Talk:Genital System - Abnormalities: Difference between revisions
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Decreased production of glucocorticoids and sex steroids, resulting in sexual infantilism in 46,XX females and ambiguous genitalia in 46,XY males | Decreased production of glucocorticoids and sex steroids, resulting in sexual infantilism in 46,XX females and ambiguous genitalia in 46,XY males | ||
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Glossary Links
Cite this page: Hill, M.A. (2024, May 6) Embryology Genital System - Abnormalities. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Genital_System_-_Abnormalities |
http://bestpractice.bmj.com/best-practice/monograph/1104/basics.html
2016
| Congenital Adrenal Hyperplasia | |||
|---|---|---|---|
| Type | Enzyme Deficiency | Female | Male |
| classic virilizing adrenal hyperplasia | 21-hydroxylase, 11-beta-hydroxylase, or 3-beta-hydroxysteroid dehydrogenase |
ambiguous genitalia at birth - complete or partial fusion of the labioscrotal folds and a phallic urethra to clitoral enlargement (clitoromegaly), partial fusion of the labioscrotal folds, or both | normal genitalia, present at age 1-4 weeks with salt wasting (classic salt-wasting adrenal hyperplasia) |
| simple virilizing adrenal hyperplasia | mild 21-hydroxylase | identified later in childhood because of precocious pubic hair, clitoral enlargement (clitoromegaly), or both, often accompanied by accelerated growth and skeletal maturation | early genital development (pubic hair and/or phallic enlargement) accelerated growth and skeletal maturation |
| nonclassic adrenal hyperplasia | milder deficiencies of 21-hydroxylase or 3-beta-hydroxysteroid dehydrogenase |
present at puberty or adult with infrequent menstruation (oligomenorrhea), abnormal hair growth (hirsutism), and/or infertility | |
| 17-hydroxylase deficiency syndrome | 17-hydroxylase deficiency or 3-beta-hydroxysteroid dehydrogenase |
rare, phenotypically female at birth do not develop breasts or menstruate in adolescence and may have hypertension | steroidogenic acute regulatory (StAR) deficiency have ambiguous genitalia or female genitalia, at puberty may lack breast development and may have hypertension |
| This is a complex steroidogenic abnormality, and the above table of clinical descriptions are provided only a guide. | |||
Decreased production of glucocorticoids and sex steroids, resulting in sexual infantilism in 46,XX females and ambiguous genitalia in 46,XY males
2105
The perinatal origins of major reproductive disorders in the adolescent: Research avenues
Placenta. 2015 Apr;36(4):341-4. doi: 10.1016/j.placenta.2015.01.003. Epub 2015 Jan 15.
Brosens I1, Ćurčić A2, Vejnović T2, Gargett CE3, Brosens JJ4, Benagiano G5.
Abstract
The fetal endometrium becomes responsive to steroid hormones around the fourth month of pregnancy starting with an oestrogenic phase, which is followed late in pregnancy by a secretory phase. Based on post-mortem studies, the endometrium at birth is secretory in only one-third of neonates and proliferative in the remaining cases. Decidual or menstrual changes are rare in fetal endometrium despite high circulating steroid hormone levels, which drop rapidly after birth. Hence, acquisition of progesterone responsiveness appears to be dependent on endometrial maturation and relative immaturity may persist in a majority of girls until the menarche and early adolescence. Two major reproductive disorders have been linked with either advanced or delayed endometrial maturation. First, early-onset endometriosis may be caused by menstruation-like bleeding in the neonate, leading to tubal reflux and ectopic implantation of endometrial stem/progenitor cells. Second, persistence of partial progesterone resistance in adolescent girls may compromise deep placentation and account for the increased risk of major obstetrical syndromes, including preeclampsia, fetal growth retardation and preterm birth. The concept of neonatal origins of common reproductive disorders poses important research challenges but also subsumes potential new preventative strategies. Copyright © 2015 Elsevier Ltd. All rights reserved. KEYWORDS: Endometriosis; Endometrium; Neonatal uterine bleeding; Obstetrical disorders; Progesterone resistance
PMID 25637411
2013
Minor hypospadias: the "tip of the iceberg" of the partial androgen insensitivity syndrome
PLoS One. 2013 Apr 30;8(4):e61824. doi: 10.1371/journal.pone.0061824. Print 2013.
