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Hormones (Athens, Greece) 2010There have been considerable advances concerning understanding of the early and later stages of ovarian development; a number of genes have been implicated and their... (Review)
Review
There have been considerable advances concerning understanding of the early and later stages of ovarian development; a number of genes have been implicated and their mutations have been associated with developmental abnormalities. The most important genes controlling the initial phase of gonadal development, identical in females and males, are Wilms' tumor suppressor 1 (WT1) and steroidogenic factor 1 (SF1). Four genes are likely to be involved in the subsequent stages of ovarian development (WNT4, DAX1, FOXL2 and RSPO1), but none is yet proven to be the ovarian determining factor. Changes in nomenclature and classification were recently proposed in order to incorporate genetic advances and substitute gender-based diagnostic labels in terminology. The term "disorders of sex development" (DSD) is proposed to substitute the previous term "intersex disorders". Three main categories have been used to describe DSD in the 46,XX individual: 1) disorders of gonadal (ovarian) development: ovotesticular DSD, previously named true hermaphroditism, testicular DSD, previously named XX males, and gonadal dysgenesis; 2) disorders related to androgen excess (congenital adrenal hyperplasia, aromatase deficiency and P450 oxidoreductase deficiency); and 3) other rare disorders. In this mini-review, recent advances concerning development of the genital system in 46,XX individuals and related abnormalities are discussed. Basic embryology of the ovary and molecular pathways determining ovarian development are reviewed, focusing on mutations disrupting normal ovarian development. Disorders of sex development according to the revised nomenclature and classification in 46,XX individuals are summarized, including genetic progress in the field.
Topics: Chromosomes, Human, X; Female; Gene Expression Regulation, Developmental; Genitalia; Genotype; Gonadal Dysgenesis, 46,XX; Humans; Karyotyping; Male; Phenotype; Sex Determination Analysis; Sex Determination Processes; Sexual Development; Terminology as Topic
PubMed: 20688619
DOI: 10.14310/horm.2002.1272 -
International Journal of Urology :... Jan 1997
Review
Topics: Amino Acid Sequence; Animals; Base Sequence; Chromosome Mapping; DNA-Binding Proteins; Genes; Gonadal Dysgenesis; Gonads; Humans; Kruppel-Like Transcription Factors; Molecular Sequence Data; Transcription Factors; X Chromosome; Y Chromosome
PubMed: 9179658
DOI: 10.1111/j.1442-2042.1997.tb00129.x -
Journal of Pediatric and Adolescent... Dec 2018Primary ovarian insufficiency (POI) in adolescents not due to cytotoxic therapy has not been well studied. Causes of POI have been described in adults, but adolescents... (Review)
Review
STUDY OBJECTIVE
Primary ovarian insufficiency (POI) in adolescents not due to cytotoxic therapy has not been well studied. Causes of POI have been described in adults, but adolescents might represent a unique subset necessitating a targeted approach to diagnosis, workup, and treatment. We sought to better characterize adolescent POI through a descriptive multicenter study.
DESIGN
Case series of patients with POI.
SETTING
Six tertiary care institutions.
PARTICIPANTS
Patients presenting from 2007 to 2014 aged 13-21 years diagnosed with noncytotoxic POI, with exclusions for those who received gonadotoxic therapy, with 46XY gonadal dysgenesis, or lack of evidence of hypergonadotropic hypogonadism on chart review.
INTERVENTIONS
Review and data extraction of records identified according to International Classification of Diseases Ninth or Tenth Revision codes.
MAIN OUTCOME MEASURES
Data were analyzed for signs and symptoms, workup, and treatments. Complete workup was on the basis of American College of Obstetricians and Gynecologists guidelines. Characteristics of patients with POI who presented with delayed puberty/primary amenorrhea vs secondary amenorrhea were compared.
RESULTS
One hundred thirty-five records were identified. Those who had received cytotoxic therapy (n = 52), 46XY gonadal dysgenesis (n = 7), or on review did not have POI (n = 19) were excluded. Of 57 remaining cases, 16 were 45X, 2 had galactosemia, and 4 had X-chromosome abnormalities. Most did not undergo full etiologic evaluation. Girls diagnosed after primary amenorrhea/delayed puberty were less symptomatic and more likely to receive an estrogen patch than those diagnosed after secondary amenorrhea.
CONCLUSION
Noncytotoxic POI in adolescents is an uncommon condition with, to our knowledge, only 64 cases in 6 institutions over 7 years. These patients might not undergo complete etiological workup. Aside from 45X, the most common etiologies were X-chromosome abnormalities or galactosemia.
