affect them now or management of intersex/DSD in children and adolescents. later, and (3) to respect the family and parent–child We specify three basic ethical principles that have to be relationships. -
Te2, Part Iii
TERMINOLOGIA EMBRYOLOGICA Second Edition International Embryological Terminology FIPAT The Federative International Programme for Anatomical Terminology A programme of the International Federation of Associations of Anatomists (IFAA) TE2, PART III Contents Caput V: Organogenesis Chapter 5: Organogenesis (continued) Systema respiratorium Respiratory system Systema urinarium Urinary system Systemata genitalia Genital systems Coeloma Coelom Glandulae endocrinae Endocrine glands Systema cardiovasculare Cardiovascular system Systema lymphoideum Lymphoid system Bibliographic Reference Citation: FIPAT. Terminologia Embryologica. 2nd ed. FIPAT.library.dal.ca. Federative International Programme for Anatomical Terminology, February 2017 Published pending approval by the General Assembly at the next Congress of IFAA (2019) Creative Commons License: The publication of Terminologia Embryologica is under a Creative Commons Attribution-NoDerivatives 4.0 International (CC BY-ND 4.0) license The individual terms in this terminology are within the public domain. Statements about terms being part of this international standard terminology should use the above bibliographic reference to cite this terminology. The unaltered PDF files of this terminology may be freely copied and distributed by users. IFAA member societies are authorized to publish translations of this terminology. Authors of other works that might be considered derivative should write to the Chair of FIPAT for permission to publish a derivative work. Caput V: ORGANOGENESIS Chapter 5: ORGANOGENESIS -
History of the Research on Sex Determination
Review Article ISSN: 2574 -1241 DOI: 10.26717/BJSTR.2020.25.004194 History of The Research on Sex Determination Jacek Z Kubiak1,2, Malgorzata Kloc3-5 and Rafal P Piprek6* 1UnivRennes, CNRS, UMR 6290, IGDR, Cell Cycle Group, F-35000 Rennes, France 2Military Institute of Hygiene and Epidemiology, ZMRiBK, Warsaw, Poland 3The Houston Methodist Research Institute, USA 4Department of Surgery, The Houston Methodist Hospital, USA 5University of Texas, MD Anderson Cancer Center, USA 6Department of Comparative Anatomy, Institute of Zoology and Biomedical Research, Jagiellonian University, Poland *Corresponding author: Rafał P Piprek, Department of Comparative Anatomy, Institute of Zoology and Biomedical Research, Jagiellonian University, Poland ARTICLE INFO Abstract Received: Published: January 28, 2020 Since the beginning of the humanity, people were fascinated by sex and intrigued by February 06, 2020 how the differences between sexes are determined. Ancient philosophers and middle Citation: age scholars proposed numerous fantastic explanations for the origin of sex differences in people and animals. However, only the development of the modern scientific methods Jacek Z Kubiak, Malgorzata Kloc, allowed us to find, on the scientific ground, the right answers to these questions. In this Rafal P Piprek. History of The Research on review article, we describe the history of these discoveries, and which major discoveries allowed the understanding of the origin of sex and molecular and cellular basis of the Sex Determination. Biomed J Sci & Tech Res -
Comparative Reproductive Biology
Comparative Reproductive Biology Edited by Heide Schatten, PhD Gheorghe M. Constantinescu, DVM, PhD, Drhc Comparative Reproductive Biology Comparative Reproductive Biology Edited by Heide Schatten, PhD Gheorghe M. Constantinescu, DVM, PhD, Drhc Heide Schatten, PhD, is an Associate Professor at the University of Missouri, Columbia. She is well published in the areas of cytoskeletal regulation in somatic and reproductive cells and on cytoskeletal abnormalities in cells affected by disease, cellular and molecular biology, cancer biology, reproductive biology, developmental biology, microbiology, space biology, and microscopy. A member of the American Society for Cell Biology, American Association for the Advancement of Science, Microscopy Society of America, and American Society for Gravitational and Space Biology, she has received numerous awards including grant awards from NSF, NIH, and NASA. Gheorghe M. Constantinescu, DVM, PhD, Drhc, is a Professor of Veterinary Anatomy and Medical Illustrator at the College of Veterinary Medicine of the University of Missouri-Columbia. He is a member of the American, European and World Associations of Veterinary Anatomists and also author of more than 380 publications, including Clinical Anatomy for Small Animal Practitioners (Blackwell, 2002) translated in three languages. During his career of more than 50 years, he has been honored by numerous invited presentations, awards, diplomas, and certificates of recognition. ©2007 Blackwell Publishing All rights reserved Blackwell Publishing Professional 2121 -