Kalfa N, Philibert P, Werner R, Audran F, Bashamboo A, Lehors H, Haddad M, Guys JM, Reynaud R, Alessandrini P, Wagner K, Kurzenne JY, Bastiani F, Bréaud J, Valla JS, Lacombe GM, Orsini M, Daures JP, Hiort O, Paris F, McElreavey K, Sultan C. Source Service de Chirurgie Viscérale et Urologique Pédiatrique, Hôpital Lapeyronie, CHU de Montpellier et Université Montpellier 1, Montpellier, France ; Service d'Hormonologie, Hôpital Lapeyronie, CHU de Montpellier et Université Montpellier 1, Montpellier, France.
Abstract
BACKGROUND: Androgens are critical in male external genital development. Alterations in the androgen sensitivity pathway have been identified in severely undermasculinized boys, and mutations of the androgen receptor gene (AR) are usually found in partial or complete androgen insensitivity syndrome (AIS). OBJECTIVE: The aim of this study was to determine whether even the most minor forms of isolated hypospadias are associated with AR mutations and thus whether all types of hypospadias warrant molecular analysis of the AR. MATERIALS AND METHODS: Two hundred and ninety-two Caucasian children presenting with isolated hypospadias without micropenis or cryptorchidism and 345 controls were included prospectively. Mutational analysis of the AR through direct sequencing (exons 1-8) was performed. In silico and luciferase functional assays were performed for unreported variants. RESULTS: Five missense mutations of the AR were identified in 9 patients with glandular or penile anterior (n = 5), penile midshaft (n = 2) and penile posterior (n = 2) hypospadias, i.e., 3%: p.Q58L (c.173A>T), 4 cases of p.P392S (c.1174C>T), 2 cases of p.A475V (c.1424C>T), p.D551H (c.1651G>C) and p.Q799E (c.2395C>G). None of these mutations was present in the control group. One mutation has never been reported to date (p.D551H). It was predicted to be damaging based on 6 in silico models, and in vitro functional studies confirmed the lowered transactivation function of the mutated protein. Three mutations have never been reported in patients with genital malformation but only in isolated infertility: p.Q58L, p.P392S, and p.A475V. It is notable that micropenis, a cardinal sign of AIS, was not present in any patient. CONCLUSION: AR mutations may play a role in the cause of isolated hypospadias, even in the most minor forms. Identification of this underlying genetic alteration may be important for proper diagnosis and longer follow-up is necessary to find out if the mutations cause differences in sexual function and fertility later in life.
PMID 23637914
Nationwide Prevalence of Groin Hernia Repair
PLoS ONE 8(1): e54367. doi:10.1371/journal.pone.0054367 (2013)
Burcharth J, Pedersen M, Bisgaard T, Pedersen C, Rosenberg J
Groin hernia repair is a commonly performed surgical procedure in the western world but large-scaled epidemiologic data are sparse. Large-scale data on the occurrence of groin hernia repair may provide further understanding to the pathophysiology of groin hernia development. This study was undertaken to investigate the age and gender dependent prevalence of groin hernia repair.
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0054367
2012
NIH - Evidence-based Methodology Workshop on Polycystic Ovary Syndrome December 3–5, 2012 PCOS Draft Statement PDF
2011
The history of female genital tract malformation classifications and proposal of an updated system
Hum Reprod Update. 2011 Sep-Oct;17(5):693-705. Epub 2011 Jul 4.