Topics: Adolescent; Amenorrhea; Female; Gonadal Dysgenesis; Humans; Primary Ovarian Insufficiency; Puberty, Delayed; Young Adult
PubMed: 29940314
DOI: 10.1016/j.jpag.2018.06.006 -
Journal of Pediatric and Adolescent... Feb 2020Girls with Turner syndrome with Y-chromosome material (TS + Y) are assumed to have nonfunctional gonads with increased tumor risk, therefore prophylactic gonadectomy...
STUDY OBJECTIVE
Girls with Turner syndrome with Y-chromosome material (TS + Y) are assumed to have nonfunctional gonads with increased tumor risk, therefore prophylactic gonadectomy is recommended at diagnosis. In this study we aimed to determine rates of spontaneous thelarche (ST) and spontaneous menarche (SM), and prevalence of gonadal tumor and malignancy in girls with TS + Y, to further inform discussions about gonadectomy.
DESIGN
Retrospective review of clinical and pathology data.
SETTING
Multicenter study involving 4 United States children's hospitals.
PARTICIPANTS
Patients included those with a genetically proven diagnosis of TS + Y and phenotypically female genitourinary exam.
INTERVENTIONS
Demographic characteristics, pubertal development, and gonadal pathology data were abstracted from clinical records. Data for ST were analyzed for patients aged 13 years and older and SM for patients older than 15 years.
MAIN OUTCOME MEASURES
ST, SM, prevalence of gonadal tumor, and malignancy.
RESULTS
Forty-four patients met inclusion criteria. Nineteen patients were 13 years or older; 8/19 (42%) had ST and reached Tanner stages 2-4 and 2 (11%) had normal ovarian pathology. Nineteen patients were 15 years or older; 2/19 (11%) had SM. Thirty-seven patients underwent gonadectomy; 35 had available pathology results. Gonadoblastoma was identified in 35/7 patients (19%), 1 in situ germ cell neoplasia, and 1 dysgerminoma (3%). One patient with bilateral gonadoblastoma had ST and SM.
CONCLUSION
In this multicenter cohort, 42% of girls with TS + Y entered puberty spontaneously and 11% had SM, supportive of gonadal function. Risk of tumor was similar to previous reports. To achieve informed decision-making, discussions about gonadectomy should incorporate potential for gonadal function and tumor risk.
Topics: Adolescent; Castration; Child; Chromosomes, Human, Y; Disease Progression; Female; Gonadoblastoma; Gonads; Humans; Menarche; Retrospective Studies; Risk Factors; Turner Syndrome
PubMed: 31465855
DOI: 10.1016/j.jpag.2019.08.011 -
Urology Journal Nov 2015A wide variety of environmental chemicals/xenobiotics including phthalates have been shown to cause oxidative stress targeting the endocrine system and cause... (Review)
Review
PURPOSE
A wide variety of environmental chemicals/xenobiotics including phthalates have been shown to cause oxidative stress targeting the endocrine system and cause reproductive anomalies. The present review describes various issues by oxidative stress causing male reproductive dysfunctions. Here in this review, the importance and role of phthalate compounds in male reproductive dysfunction has been well documented.
MATERIALS AND METHODS
One class of environmental endocrine disruptors is phthalates. Phthalate compounds are mostly used as plasticizers, which increase the flexibility, durability, longevity, and etc. of the plastics. Large-scale use of plastic products in our daily life as well as thousands of workers engaged in the manufacture of plastic and plastic products and recycling plastic industry are potentially exposed to these chemicals. Further, general population as well as vulnerable groups i.e. children and pregnant women are also exposed to these chemicals. Phthalates are among wide variety of environmental toxicants capable of compromising male fertility by inducing a state of oxidative stress in the testes. They may also generate reactive oxygen species (ROS) that may affect various physiological and reproductive functions.
RESULTS
The available data points out that phthalate compounds may also induce oxidative stress in the male reproductive organs mainly testis and epididymis. They impair spermatogenic process by inducing oxidative stress and apoptosis in germ cells or target sertoli cells and thereby hamper spermatogenesis. They also impair the Leydig cell function by inducing ROS, thereby decreasing the levels of steroidogenic enzymes.
CONCLUSION
Thus in utero and postnatal exposure to phthalate compounds might lead to decreased sperm count and various other reproductive anomalies in the young male.
