scholarly journals Specific morphogenetic events in mouse external genitalia sex differentiation are responsive/dependent upon androgens and/or estrogens

2012 ◽  
Vol 84 (3) ◽  
pp. 269-279 ◽  
Author(s):  
Esequiel Rodriguez ◽  
Dana A. Weiss ◽  
Max Ferretti ◽  
Hong Wang ◽  
Julia Menshenia ◽  
...  
Keyword(s):  
Sex Differentiation ◽  
External Genitalia

scholarly journals Minipuberty: Looking Back to Understand Moving Forward

2021 ◽  
Vol 8 ◽  
Author(s):  
Laura Lucaccioni ◽  
Viola Trevisani ◽  
Alessandra Boncompagni ◽  
Lucia Marrozzini ◽  
Alberto Berardi ◽  
...  
Keyword(s):  
Crucial Role ◽  
Linear Growth ◽  
Sex Differentiation ◽  
External Genitalia ◽  
Complete Suppression ◽  
Fetal Life ◽  
Hpg Axis ◽  
Health And Disease ◽  
Males And Females ◽  
Related Pattern

Hypothalamic-pituitary-gonadal (HPG) axis activation occurs three times in life: the first is during fetal life, and has a crucial role in sex determination, the second time is during the first postnatal months of life, and the third is with the onset of puberty. These windows of activation recall the three windows of the “Developmental Origin of Health and Disease” (DOHaD) paradigm and may play a substantial role in several aspects of human development, such as growth, behavior, and neurodevelopment. From the second trimester of pregnancy there is a peak in gonadotropin levels, followed by a decrease toward term and complete suppression at birth. This is due to the negative feedback of placental estrogens. Studies have shown that in this prenatal HPG axis activation, gonadotropin levels display a sex-related pattern which plays a crucial role in sex differentiation of internal and external genitalia. Soon after birth, there is a new increase in LH, FSH, and sex hormone concentrations, both in males and females, due to HPG re-activation. This postnatal activation is known as “minipuberty.” The HPG axis activity in infancy demonstrates a pulsatile pattern with hormone levels similar to those of true puberty. We review the studies on the changes of these hormones in infancy and their influence on several aspects of future development, from linear growth to fertility and neurobehavior.

scholarly journals Prenatal low-dose methyltestosterone, but not dihydrotestosterone, treatment induces penile formation in female mice and guinea pigs†

2020 ◽  
Vol 102 (6) ◽  
pp. 1248-1260
Author(s):  
Shanshan Wang ◽  
John Lawless ◽  
Zhengui Zheng
Keyword(s):  
Guinea Pigs ◽  
Low Dose ◽  
Androgen Receptors ◽  
Nuclear Translocation ◽  
Sex Differentiation ◽  
External Genitalia ◽  
Gene Expressions ◽  
Female Mice ◽  
Genital Tubercle

Abstract Genital tubercle has bisexual potential before sex differentiation. Females exposed to androgen during sex differentiation show masculinized external genitalia, but the effects of different androgens on tubular urethral and penile formation in females are mostly unknown. In this study, we compared the masculinization effects of commonly used androgens methyltestosterone, dihydrotestosterone, and testosterone on the induction of penile formation in females. Our results suggested that prenatal treatment with low doses of methyltestosterone, but not same doses of dihydrotestosterone or testosterone, could induce penile formation in female mice. The minimum dose of dihydrotestosterone and testosterone for inducing tubular urethral formation in female mice was, respectively, 50 and 20 times higher than that of methyltestosterone. In vivo methyltestosterone treatment induced more nuclear translocation of androgen receptors in genital tubercles of female mice, affected Wnt signaling gene expressions, and then led to similar patterns of cell proliferation and death in developing genital tubercles to those of control males. We further revealed that low-dose methyltestosterone, but not same dose of dihydrotestosterone or testosterone, treatment induced penile formation in female guinea pigs. Exposure of female mouse genital tubercle organ culture to methyltestosterone, dihydrotestosterone, or testosterone could induce nuclear translocation of androgen receptors, suggesting that the differential effect of the three androgens in vivo might be due to the hormonal profile in mother or fetus, rather than the local genital tissue. To understand the differential role of these androgens in masculinization process involved is fundamental to androgen replacement therapy for diseases related to external genital masculinization.