Acién P, Acién MI. Source Service of Obstetrics and Gynaecology, Department of Gynaecology, University Hospital of San Juan, Alicante, Spain. acien@umh.es
Abstract
BACKGROUND: A correct classification of malformations of the female genital tract is essential to prevent unnecessary and inadequate surgical operations and to compare reproductive results. An ideal classification system should be based on aetiopathogenesis and should suggest the appropriate therapeutic strategy. METHODS: We conducted a systematic review of relevant articles found in PubMed, Scopus, Scirus and ISI webknowledge, and analysis of historical collections of 'female genital malformations' and 'classifications'. Of 124 full-text articles assessed for eligibility, 64 were included because they contained original general, partial or modified classifications. RESULTS: All the existing classifications were analysed and grouped. The unification of terms and concepts was also analysed. Traditionally, malformations of the female genital tract have been catalogued and classified as Müllerian malformations due to agenesis, lack of fusion, the absence of resorption and lack of posterior development of the Müllerian ducts. The American Fertility Society classification of the late 1980s included seven basic groups of malformations also considering the Müllerian development and the relationship of the malformations to fertility. Other classifications are based on different aspects: functional, defects in vertical fusion, embryological or anatomical (Vagina, Cervix, Uterus, Adnex and Associated Malformation: VCUAM classification). However, an embryological-clinical classification system seems to be the most appropriate. CONCLUSIONS: Accepting the need for a new classification system of genitourinary malformations that considers the experience gained from the application of the current classification systems, the aetiopathogenesis and that also suggests the appropriate treatment, we proposed an update of our embryological-clinical classification as a new system with six groups of female genitourinary anomalies.
PMID 21727142
Disorders of sex development-when and how to tell the patient
Austin J, Tamar-Mattis A, Mazur T, Henwood MJ, Rossi WC. Pediatr Endocrinol Rev. 2011 Mar;8(3):213-7; quiz 223.
Abstract Physicians and other providers are often confronted with difficult decisions in the area of disclosure. This article examines a hypothetical situation relevant to the practice of pediatric endocrinology. The parents of a child with a disorder of sex development (DSD) wish the physician to treat their child, but without revealing key medical information to the child. Herein, we will explore the legal and ethical responsibilities of a provider to disclose information to an under-age DSD patient and to provide insight on when and how to tell the patient.
PMID 21525798
The Relationship between Anogenital Distance, Fatherhood, and Fertility in Adult Men
Eisenberg ML, Hsieh MH, Walters RC, Krasnow R, Lipshultz LI.
PLoS One. 2011 May 11;6(5):e18973.
Anogenital distance (the distance from the posterior aspect of the scrotum to the anal verge) and penile length (PL) were measured using digital calipers. ANOVA and linear regression were used to determine correlations between AGD, fatherhood status, and semen analysis parameters (sperm density, motility, and total motile sperm count). Findings
A total of 117 infertile men (mean age: 35.3±17.4) and 56 fertile men (mean age: 44.8±9.7) were recruited. The infertile men possessed significantly shorter mean AGD and PL compared to the fertile controls (AGD: 31.8 vs 44.6 mm, PL: 107.1 vs 119.5 mm, p<0.01). The difference in AGD persisted even after accounting for ethnic and anthropomorphic differences. In addition to fatherhood, on both unadjusted and adjusted linear regression, AGD was significantly correlated with sperm density and total motile sperm count. After adjusting for demographic and reproductive variables, for each 1 cm increase in a man's AGD, the sperm density increases by 4.3 million sperm per mL (95% CI 0.53, 8.09, p=0.03) and the total motile sperm count increases by 6.0 million sperm (95% CI 1.34, 10.58, p=0.01). On adjusted analyses, no correlation was seen between penile length and semen parameters.
Conclusion
A longer anogenital distance is associated with fatherhood and may predict normal male reproductive potential. Thus, AGD may provide a novel metric to assess reproductive potential in men.
PMID 21589916
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092750
Pictorial essay: Congenital anomalies of male urethra in children
Indian J Radiol Imaging. 2011 Jan;21(1):38-45.
Jana M, Gupta AK, Prasad KR, Goel S, Tambade VD, Sinha U. Source Department of Radiodiagnosis, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
Abstract
Congenital anomalies of the male urogenital tract are common. Some lesions like posterior urethral valve or anterior urethral diverticulum tend to present early in infancy and are often easily diagnosed on conventional contrast voiding cystourethrograms. Other conditions like posterior urethral diverticulum or utricle can be relatively asymptomatic and therefore present late in childhood. We present the spectrum of imaging findings of common and uncommon anomalies involving the male urethra. Since the pediatric radiologist is often the first to make the diagnosis, he or she should be well aware of these conditions.