Disorders of Sexual Differentiation: a Study on the Incidence and Types of Female Pseudo Hermaphrodites J.Radhika *1, C.Bhuvaneswari 2, Arudyuti Chowdhury 3
International Journal of Integrative Medical Sciences, Int J Intg Med Sci 2016, Vol 3(12):455-60. ISSN 2394 - 4137 DOI: http://dx.doi.org/10.16965/ijims.2016.156 Original Research Article Disorders of Sexual Differentiation: A study on the Incidence and Types of Female Pseudo Hermaphrodites J.Radhika *1, C.Bhuvaneswari 2, Arudyuti Chowdhury 3. *1 Associate Professor, Department of Anatomy, SRM Medical College Hospital & Research Centre, SRM University, Kattankulathur, India. 2 Assistant Professor, Department of Anatomy, SRM Medical College Hospital & Research Centre, SRM University, Kattankulathur, India. 3 Professor, Prasad Institute of Medical Sciences, Lucknow, India. ABSTRACT Aim: The present study was done to find out the prevalence of disorders of sexual development in our population and the genetic and environmental factors in the causation of disorders. Primarily, the study focused on the incidence and types of Female Pseudo Hermaphrodites. Materials and Methods: The present study included 300 cases over a period of 3 years in the Institute of Obstetrics and Gynaecology, Egmore. Of these 300 cases, 29.3% were identified as Female pseudo hermaphrodite by examining the external and internal genitalia and through Karyotypes, ultrasound and hormonal assay. Results and Conclusion: The increased incidence of Female Pseudo hermaphrodite was found to be due to avoidable factors except for a few cases. This highlights the importance of early diagnosis for assigning appropriate gender without causing much social and emotional problems. KEY WORDS: Ambiguous Genitalia, Female Pseudo Hermaphrodite, Masculinization Of External Genitalia, Karyotype. Address for correspondence: Dr.J.Radhika, M.D, Ph.D, Associate Professor, Department of Anatomy, SRM Medical College Hospital & Research Centre, SRM University, Kattankulathur, India. -
Sexual Differentiation of the Vertebrate Nervous System
T HE S EXUAL B RAIN REVIEW Sexual differentiation of the vertebrate nervous system John A Morris, Cynthia L Jordan & S Marc Breedlove Understanding the mechanisms that give rise to sex differences in the behavior of nonhuman animals may contribute to the understanding of sex differences in humans. In vertebrate model systems, a single factor—the steroid hormone testosterone— accounts for most, and perhaps all, of the known sex differences in neural structure and behavior. Here we review some of the events triggered by testosterone that masculinize the developing and adult nervous system, promote male behaviors and suppress female behaviors. Testosterone often sculpts the developing nervous system by inhibiting or exacerbating cell death and/or by modulating the formation and elimination of synapses. Experience, too, can interact with testosterone to enhance or diminish its effects on the central nervous system. However, more work is needed to uncover the particular cells and specific genes on which http://www.nature.com/natureneuroscience testosterone acts to initiate these events. The steps leading to masculinization of the body are remarkably con- Apoptosis and sexual dimorphism in the nervous system sistent across mammals: the paternally contributed Y chromosome Lesions of the entire preoptic area (POA) in the anterior hypothala- contains the sex-determining region of the Y (Sry) gene, which mus eliminate virtually all male copulatory behaviors3,whereas induces the undifferentiated gonads to form as testes (rather than lesions restricted to the sexually dimorphic nucleus of the POA (SDN- ovaries). The testes then secrete hormones to masculinize the rest of POA) have more modest effects, slowing acquisition of copulatory the body. -
Focus on Stem Cells Germ Cells from Mouse and Human Embryonic Stem Cells
REPRODUCTIONREVIEW Focus on Stem Cells Germ cells from mouse and human embryonic stem cells Behrouz Aflatoonian and Harry Moore Centre for Stem Cell Biology, University of Sheffield, Sheffield S10 2UH, UK Correspondence should be addressed to H Moore; Email: [email protected] Abstract Mammalian gametes are derived from a founder population of primordial germ cells (PGCs) that are determined early in embryogenesis and set aside for unique development. Understanding the mechanisms of PGC determination and differentiation is important for elucidating causes of infertility and how endocrine disrupting chemicals may potentially increase susceptibility to congenital reproductive abnormalities and conditions such as testicular cancer in adulthood (testicular dysgenesis syndrome). Primordial germ cells are closely related to embryonic stem