Gonadal dysgenesis is classified as any
congenital developmental disorder of the reproductive system
in the male or female. It is the atypical development of the
gonads
A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sperm ...
in an
embryo
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...
,
with reproductive tissue replaced with functionless,
fibrous tissue
Fiber or fibre (from la, fibra, links=no) is a natural or artificial substance that is significantly longer than it is wide. Fibers are often used in the manufacture of other materials. The strongest engineering materials often incorporate ...
, termed streak gonads.
Streak gonads are a form of
aplasia
Aplasia (; from Greek ''a'', "not", "no" + ''plasis'', "formation") is a birth defect where an organ or tissue is wholly or largely absent. It is caused by a defect in a developmental process.
Aplastic anemia is the failure of the body to produ ...
, resulting in hormonal failure that manifests as sexual infantism and
infertility
Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects). It is the normal state ...
, with no initiation of
puberty
Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a boy. ...
and
secondary sex characteristics
Secondary sex characteristics are features that appear during puberty in humans, and at sexual maturity in other animals. These characteristics are particularly evident in the sexually dimorphic phenotypic traits that distinguish the sexes of a sp ...
.
Gonadal development is a genetically controlled process by the chromosomal sex (
XX or
XY) which directs the formation of the gonad (
ovary
The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. ...
or
testis
A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testostero ...
).
Differentiation of the gonads requires a tightly regulated cascade of genetic, molecular and morphogenic events.
At the formation of the developed gonad,
steroid
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
production influences local and distant receptors for continued
morphological and
biochemical
Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology an ...
changes.
This results in the appropriate
phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
corresponding to the
karyotype
A karyotype is the general appearance of the complete set of metaphase chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is disce ...
(46,XX for females and 46,XY for males).
Gonadal dysgenesis arises from the failure of signalling in this tightly regulated process during early
foetal development
Prenatal development () includes the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal deve ...
.
Manifestations of gonadal dysgenesis are dependent on the
aetiology
Etiology (pronounced ; alternatively: aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek (''aitiología'') "giving a reason for" (, ''aitía'', "cause"); and ('' -logía''). More completely, e ...
and severity of the underlying defect.
Causes
* Pure gonadal dysgenesis 46,XX also known as
XX gonadal dysgenesis
* Pure gonadal dysgenesis 46,XY also known as
XY gonadal dysgenesis
*
also known as partial gonadal dysgenesis, and
45,X/46,XY mosaicism
45,X/46,XY mosaicism, also known as X0/XY mosaicism and mixed gonadal dysgenesis,
*
Turner syndrome
Turner syndrome (TS), also known as 45,X, or 45,X0, is a genetic condition in which a female is partially or completely missing an X chromosome. Signs and symptoms vary among those affected. Often, a short and webbed neck, low-set ears, low hair ...
also known as
45,X
Turner syndrome (TS), also known as 45,X, or 45,X0, is a genetic condition in which a female is partially or completely missing an X chromosome. Signs and symptoms vary among those affected. Often, a short and webbed neck, low-set ears, low hairl ...
or 45,X0
*
Endocrine disruptions
Pathogenesis
46,XX gonadal dysgenesis
46,XX gonadal dysgenesis is characteristic of
female hypogonadism with a
karyotype
A karyotype is the general appearance of the complete set of metaphase chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is disce ...
of 46,XX.
Streak ovaries
Gonadal dysgenesis is classified as any congenital developmental disorder of the reproductive system
in the male or female. It is the atypical development of the gonads in an embryo,
with reproductive tissue replaced with functionless, fibrous ti ...
are present with non-functional tissues unable to produce the required sex steroid
oestrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal activ ...
.
Low levels of oestrogen effect the
HPG axis HPG may refer to:
* Huppuguda railway station, in Hyderabad, India
* Hypothalamic–pituitary–gonadal axis
* People's Defence Forces (Kurdish: '), the armed wing of the Kurdistan Workers' Party
* Shennongjia Hongping Airport, in Hubei, China
* ...
with no
feedback
Feedback occurs when outputs of a system are routed back as inputs as part of a chain of cause-and-effect that forms a circuit or loop. The system can then be said to ''feed back'' into itself. The notion of cause-and-effect has to be handled ...
to the
anterior pituitary
A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the p ...
to inhibit the secretion of
FSH and
LH.
FSH and LH are secreted at abnormal elevated levels.
Improper levels of these hormones will cause a failure to initiate
puberty
Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a boy. ...
, undergo
menarche
Menarche ( ; ) is the first menstrual cycle, or first menstrual bleeding, in female humans. From both social and medical perspectives, it is often considered the central event of female puberty, as it signals the possibility of fertility.
Gir ...