PMID 21431032
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056369
2010
Consensus in Guidelines for Evaluation of DSD by the Texas Children's Hospital Multidisciplinary Gender Medicine Team
Douglas G, Axelrad ME, Brandt ML, Crabtree E, Dietrich JE, French S, Gunn S, Karaviti L, Lopez ME, Macias CG, McCullough LB, Suresh D, Sutton VR. Int J Pediatr Endocrinol. 2010;2010:919707. Epub 2010 Oct 17.
The Gender Medicine Team (GMT), comprised of members with expertise in endocrinology, ethics, genetics, gynecology, pediatric surgery, psychology, and urology, at Texas Children's Hospital and Baylor College of Medicine formed a task force to formulate a consensus statement on practice guidelines for managing disorders of sexual differentiation (DSD) and for making sex assignments. The GMT task force reviewed published evidence and incorporated findings from clinical experience. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to assess the quality of evidence presented in the literature for establishing evidence-based guidelines. The task force presents a consensus statement regarding specific diagnostic and therapeutic issues in the management of individuals who present with DSD. The consensus statement includes recommendations for (1) laboratory workup, (2) acute management, (3) sex assignment in an ethical framework that includes education and involvement of the parents, and (4) surgical management.
PMID 20981291
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963131
46,XY DSD with Female or Ambiguous External Genitalia at Birth due to Androgen Insensitivity Syndrome, 5alpha-Reductase-2 Deficiency, or 17beta-Hydroxysteroid Dehydrogenase Deficiency: A Review of Quality of Life Outcomes
Int J Pediatr Endocrinol. 2009;2009:567430. Epub 2009 Sep 10.
Wisniewski AB, Mazur T.
Section of Pediatric Diabetes and Endocrinology, Department of Pediatrics, University of Oklahoma Health Sciences Center, 940 NE 13th Street, Room 2B2426, Oklahoma City, OK 73117, USA.
Abstract Disorders of sex development refer to a collection of congenital conditions in which atypical development of chromosomal, gonadal, or anatomic sex occurs. Studies of 46,XY DSD have focused largely on gender identity, gender role, and sexual orientation. Few studies have focused on other domains, such as physical and mental health, that may contribute to a person's quality of life. The current review focuses on information published since 1955 pertaining to psychological well-being, cognition, general health, fertility, and sexual function in people affected by androgen insensitivity syndromes, 5-alpha reductase-2 deficiency, or 17beta-hydroxysteroid dehydrogenase-3 deficiency-reared male or female. The complete form of androgen insensitivity syndrome has been the focus of the largest number of investigations in domains other than gender. Despite this, all of the conditions included in the current review are under-studied. Realms identified for further study include psychological well-being, cognitive abilities, general health, fertility, and sexual function. Such investigations would not only improve the quality of life for those affected by DSD but may also provide information for improving physical and mental health in the general population.
PMID 19956704
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777017
Special Issue: Klinefelter's Syndrome: basic science to clinic
MHR: Basic science of reprod. MedicineVolume16, Issue6
Volume 16 Issue 6 June 2010
http://molehr.oxfordjournals.org/content/16/6.toc
Ethical principles and recommendations for the medical management of differences of sex development (DSD)/intersex in children and adolescents
Eur J Pediatr. 2010 Jun;169(6):671-9. Epub 2009 Oct 20.
Wiesemann C, Ude-Koeller S, Sinnecker GH, Thyen U.