THE TESTIS IN PATIENTS WITH ABNORMALITIES OF SEX DIFFERENTIATION. HISTOLOGY AND ENDOCRINE FUNCTION

1973 ◽  
Vol 73 (1) ◽  
pp. 179-188 ◽  
Author(s):  
R. Sandrini Neto ◽  
M. A. Rivarola ◽  
R. Coco ◽  
C. Bergadá
Keyword(s):  
Sexual Differentiation ◽  
Normal Values ◽  
Sex Differentiation ◽  
External Genitalia ◽  
Poor Response ◽  
Testicular Tissue ◽  
Endocrine Function ◽  
Plasma Testosterone ◽  
Before And After ◽  
Female External Genitalia

ABSTRACT Testicular function was studied in 18 patients with abnormalities of sexual differentiation. Fourteen patients were prepubertal and four postpubertal. Plasma testosterone was determined before and after 5000 IU HCG administered daily during 5' days. Of the fourteen prepubertal patients, the two true hermaphrodites and the patient with asymmetrical gonadal differentiation showed a poor response to gonadotrophin stimulation. This could be explained by the small amount of active testicular tissue or its coexistence with ovarian and rudimentary gonadal tissue which might exert some influence on the endocrine function of the testis. In the group of eight patients with male pseudo-hermaphroditism and ambiguous external genitalia, the response to HCG showed a large variation. The three patients with small testes had lowest values i. e. 210, 198 and 192 ng/100 ml. The remaining five patients showed normal values ranging between 360 and 720 ng/100 ml. The ambiguous external genitalia of these patients could be explained as being due to a diminished androgen target organ sensitivity limited to the external genitalia. The three prepubertal patients with male pseudo-hermaphroditism and female external genitalia showed a marked increase in plasma testosterone with HCG ranging between 598 and 1100 ng/100 ml. The four pubertal cases also had high values in basal conditions, between 920 and 1870, which increased even more after gonadotrophin stimulation, in one case from 1382 to 2264 ng/100 ml. This hypersensitivity to exogenous HCG, even in infancy, correlates with the elevated basal values observed in adult patients with otherwise female external genitalia and androgen insensitivity. Finally, the HCG stimulation test could be useful for the demonstration of testicular tissue in prepubertal patient with abnormalities of sexual differentiation, although it cannot be used as a prognosis of masculinization or feminization at puberty.

scholarly journals Penile Embryology and Anatomy

2010 ◽  
Vol 10 ◽  
pp. 1174-1179 ◽  
Author(s):  
Jenny H. Yiee ◽  
Laurence S. Baskin
Keyword(s):  
Sex Differentiation ◽  
External Genitalia ◽  
Venous Drainage ◽  
Testicular Development ◽  
Erectile Tissue ◽  
Corpora Cavernosa ◽  
Dorsal Vein ◽  
Skin Sensation ◽  
Pediatric Urologist ◽  
Dorsal Nerves

Knowledge of penile embryology and anatomy is essential to any pediatric urologist in order to fully understand and treat congenital anomalies. Sex differentiation of the external genitalia occurs between the 7thand 17thweeks of gestation. The Y chromosome initiates male differentiation through the SRY gene, which triggers testicular development. Under the influence of androgens produced by the testes, external genitalia then develop into the penis and scrotum. Dorsal nerves supply penile skin sensation and lie within Buck's fascia. These nerves are notably absent at the 12 o'clock position. Perineal nerves supply skin sensation to the ventral shaft skin and frenulum. Cavernosal nerves lie within the corpora cavernosa and are responsible for sexual function. Paired cavernosal, dorsal, and bulbourethral arteries have extensive anastomotic connections. During erection, the cavernosal artery causes engorgement of the cavernosa, while the deep dorsal artery leads to glans enlargement. The majority of venous drainage occurs through a single, deep dorsal vein into which multiple emissary veins from the corpora and circumflex veins from the spongiosum drain. The corpora cavernosa and spongiosum are all made of spongy erectile tissue. Buck's fascia circumferentially envelops all three structures, splitting into two leaves ventrally at the spongiosum. The male urethra is composed of six parts: bladder neck, prostatic, membranous, bulbous, penile, and fossa navicularis. The urethra receives its blood supply from both proximal and distal directions.