, and develop
secondary sex characteristics
Secondary sex characteristics are features that appear during puberty in humans, and at sexual maturity in other animals. These characteristics are particularly evident in the sexually dimorphic phenotypic traits that distinguish the sexes of a sp ...
.
If sufficient functional ovarian tissue is present, limited
menstrual cycles
The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...
can occur.
The pathogenesis of 46,XX gonadal dysgenesis is unclear, as it can manifest from a variety of dysregulations.
Interruption during ovarian development in
embryogenesis
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...
can cause 46,XX gonadal dysgenesis with cases of abnormalities in the
FSH receptor
The follicle-stimulating hormone receptor or FSH receptor (FSHR) is a transmembrane receptor that interacts with the follicle-stimulating hormone (FSH) and represents a G protein-coupled receptor (GPCR). Its activation is necessary for the hormo ...
and
mutations
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
in
steroidogenic acute regulatory protein
The steroidogenic acute regulatory protein, commonly referred to as StAR (STARD1), is a transport protein that regulates cholesterol transfer within the mitochondria, which is the rate-limiting step in the production of steroid hormones. It is p ...
(StAR protein) which regulates
steroid hormone
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Wi ...
production.
46,XY gonadal dysgenesis
46,XY gonadal dysgenesis is characteristic of
male hypogonadism
Hypogonadism means diminished functional activity of the gonads—the testes or the ovaries—that may result in diminished production of sex hormones. Low androgen (e.g., testosterone) levels are referred to as hypoandrogenism and low estrogen ...
with
karyotype
A karyotype is the general appearance of the complete set of metaphase chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is disce ...
46,XY.
In
embryogenesis
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...
, the development of the male gonads is controlled by the
testis determining factor
Sex-determining region Y protein (SRY), or Testis-determining factor (TDF), is a DNA-binding protein (also known as gene-regulatory protein/transcription factor) encoded by the ''SRY'' gene that is responsible for the initiation of male sex de ...
located on the sex-determining region of the Y chromosome (
SRY).
The male gonad is dependent on SRY and the
signalling pathways
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately re ...
initiated to several other genes to facilitate
testis
A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testostero ...
development.
The
aetiology
Etiology (pronounced ; alternatively: aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek (''aitiología'') "giving a reason for" (, ''aitía'', "cause"); and ('' -logía''). More completely, e ...
of 46,XY gonadal dysgenesis can be caused by mutations in the
genes
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
involved in testis development such as SRY,
SOX9
Transcription factor SOX-9 is a protein that in humans is encoded by the ''SOX9'' gene.
Function
SOX-9 recognizes the sequence CCTTGAG along with other members of the HMG-box class DNA-binding proteins. It is expressed by proliferating but no ...
,
WT1
Wilms tumor protein (WT33) is a protein that in humans is encoded by the ''WT1'' gene on chromosome 11p.
Function
This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline / glutamine-rich ...
,
SF1, and
DHH.
If a single or combination of these genes are mutated or deleted,
downstream signalling is disrupted, leading to malformation of
male external genitalia
A sex organ (or reproductive organ) is any part of an animal or plant that is involved in sexual reproduction. The reproductive organs together constitute the reproductive system. In animals, the testis in the male, and the ovary in the female, ...
.
SRY acts on gene SOX9 which drives
Sertoli cell
Sertoli cells are a type of sustentacular "nurse" cell found in human testes which contribute to the process of spermatogenesis (the production of sperm) as a structural component of the seminiferous tubules. They are activated by follicle-stimul ...
formation and testis differentiation.
An absence in SRY causes SOX9 to not be expressed at the appropriate time or concentration, leading to a deficiency in
testosterone
Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
and
anti-Müllerian hormone
Anti-Müllerian hormone (AMH), also known as Müllerian-inhibiting hormone (MIH), is a glycoprotein hormone structurally related to inhibin and activin from the transforming growth factor beta superfamily, whose key roles are in growth differen ...
production.
Inadequate levels of testosterone and anti-Müllerian hormone disrupts the development of
Wolffian ducts
The mesonephric duct (also known as the Wolffian duct, archinephric duct, Leydig's duct or nephric duct) is a paired organ that forms during the embryonic development of humans and other mammals and gives rise to male reproductive organs.
Struct ...
and internal genitalia that are key to
male reproductive tract development.
The lack of the male associated steroid hormones drives
Müllerian duct
Paramesonephric ducts (or Müllerian ducts) are paired ducts of the embryo that run down the lateral sides of the genital ridge and terminate at the sinus tubercle in the primitive urogenital sinus. In the female, they will develop to form the fal ...
development and promotes the development of
female genitalia
A sex organ (or reproductive organ) is any part of an animal or plant that is involved in sexual reproduction. The reproductive organs together constitute the reproductive system. In animals, the testis in the male, and the ovary in the female, a ...
.