Department for Medical Ethics and History of Medicine, Göttingen University, Humboldtallee 36, 37073 Göttingen, Germany. cwiesem@gwdg.de Abstract The medical management of differences of sex development (DSD)/intersex in early childhood has been criticized by patients' advocates as well as bioethicists from an ethical point of view. Some call for a moratorium of any feminizing or masculinizing operations before the age of consent except for medical emergencies. No exhaustive ethical guidelines have been published until now. In particular, the role of the parents as legal representatives of the child is controversial. In the article, we develop, discuss, and present ethical principles and recommendations for the medical management of intersex/DSD in children and adolescents. We specify three basic ethical principles that have to be respected and substantiate them. The article includes a critical discussion of the best interest of the child and of family privacy. The argumentation draws upon recommendations by the working group "Bioethics and Intersex" within the German Network DSD/Intersex, which are presented in detail. Unlike other recommendations with regard to intersex, these guidelines represent a comprehensive view of the perspectives of clinicians, patients, and their families. CONCLUSION: The working group identified three leading ethical principles that apply to DSD management: (1) to foster the well-being of the child and the future adult, (2) to uphold the rights of children and adolescents to participate in and/or self-determine decisions that affect them now or later, and (3) to respect the family and parent-child relationships. Nine recommendations for the management of DSD indicate how these ethical principles can spelled out and balanced against each other in the clinical setting.
PMID 19841941
2009
The exstrophy-epispadias complex
Orphanet J Rare Dis. 2009 Oct 30;4:23.
Ebert AK, Reutter H, Ludwig M, Rösch WH.
Department of Pediatric Urology, University Medical Center Regensburg, Germany. anne-karoline.ebert@barmherzige-regensburg.de Abstract Exstrophy-epispadias complex (EEC) represents a spectrum of genitourinary malformations ranging in severity from epispadias (E) to classical bladder exstrophy (CEB) and exstrophy of the cloaca (EC). Depending on severity, EEC may involve the urinary system, musculoskeletal system, pelvis, pelvic floor, abdominal wall, genitalia, and sometimes the spine and anus. Prevalence at birth for the whole spectrum is reported at 1/10,000, ranging from 1/30,000 for CEB to 1/200,000 for EC, with an overall greater proportion of affected males. EEC is characterized by a visible defect of the lower abdominal wall, either with an evaginated bladder plate (CEB), or with an open urethral plate in males or a cleft in females (E). In CE, two exstrophied hemibladders, as well as omphalocele, an imperforate anus and spinal defects, can be seen after birth. EEC results from mechanical disruption or enlargement of the cloacal membrane; the timing of the rupture determines the severity of the malformation. The underlying cause remains unknown: both genetic and environmental factors are likely to play a role in the etiology of EEC. Diagnosis at birth is made on the basis of the clinical presentation but EEC may be detected prenatally by ultrasound from repeated non-visualization of a normally filled fetal bladder. Counseling should be provided to parents but, due to a favorable outcome, termination of the pregnancy is no longer recommended. Management is primarily surgical, with the main aims of obtaining secure abdominal wall closure, achieving urinary continence with preservation of renal function, and, finally, adequate cosmetic and functional genital reconstruction. Several methods for bladder reconstruction with creation of an outlet resistance during the newborn period are favored worldwide. Removal of the bladder template with complete urinary diversion to a rectal reservoir can be an alternative. After reconstructive surgery of the bladder, continence rates of about 80% are expected during childhood. Additional surgery might be needed to optimize bladder storage and emptying function. In cases of final reconstruction failure, urinary diversion should be undertaken. In puberty, genital and reproductive function are important issues. Psychosocial and psychosexual outcome depend on long-term multidisciplinary care to facilitate an adequate quality of life.
PMID 19878548
http://www.ojrd.com/content/4/1/23
Critical windows of exposure for children's health: the reproductive system in animals and humans
Environ Health Perspect. 2000 Jun;108 Suppl 3:491-503.
Pryor JL, Hughes C, Foster W, Hales BF, Robaire B.