Topics: DNA Damage; Endocrine Disruptors; Environmental Exposure; Female; Gonadal Dysgenesis; Humans; Infertility, Male; Leydig Cells; Male; Oxidative Stress; Phthalic Acids; Pregnancy; Prenatal Exposure Delayed Effects; Reproduction; Sperm Count; Spermatogenesis; Testis
PubMed: 26571312
DOI: No ID Found -
The Journal of Sexual Medicine Feb 2022Previous studies have suggested that sexual function may be compromised in women born with differences of sex development (DSD) or early loss of gonadal function.
BACKGROUND
Previous studies have suggested that sexual function may be compromised in women born with differences of sex development (DSD) or early loss of gonadal function.
AIM
To describe sexual function and sexual wellbeing in women with complete androgen insensitivity syndrome (CAIS), complete gonadal dysgenesis (GD) and premature ovarian insufficiency (POI) in relation to gynecological measures and in comparison with unaffected women.
METHODS
A cross sectional study including 20 women with CAIS, 8 women with 46,XY GD, 8 women with 46,XX GD, 21 women with POI, and 62 population-derived controls. Study participants underwent gynecological examination for anatomical measurements and evaluation of tactile sensitivity. They responded to the validated Sexual Activity Log (SAL), Profile of Female Sexual Function (PFSF), and the Personal Distress Scale (PDS).
RESULTS
The women with CAIS, XY GD, XX GD and POI showed overall satisfying sexual function in comparison to unaffected age-matched population female controls with a median of 1 to 2 satisfying sexual episodes per week among both the patients and the controls depending on available partner. Women with CAIS had shorter vagina and smaller clitoris and women with XY GD had a significantly shallower vagina in comparison to controls. Clitoral width was also significantly smaller among women with XX GD compared to controls. However, results showed overall good genital touch sensitivity with no significant differences between groups.
CLINICAL IMPLICATIONS
Women with DSD or POI can be informed on overall satisfactory sexual function and normal genital touch sensitivity.
STRENGTHS & LIMITATIONS
The strength is the use of age-matched population-based controls to these rare conditions of DSD and POI. Limitations are the nonresponder rate of recruited controls, as well as the small groups of women with DSD.
CONCLUSION
Women with differences of sex development or early loss of gonadal function show overall good sexual well-being, however clinicians have to make efforts to optimize caretaking and treatment to ensure good sexual quality of life for all patients. Engberg H, Strandqvist A, Berg E, et al., Sexual Function in Women With Differences of Sex Development or Premature Loss of Gonadal Function. J Sex Med 2022;19:249-256.
Topics: Androgen-Insensitivity Syndrome; Cross-Sectional Studies; Female; Gonadal Dysgenesis, 46,XY; Humans; Male; Quality of Life; Sexual Development
PubMed: 34895859
DOI: 10.1016/j.jsxm.2021.11.003 -
Journal of Pediatric and Adolescent... Oct 2022Infertility is common among individuals with differences in sex development (DSD), and affected individuals and families desire fertility counseling. This survey sought...
OBJECTIVE
Infertility is common among individuals with differences in sex development (DSD), and affected individuals and families desire fertility counseling. This survey sought to assess fertility knowledge and experiences with fertility counseling among DSD specialists for DSD conditions excluding congenital adrenal hyperplasia.
DESIGN, SETTING, PARTICIPANTS, AND MEASURES
A survey was iteratively developed by members of the DSD-Translational Research Network (DSD-TRN) Fertility Preservation Workgroup and disseminated to 5 clinician groups: the DSD-TRN, the Society for Pediatric Psychology DSD Special Interest Group (SIG), the Pediatric Endocrine Society DSD-SIG, the Societies for Pediatric Urology, and the North American Society for Pediatric and Adolescent Gynecology.
RESULTS
Completed surveys (n = 110) were mostly from pediatric urology (40.3%), gynecology (25.4%), and endocrinology (20.9%) specialists. Most (73/108, 67.6%) respondents reported discussing fertility potential. Sixty-seven responded to questions regarding fertility potential. Many participants answered questions about the presence of a uterus in individuals with 46,XY complete gonadal dysgenesis and about the potential for viable oocytes in individuals with 46,XY partial gonadal dysgenesis incorrectly. Comments acknowledged the need for further education on fertility in individuals with DSD.
CONCLUSIONS
Many DSD providers have some knowledge of fertility potential, but knowledge gaps remain. Experts expressed a desire for education and accessible resources to counsel effectively about fertility potential for individuals with DSD.
Topics: Disorders of Sex Development; Female; Fertility Preservation; Gonadal Dysgenesis, 46,XY; Humans; Sexual Development; Testis
PubMed: 35296452
DOI: 10.1016/j.jpag.2022.02.004 -
Molecular Genetics & Genomic Medicine Oct 2020Perrault syndrome (PRLTS4; OMIM# 615300) is a rare autosomal recessive disorder and only a few cases have been reported worldwide. We report a Chinese female...