cells (ESCs) and embryonic germ (EG) cells and comparisons between these cell types are providing new information about pluripotency and epigenetic processes. Murine ESCs can differentiate to PGCs, gametes and even blastocysts – recently live mouse pups were born from sperm generated from mESCs. Although investigations are still preliminary, human embryonic stem cells (hESCs) apparently display a similar developmental capacity to generate PGCs and immature gametes. Exactly how such gamete-like cells are generated during stem cell culture remains unclear especially as in vitro conditions are ill-defined. The findings are discussed in relation to the mechanisms of human PGC and gamete development and the biotechnology of hESCs and hEG cells. Reproduction (2006) 132 699–707 Introduction indicate that human embryonic stem cells (hESCs) most likely display a similar developmental capacity (Clark Detailed investigations of the earliest stages of germ cell et al. -
Insights from Male Germ Cell Differentiation
Cell Death & Differentiation (2021) 28:2296–2299 https://doi.org/10.1038/s41418-021-00812-0 COMMENT Natural selection at the cellular level: insights from male germ cell differentiation 1 1 Daniel H. Nguyen ● Diana J. Laird Received: 9 February 2021 / Revised: 20 May 2021 / Accepted: 20 May 2021 / Published online: 2 June 2021 © The Author(s) 2021. This article is published with open access Waddington’s concept of differentiation as an epigenetic The germline is a fascinating context for investigating landscape provides an enduring metaphor visualizing the the consequences of heterogeneity on differentiation and options faced by stem and progenitor cells. However, cell fate. As fetal germ cells establish the gametes, their increasing understanding of cellular heterogeneity poses population dynamics can greatly influence inheritance. The new questions about the identities and behaviors of the cells conflict between diversity and orderly differentiation looms beginning this process. We now recognize a greater diver- centrally over germline development. In mouse embryos, sity of initial states for individual progenitor cells, which germ cells undertake an epic journey, from specification may affect their trajectories and disrupt progress entirely. through sex differentiation, replete with opportunities for 1234567890();,: 1234567890();,: Here, we consider how developmental selection occurs heterogeneity to develop and be assessed. Notably, an when heterogeneity in differentiating progenitors produces excess of germ cells is produced and then pruned by pro- divergent cellular outcomes of survival versus elimination. grammed cell death [5]. This occurs across diverse species Heterogeneity is a fundamental property of biological regardless of sex, suggesting that differential fitness and systems. Individual cell properties like location or cell cycle elimination are critical. -
Reproduction – Sexual Differentiation
Reproduction – sexual differentiation Recommended textbook for reproductive biology M.H. Johnson & B.J. Everitt, Essential Reproduction, Blackwell. Third edition (1988) or later. Topics to think about Why do many organisms have sex? Why are there two sexes (and not one, or three)? How does the difference be- tween gametes contribute to the different reproductive strategies of male and female? Are the mother and fetus working towards the same goals? When might their goals differ? How might such differ- ences lead to problems, and to sex-linked phenotypic differences? The Red Queen, by Matt Ridley (1994), is a fascinating look at these questions. Highly recommended, though has little direct bearing on your course. Genetic determinants of sex • Humans have 46 chromosomes: 22 pairs of autosomes and one pair of sex chromosomes. • The male has one X and one Y sex chromosome (the heterogametic sex). The female has two X chromosomes (ho- mogametic). • The Y chromosome is small and carries few (2) genes1 – far too few to make a testis, for example. Its function is to confer maleness on the embryo, and it does so by altering the expression of genes on other chromosomes. The criti- cal gene is on a region of the short arm of the Y chromosome and is called testis-determining factor (TDF). If this is present, the embryo will be gonadally male; if it is absent the default is for the embryo to develop as a female. • The precise mechanism by which the TDF gene causes initiates testicular development is unknown. • The X chromosome is large and carries many (>50) genes. -
Ovarian Insufficiency and CTNNB1 Mutations Drive Malignant Transformation of Endometrial Hyperplasia with Altered PTEN/PI3K Activities