University of Minnesota Medical School, Minneapolis, Minnesota, USA. Abstract Drugs and environmental chemicals can adversely affect the reproductive system. Currently, available data indicate that the consequences of exposure depend on the nature of the chemical, its target, and the timing of exposure relative to critical windows in development of the reproductive system. The reproductive system is designed to produce gametes in far greater excess than would seem to be necessary for the survival of species. Ten to hundreds of millions of spermatozoa are generated daily by most adult male mammals, yet very few of these germ cells succeed in transmitting their genetic material to the next generation. Although the number of oocytes produced in mammalian females is more limited, and their production occurs only during fetal life, most ovaries contain several orders of magnitude more oocytes than ever will be fertilized. Toxicant exposures may affect critical events in the development of the reproductive system, ranging from early primordial germ cell determination to gonadal differentiation, gametogenesis, external genitalia, or signaling events regulating sexual behavior. Although there are differences between the human reproductive system and that of the usual animal models, such models have been extremely useful in assessing risks for key human reproductive and developmental processes. The objectives for future studies should include the elucidation of the specific cellular and molecular targets of known toxicants; the design of a systematic approach to the identification of reproductive toxicants; and the development of sensitive, specific, and predictive animal models, minimally invasive surrogate markers, or in vitro tests to assess reproductive system function during embryonic, postnatal, and adult life.
PMID 10852849
2007
Polycystic ovary syndrome and its developmental origins
Rev Endocr Metab Disord. 2007 Jun;8(2):127-41.
Dumesic DA, Abbott DH, Padmanabhan V. Source Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA. danieldumesic@aol.com
Abstract
The prenatal testosterone (T)-treated adult female rhesus monkey is one animal model of polycystic ovary syndrome (PCOS) in women, with early prenatal T excess programming a permanent PCOS-like phenotype characterized by luteinizing hormone (LH) hypersecretion from reduced hypothalamic sensitivity to steroid negative feedback and relative insulin excess from increased abdominal adiposity. These combined reproductive and metabolic abnormalities are associated with ovarian hyperandrogenism and follicular arrest in adulthood, as well as premature follicle differentiation and impaired embryo development during gonadotropin therapy for in vitro fertilization (IVF). A second animal model for PCOS, the prenatal T-treated sheep also is characterized by LH hypersecretion from reduced hypothalamic sensitivity to steroid negative feedback, persistent follicles and insulin resistance, but also is associated with intrauterine growth retardation and compensatory growth after birth. The ability of prenatal T excess in both species to alter the developmental trajectory of multiple organ systems in utero provides evidence that the hormonal environment of intrauterine life programs target tissue differentiation, raising the possibility that T excess in human fetal development promotes PCOS in adulthood. Such a hypothesis must include data from clinical studies of PCOS women to clarify the homology between these PCOS-like animal models and PCOS per se in reproductive and metabolic function. Future studies should develop new clinical strategies that improve pregnancy outcome and minimize pregnancy loss in women with disorders of insulin action, including PCOS, obesity and diabetes mellitus as well as minimize transgenerational susceptibility to adult PCOS and its metabolic derangements in male close relatives.
PMID 17659447
Age-specific changes in sex steroid biosynthesis and sex development
Best Pract Res Clin Endocrinol Metab. 2007 Sep;21(3):393-401.
Krone N, Hanley NA, Arlt W.
Source
Division of Medical Sciences, Institute of Biomedical Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Abstract
Normal male sex development requires the SRY gene on the Y chromosome, the regression of Müllerian structures via anti-Müllerian hormone (AMH) signalling, the development of the Wolffian duct system into normal male internal genital structures consequent to testosterone secretion by the testicular Leydig cells, and finally, sufficient activation of testosterone to dihydrotestosterone by 5alpha-reductase. All these events take place during weeks 8-12 of gestation, a narrow window of sexual differentiation. Recent studies in human fetal development have demonstrated the early fetal expression of the adrenocorticotrophic hormone (ACTH) receptor and all steroidogenic components necessary for the biosynthesis of cortisol. These findings provide compelling evidence for the assumed pathogenesis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, diminished feedback to the pituitary due to glucocorticoid deficiency, subsequent ACTH excess, and up-regulation of adrenal androgen production with subsequent virilization. Another CAH variant, P450 oxidoreductase deficiency, manifests with 46,XX disorder of sex development (DSD), i.e., virilized female genitalia, despite concurrently low circulating androgens. This CAH variant illustrates the existence of an alternative pathway toward the biosynthesis of active androgens in humans which is active in human fetal life only. Thus CAH teaches important lessons from nature, providing privileged insights into the window of human sexual differentiation, and particularly highlighting the importance of steroidogenesis in the process of human sexual differentiation.
PMID 17875487