scholarly journals Socio-medical burden of managing a Nigerian child with 46XY male disorder of sex differentiation: A Case Report

2019 ◽  
Vol 5 (2) ◽  
pp. 280-286
Author(s):  
OO Oba-Daini ◽  
MB Fetuga ◽  
IO Ogundele ◽  
CC Nwokoro ◽  
AA Olatunji ◽  
...  
Keyword(s):  
Leydig Cells ◽  
Sex Differentiation ◽  
Phenotypic Expression ◽  
External Genitalia ◽  
Ambiguous Genitalia ◽  
Resource Poor Setting ◽  
Social Challenges ◽  
Nigerian Child ◽  
Medical Burden ◽  
Bipotential Gonad

Phenotypic expression of the male internal and external genitalia is due largely to the interplay between the proper differentiation of the bipotential gonad, the production of testosterone from the Leydig cells and the response of the undifferentiated external genitalia to Dihydrotestosterone. When any of the pathways involved in the mechanisms described above are distorted, it results in the 46 XY Disorder of Sex Differentiation (DSD).The incidence of 46 XY DSD ranges from 20 to 41% among the cases of Disorder of Sex Differentiation (DSD) in Nigeria, though there is a paucity of data on this condition. This report describes an under-virilized genetically male child who presented with ambiguous genitalia in the neonatal period and was subsequently diagnosed as SRY positive 46 XY DSD with reduced testosterone synthesis. This report is necessitated by the need to create awareness and highlight the relevant medico-social challenges in the management of DSD in a resource-poor setting.

scholarly journals Morphology of the external genitalia of the adult male and female mice as an endpoint of sex differentiation

2012 ◽  
Vol 354 (1-2) ◽  
pp. 94-102 ◽  
Author(s):  
Dana A. Weiss ◽  
Esequiel Rodriguez ◽  
Tristan Cunha ◽  
Julia Menshenina ◽  
Dale Barcellos ◽  
...  
Keyword(s):  
Adult Male ◽  
Sex Differentiation ◽  
External Genitalia ◽  
Male And Female ◽  
Female Mice

VARIANTS OF EMBRYONIC TESTICULAR DYSGENESIS: BILATERAL ANORCHIA AND THE SYNDROME OF RUDIMENTARY TESTES

1962 ◽  
Vol 40 (4) ◽  
pp. 521-536 ◽  
Author(s):  
Cesar Bergada ◽  
William W. Cleveland ◽  
Howard W. Jones ◽  
Lawson Wilkins
Keyword(s):  
Leydig Cells ◽  
Sex Differentiation ◽  
Fibrous Tissue ◽  
Adult Life ◽  
External Genitalia ◽  
Female Gender ◽  
Normal Male ◽  
Surgical Exploration ◽  
Adult Age ◽  
Group A