BACKGROUND
Perrault syndrome (PRLTS4; OMIM# 615300) is a rare autosomal recessive disorder and only a few cases have been reported worldwide. We report a Chinese female characterized by sensorineural hearing loss and premature ovarian insufficiency.
METHODS
We evaluated audiological, endocrine, and ultrasound examinations and examined the genetic causes using whole-exome sequencing. We reviewed the literature to discuss the pathogenesis, genotype-phenotype correlation, treatment, and prevention of PRLTS4.
RESULTS
Bioinformatic analysis revealed compound heterozygous mutations in the LARS2 gene, c.880G>A (p.Glu294Lys), and c.2108T>C (p.Ile703Thr) which is a novel missense mutation, co-segregated in this family. Taken together, the patient was clinically diagnosed as PRLTS4. The literature review showed that the phenotype for PRLTS4 varies widely, but the sensorineural hearing loss, increased gonadotropin levels, and amenorrhea occurred frequently. All reported mutations are highly conserved in mammals based on conservation analysis, and there is a mutation hotspot for PRLTS4.
CONCLUSION
This study expanded the mutation spectrum of LARS2 and is the first report of PRLTS4 in a Chinese family. Genetic testing plays an important role in early diagnosis of syndromic deafness and clinical genetic evaluation is essential to guide prevention.
Topics: Amino Acyl-tRNA Synthetases; Female; Gonadal Dysgenesis, 46,XX; Hearing Loss, Sensorineural; Heterozygote; Humans; Mutation, Missense; Phenotype; Young Adult
PubMed: 32767731
DOI: 10.1002/mgg3.1445 -
Tidsskrift For Den Norske Laegeforening... Feb 2008For 10 - 12 children born with ambiguous genitalia in Norway annually, the sex cannot be decided directly after birth. The condition is now termed "Disorders of Sex... (Review)
Review
BACKGROUND
For 10 - 12 children born with ambiguous genitalia in Norway annually, the sex cannot be decided directly after birth. The condition is now termed "Disorders of Sex Development" (DSD). Severely undervirilised chromosomal and gonadal boys (46,XY DSD) represent the greatest challenge; the sex assignment has traditionally been female. This review focuses on challenges within diagnostics and treatment and provides an update on the scientific basis for sex assignment in 46,XY DSD children.
MATERIAL AND METHODS
The article is based on articles retrieved from Pub Med and own clinical experience.
RESULTS AND INTERPRETATION
During the last decade the scientific basis for sex assignment in children born with ambiguous genitalia has been increasingly questioned. The traditional DSD management has been dominated by the belief that DSD children will develop into the assigned sex regardless of the underlying cause as long as the external genitalia are "normalised" before two years of age. The most severely undervirilised 46,XY DSD children were surgically assigned as females, based on an emphasis of the size and functionality of the phallus being important for later psychosexual development into men. New guidelines for DSD management are now being developed based on recent knowledge about prenatal cerebral exposure to critical sex chromosome genes and hormones that influence foetal brain predisposition for later psychosexual development. Assignment of a sex should be based on a precise diagnosis of the condition's underlying cause and thereby a best possible prediction of future gender identity.
Topics: Disorders of Sex Development; Female; Gender Identity; Gonadal Dysgenesis, 46,XY; Humans; Infant, Newborn; Male; Psychosexual Development; Sex Differentiation
PubMed: 18311202
DOI: No ID Found -
Folia Medica Cracoviensia 2019Monorchism in children can be caused by congenital and acquired conditions, and can potentially influence the hormonal and reproductive function of an individual in the... (Review)
Review
Monorchism in children can be caused by congenital and acquired conditions, and can potentially influence the hormonal and reproductive function of an individual in the long term. Depending on the etiology, different approaches to the solitary testis have been suggested; however, studies on this topic are scarce. Prevention of anorchia is the main goal in the management of a child with monarchism. e risk of bilateral testicular loss must be weighed against the risk of performing surgery on a healthy gonad. Little is known about the long-term consequences of the various methods for fixation of the testis. This paper provides an up-to-date summary of the current literature on congenital and acquired monarchism in childhood.
Topics: Child; Clinical Decision-Making; Gonadal Dysgenesis, 46,XY; Humans; Male; Orchiectomy; Plastic Surgery Procedures; Risk Assessment; Spermatic Cord Torsion; Testicular Neoplasms; Testis; Urogenital Abnormalities
PubMed: 31180081
DOI: No ID Found