Gonadal streaks replace the tissues of the testes, resembling
ovarian stroma absent of
follicles.
46,XY gonadal dysgenesis can remain unsuspected until delayed pubertal development is observed.
Approximately 15% of cases of 46,XY gonadal dysgenesis carry ''de novo'' mutations in the SRY gene,
with an unknown causation for the remaining portion of 46,XY gonadal dysgenesis patients.
Mixed gonadal dysgenesis
Mixed gonadal dysgenesis, also known as
X0/XY mosaicism or partial gonadal dysgenesis,
is a sex development disorder associated with sex chromosome
aneuploidy
Aneuploidy is the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46. It does not include a difference of one or more complete sets of chromosomes. A cell with any ...
and mosaicism of the
Y chromosome
The Y chromosome is one of two sex chromosomes (allosomes) in therian mammals, including humans, and many other animals. The other is the X chromosome. Y is normally the sex-determining chromosome in many species, since it is the presence or abse ...
.
Mixed gonadal dysgenesis is the presence of two or more
germ line
In biology and genetics, the germline is the population of a multicellular organism's cells that pass on their genetic material to the progeny (offspring). In other words, they are the cells that form the egg, sperm and the fertilised egg. They ...
cells.
The degree of development of the male reproductive tract is determined by the ratio of germ line cells expressing the XY genotype.
Manifestations of
are highly variable with
asymmetry
Asymmetry is the absence of, or a violation of, symmetry (the property of an object being invariant to a transformation, such as reflection). Symmetry is an important property of both physical and abstract systems and it may be displayed in pre ...
in
gonadal development of testis and streak gonad, accounted for by the percentage of cells expressing XY genotype.
The
dysgenic testis can have adequate functional tissue to produce satisfactory levels of testosterone to cause
masculinisation.
Mixed gonadal dysgenesis is poorly understood at the molecular level.
The loss of the
Y chromosome
The Y chromosome is one of two sex chromosomes (allosomes) in therian mammals, including humans, and many other animals. The other is the X chromosome. Y is normally the sex-determining chromosome in many species, since it is the presence or abse ...
can occur from
deletions,
translocations
In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal-, and Robertsonian translocation. Reciprocal translo ...
, or
migration
Migration, migratory, or migrate may refer to: Human migration
* Human migration, physical movement by humans from one region to another
** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...
failure of paired chromosomes during
cell division
Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...
.
The chromosomal loss results in partial expression of the SRY gene, giving rise to abnormal development of the
reproductive tract
The reproductive system of an organism, also known as the genital system, is the biological system made up of all the anatomical sex organs, organs involved in sexual reproduction. Many non-living substances such as fluids, hormones, and pherom ...
and altered hormone levels.
Turner syndrome
Turner syndrome
Turner syndrome (TS), also known as 45,X, or 45,X0, is a genetic condition in which a female is partially or completely missing an X chromosome. Signs and symptoms vary among those affected. Often, a short and webbed neck, low-set ears, low hair ...
, also known as 45,X or 45,X0, is a
chromosomal abnormality
A chromosomal abnormality, chromosomal anomaly, chromosomal aberration, chromosomal mutation, or chromosomal disorder, is a missing, extra, or irregular portion of chromosomal DNA. These can occur in the form of numerical abnormalities, where ther ...
characterised by a partial or completely missing second
X chromosome
The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex-d ...
,
giving a chromosomal count of 45, instead of the typical count of 46 chromosomes.
Dysregulation in
meiosis
Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately resu ...
signalling to
germ cells
Germ or germs may refer to:
Science
* Germ (microorganism), an informal word for a pathogen
* Germ cell, cell that gives rise to the gametes of an organism that reproduces sexually
* Germ layer, a primary layer of cells that forms during embr ...
during embryogenesis may result in
nondisjunction
Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division (mitosis/meiosis). There are three forms of nondisjunction: failure of a pair of homologous chromosomes to separate in meiosis I ...
and
monosomy X from separation failure of chromosomes in either the parental
gamete
A gamete (; , ultimately ) is a haploid cell that fuses with another haploid cell during fertilization in organisms that reproduce sexually. Gametes are an organism's reproductive cells, also referred to as sex cells. In species that produce t ...
or during early
embryonic divisions.
The
aetiology
Etiology (pronounced ; alternatively: aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek (''aitiología'') "giving a reason for" (, ''aitía'', "cause"); and ('' -logía''). More completely, e ...
of Turner syndrome
phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
can be the result of
haploinsufficiency
Haploinsufficiency in genetics describes a model of dominant gene action in diploid organisms, in which a single copy of the wild-type allele at a locus in heterozygous combination with a variant allele is insufficient to produce the wild-type ...
, where a portion of critical genes are rendered inactive during embryogenesis.