ABSTRACT Three groups of patients, all of whom had chromatin-negative buccal smears are reported. The chromosomes were XY in the 5 cases in which studies were made. Group A (»Syndrome of rudimentary testes«) consisted of 4 patients with exceedingly small rudimentary testes who showed no abnormality of male sex differentiation except for a very minute penis. The testes were composed of scanty, small testicular tubules, containing pre-Sertoli cells and some spermatogonia. Foetal Leydig cells were present. Group B consisted of 4 patients with incompletely masculinized external genitalia and normal male gonaducts but in addition there was persistence of Mullerian elements in all cases, with an infantile uterus in two cases. These findings were similar to those of male pseudohermaphrodites; but careful surgical exploration with extensive microscopic sections revealed no gonadal tissue. Small nodules were present consisting only of fibrous tissue and in three cases a small clump of cells resembling either aberrant adrenal cells or Leydig cells. It is possible that these patients were male pseudohermaphrodites who had had defective testes in early embryonic life which had degenerated later. Group C (»Bilateral Anorchia«) consisted of 4 patients of adolescent or adult age whose sex organs were entirely male. Testes had never been palpated. They failed to develop secondary sexual characteristics at puberty and they grew tall with eunuchoid proportions. Careful surgical exploration revealed no gonads in either the inguinal canals or the abdomen. The vasa deferentia were traced to their ends and were found to end blindly or in rudimentary epidydimes. According to the theory of Jost functioning testes must have been present in the stage of embryonic sex differentiation and degenerated later. The selection of the sex of rearing is discussed and it is pointed out that the patients of Group A and have a phallus so small that they can never function adequately as males. Accordingly it is better that they be assigned the female gender in early infancy. This opinion is confirmed by the fact that two patients of Group who were raised as males and treated with testosterone were psychologically very badly maladjusted and in adult life decided to change to the female role.

GONADAL HISTOLOGY IN PATIENTS WITH MALE PSEUDOHERMAPHRODITISM AND ATYPICAL GONADAL DYSGENESIS: RELATION TO THEORIES OF SEX DIFFERENTIATION

1962 ◽  
Vol 40 (4) ◽  
pp. 493-520 ◽  
Author(s):  
Cesar Bergada ◽  
William W. Cleveland ◽  
Howard W. Jones ◽  
Lawson Wilkins
Keyword(s):  
Gonadal Dysgenesis ◽  
Sex Differentiation ◽  
External Genitalia ◽  
The Other ◽  
Male Pseudohermaphroditism ◽  
Chromosomal Mosaicism ◽  
Normal Male ◽  
Turner's Syndrome ◽  
Turner’S Syndrome ◽  
Gonadal Histology

ABSTRACT The anatomic findings and gonadal histology of 41 patients who had atypical forms of gonadal dysgenesis or of male pseudohermaphroditism are described. Fourteen of these cases were classified as atypical gonadal dysgenesis because there were gross evidences of abnormal gonadal development, differing from those of classical Turner's syndrome. In this group there was no incidence of familial inheritance but there were evidences of chromosomal aberrations. Two patients diagnosed as »gonadal dysplasia« had primitive genital streaks differing from those of typical gonadal aplasia (Turner's Syndrome) only in the presence of masses of Leydig-like cells. That this condition is a variant of gonadal aplasia is suggested by the association of short stature in one case and by the demonstration in the other case of chromosomal mosaicism of XO/XX pattern, with the XO cell type predominant as in chromatin-negative Turner's Syndrome. Ten patients had »asymmetrical gonadal differentiation« with a testis on one side and on the other side either no gonad (2 cases), a primitive genital streak (6 cases) or an undifferentiated gonad (2 cases). Among these mosaicism of XO/XY type was demonstrated in one case and it is suspected that more intensive chromosomal studies in the future may show a high incidence of mosaicism or other chromosomal aberration in this group. In addition 2 cases of true hermaphroditism are described. There were 27 male pseudohermaphrodites who had two testes with no histological evidences of dysgenesis. Eight of these patients had female external genitalia and 19 had genitalia which were ambiguous or resembled the male. In 4 patients of the latter group there were completely developed uterus and Fallopian tubes. Since the testes of all the male hermaphrodites showed good development of the medullary components believed to be responsible for male differentiation, it must be assumed that there was a defect in the biosynthesis of the »male organizing substances« of the foetal testes. Normal male XY chromosomal patterns were found in all of our cases which were studied and have been reported by other workers. The high familial incidence of this disorder suggests that an enzyme defect is transmitted by a mutant gene. In the »syndrome of feminizing testes« the demonstration of oestrogenic manifestations after puberty is further evidence of an abnormality of synthesis of testicular hormones. The correlation of gonadal pathology and the sex differentiation of gonaducts and external genitalia is compatible with the theory of Jost that normal masculinization is dependant upon the production of adequate amounts of masculinizing substances by the foetal testes. Discordances between the degree of masculinization (or feminization) of the gonaducts and the external genitalia can be explained only by postulating that there are at least two substances concerned; one causing masculinization of the Wolffian ducts and external genitalia and the other causing disappearance of the Mullerian ducts.