Ovarian insufficiency and CTNNB1 mutations drive malignant transformation of endometrial hyperplasia with altered PTEN/PI3K activities Jumpei Terakawaa,b,1,2, Vanida Ann Sernaa,b,1, Makoto Mark Taketoc, Takiko Daikokud, Adrian A. Suarezb,e, and Takeshi Kuritaa,b,3 aDepartment of Cancer Biology and Genetics, Ohio State University, Columbus, OH 43210; bThe Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210; cDivision of Experimental Therapeutics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, 606-8506 Kyoto, Japan; dDivision of Transgenic Animal Science, Advanced Science Research Center, Kanazawa University, 920-8640 Kanazawa, Japan; and eDepartment of Pathology, Ohio State University, Columbus, OH 43210 Edited by Patricia K. Donahoe, Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Department of Surgery, Harvard Medical School, Boston, MA, and approved January 23, 2019 (received for review August 28, 2018) Endometrioid endometrial carcinomas (EECs) carry multiple driver PI3K (5). However, PTEN and PI3K (PIK3CA or PIK3R1)mu- mutations even when they are low grade. However, the biological tations co-occurred in 67% (59/88) of CL-EECs. This observation significance of these concurrent mutations is unknown. We explored questions the widely accepted concept that the loss of PTEN and the interactions among three signature EEC mutations: loss-of- activation of PI3K have synonymous effects on cellular physiology, as function (LOF) mutations in PTEN, gain-of-function (GOF) mutations they catalyze opposite reactions: PI3K converts phosphatidylinositol of phosphoinositide 3-kinase (PI3K), and CTNNB1 exon 3 mutations, (4,5)-biphosphate (PIP2) to phosphatidylinositol (3,4,5)-trisphosphate utilizing in vivo mutagenesis of the mouse uterine epithelium. -
Germ-Line Immortality
COMMENTARY Germ-line immortality Martin M. Matzuk* Departments of Pathology, Molecular and Cellular Biology, and Molecular and Human Genetics, and Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030 ajor advances in stem cell Table 1. Pathway of differentiation in males research have occurred over Spermatogonial Differentiated the last decades. Progress Markers ES cells ¡ PGCs ¡ Gonocytes ¡ stem cells ¡ spermatogonia has included the generation Mof lines of human and mouse embryonic Kit ϩϩϩ͞– – (low) ϩ ϩ ϩϩ stem (ES) cells and the identification and Thy-1 ? (low) – Oct4 ϩϩ ϩ ϩ – purification of stem cells for multiple Plzf ϩ (low)* ϩ* ϩϩ – independent lineages. Recent studies by GCNA1 – ϩ† ϩϩ ϩ Brinster and colleagues in this issue of TNAP ϩ (high) ϩ (high) – ϩ (low)͞–– PNAS (1) also suggest that the reproduc- RET ϩ (low)* ? ? ϩ – ␣ ϩ ϩ tive potential of an organism can be pro- GFR 1 (low)* ? ? (low) – NCAM ϩ ? ϩϩ ? longed indefinitely by using germ-line stem cells. It even appears that eggs and Markers that are known to be expressed (ϩ) or absent (–) in many of the pathway cells are listed. GCNA1, sperm can develop from cultured mouse germ cell nuclear antigen 1; TNAP, tissue-nonspecific alkaline phosphatase; NCAM, neural cell adhesion ES cells (2–4). Although gametes derived molecule. in vitro have yet to prove their develop- *mRNA levels. † mental potential, these studies suggest Postmigratory PGCs only. that ES cells and germ-line stem cells share many characteristics. ent males. The process was surprisingly KitϪ Sca-IϪ ␣6-integrinϩ ␣v-integrinϪ/dim In most mammalian females, meiosis efficient, with up to 100% of the injected (9, 10). -
441 2004 Article BF00572101.Pdf
(Department of Zoology, University of Michigan.) CONTRIBUTIONS ON THE DEVELOPMENT OF THE REPRODUCTIVE SYSTEM IN THE I~USK TURTLE, STERNOTHERUS ODORATUS (LATREILLE). II. GONADOGENESIS AND SEX DIFFERENTIATION1. By PAUL L. RISLEY. With 41 figures in the text. (Eingegangen am 5. Januar 1933.) Table of Contents. gage I. Introduction .......................... 493 II. Materials and methods ...................... 494 III. Observations .......................... 495 A. The undifferentiated or indifferent gonads ........... 495 B. The development of cortex and medulla (The bisexual or indetermin- ate gonads) ......................... 501 C. Sex differentiation ...................... 509 1. Macroscopic observations .................. 509 2. Microscopic observations ................. 515 a) The development of the ovary .............. 515 b) The development of the testis .............. 519 c) Sex reversal ...................... 523 IV. Literature and discussion .................... 525 V. Summary and conclusions .................... 538 VI. Literature cited ......................... 540 I. Introduction. In the previous contribution (1933) of this series, I followed the embryonic origin and migration of the primordial germ cells from an extraregional position in the posterior and lateral margins of the area pellucida to a resident location in the undifferentiated germ glands. In this paper, the investigation of the problem of the embryonic history of the germ cells is extended to include the problems of gonadogenesis and sex differentiation, which