Normal
ovarian development requires these vital regions of the X chromosome that are inactivated.
Clinical manifestation include
primary amenorrhea
Amenorrhea is the absence of a menstrual period in a woman of reproductive age. Physiological states of amenorrhoea are seen, most commonly, during pregnancy and lactation (breastfeeding). Outside the reproductive years, there is absence of menses ...
,
hypergonadotropic hypogonadism
Hypergonadotropic hypogonadism (HH), also known as primary or peripheral/gonadal hypogonadism or primary gonadal failure, is a condition which is characterized by hypogonadism which is due to an impaired response of the gonads to the gonadotropin ...
, streak gonads,
infertility
Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects). It is the normal state ...
, and failure to develop
secondary sex characteristics
Secondary sex characteristics are features that appear during puberty in humans, and at sexual maturity in other animals. These characteristics are particularly evident in the sexually dimorphic phenotypic traits that distinguish the sexes of a sp ...
.
Turner syndrome is not diagnosed until a delayed onset of
puberty
Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a boy. ...
with
Müllerian structures found to be in infantile stage.
Physical
phenotypic
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
characteristics include
short stature
Short stature refers to a height of a human which is below typical. Whether a person is considered short depends on the context. Because of the lack of preciseness, there is often disagreement about the degree of shortness that should be called '' ...
,
dysmorphic
A dysmorphic feature is an abnormal difference in body structure. It can be an isolated finding in an otherwise normal individual, or it can be related to a congenital disorder, Genetics, genetic syndrome or birth defect. Dysmorphology is the stud ...
features and
lymphedema
Lymphedema, also known as lymphoedema and lymphatic edema, is a condition of localized swelling caused by a compromised lymphatic system. The lymphatic system functions as a critical portion of the body's immune system and returns interstitial fl ...
at birth.
Comorbidities
In medicine, comorbidity - from Latin morbus ("sickness"), co ("together"), -ity (as if - several sicknesses together) - is the presence of one or more additional conditions often co-occurring (that is, concomitant or concurrent) with a primary c ...
include
heart defects
A congenital heart defect (CHD), also known as a congenital heart anomaly and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascular ...
,
vision
Vision, Visions, or The Vision may refer to:
Perception Optical perception
* Visual perception, the sense of sight
* Visual system, the physical mechanism of eyesight
* Computer vision, a field dealing with how computers can be made to gain un ...
and
hearing problems
Hearing loss is a partial or total inability to hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to acquire spoken l ...
,
diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
, and low
thyroid hormone
File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4
rect 376 268 820 433 Thyroid-stimulating hormone
rect 411 200 849 266 Thyrotropin-releasing hormone
rect 297 168 502 200 Hypothalamus
rect 66 216 386 25 ...
production.
Endocrine disruptions
Endocrine disruptors
Endocrine disruptors, sometimes also referred to as hormonally active agents, endocrine disrupting chemicals, or endocrine disrupting compounds are chemicals that can interfere with endocrine (or hormonal) systems. These disruptions can cause c ...
interfere with the
endocrine system
The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...
and
hormones
A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and beh ...
.
Hormones are critical for the correct events in embryogenesis to occur.
Foetal development
Prenatal development () includes the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal deve ...
relies on the proper timing of the delivery of hormones for
cellular differentiation
Cellular differentiation is the process in which a stem cell alters from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellular ...
and maturation.
Disruptions can cause
sexual development disorders leading to gonadal dysgenesis.
Diagnosis
Management
History
Turner syndrome was first described independently by Otto Ulrich in 1930 and
Henry Turner in 1938.
46,XX pure gonadal dysgenesis was first reported in 1960.
46,XY pure gonadal dysgenesis, also known as Swyer syndrome, was first described by Gim Swyer in 1955.
See also
*
(DoDI) 6130.03, 2018, section 5, 13f and 14m
The (DoDI) 6130.03, 2018, section 5, 13f and 14m is the writing which bars persons with "true hermaphroditism" (ovotesticular disorder of sex development), "pseudohermaphroditism" and "pure gonadal dysgenesis" from serving in the United States A ...
*
Ovotestis
An ovotestis is a gonad with both testicular and ovarian aspects. In humans, ovotestes are an infrequent anatomical variation associated with gonadal dysgenesis. The only mammals where ovotestes are not symptomatic of an intersex variation are mole ...
*
46 XX 46 may refer to:
* 46 (number)
* ''46'' (album), a 1983 album by Kino
* "Forty Six", a song by Karma to Burn from the album ''Appalachian Incantation'', 2010
* One of the years 46 BC, AD 46, 1946
Events January
* January 6 - The 1946 No ...
References
External links
{{DEFAULTSORT:Gonadal Dysgenesis
Congenital disorders of female genital organs
Intersex variations
Rare diseases