scholarly journals Sexual fate of murine external genitalia development: Conserved transcriptional competency for male-biased genes in both sexes

2021 ◽  
Vol 118 (23) ◽  
pp. e2024067118
Author(s):  
Daiki Kajioka ◽  
Kentaro Suzuki ◽  
Shoko Matsushita ◽  
Shinjiro Hino ◽  
Tetsuya Sato ◽  
...  
Keyword(s):  
Genetic Manipulation ◽  
Sex Differentiation ◽  
External Genitalia ◽  
Independent Manner ◽  
Specificity Protein 1 ◽  
Androgenic Regulation ◽  
Genomic Environment ◽  
Endocrine Factor ◽  
Male Specific ◽  
Specificity Protein

Testicular androgen is a master endocrine factor in the establishment of external genital sex differences. The degree of androgenic exposure during development is well known to determine the fate of external genitalia on a spectrum of female- to male-specific phenotypes. However, the mechanisms of androgenic regulation underlying sex differentiation are poorly defined. Here, we show that the genomic environment for the expression of male-biased genes is conserved to acquire androgen responsiveness in both sexes. Histone H3 at lysine 27 acetylation (H3K27ac) and H3K4 monomethylation (H3K4me1) are enriched at the enhancer of male-biased genes in an androgen-independent manner. Specificity protein 1 (Sp1), acting as a collaborative transcription factor of androgen receptor, regulates H3K27ac enrichment to establish conserved transcriptional competency for male-biased genes in both sexes. Genetic manipulation of MafB, a key regulator of male-specific differentiation, and Sp1 regulatory MafB enhancer elements disrupts male-type urethral differentiation. Altogether, these findings demonstrate conservation of androgen responsiveness in both sexes, providing insights into the regulatory mechanisms underlying sexual fate during external genitalia development.

ABNORMALITIES OF SEX DIFFERENTIATION

PEDIATRICS ◽  
1960 ◽  
Vol 26 (5) ◽  
pp. 846-857
Author(s):  
Lawson Wilkins
Keyword(s):  
Gender Role ◽  
Early Life ◽  
Gonadal Dysgenesis ◽  
Sex Differentiation ◽  
External Genitalia ◽  
Later Life ◽  
Exploratory Laparotomy ◽  
Male Pseudohermaphroditism ◽  
True Hermaphroditism ◽  
Positive Pattern

There are many discordances between the anatomic development of the external and internal sex organs, the chromosomal patterns, the gonadal morphology and the secondary sexual development. The psychosexual orientation is not predetermined by any of these, but depends largely upon the gender role assigned to a child in early life. It is, therefore, most important to select in early life the sex to which the child can best adapt. The abnormalities of sex differentiation are: 1) Gonadal dysgenesis, in which there are various widely differing defects in the embryonic development of the gonads. These conditions are often due to chromosomal aberrations. There is a low familial incidence. 2) Male pseudohermaphroditism, in which testes are morphologically fairly well developed, but have defective secretion of "male organizing substance." 3) Female pseudohermaphroditism, in which masculinization of the external genitalia of females is due to androgens of the fetal adrenals or transmitted from the mothers during pregnancy. Ambiguity of the external genitalia is usually the finding which arouses a suspicion of an abnormality of sex differentiation. However, the finding of firm masses in the groins or labia of apparent females or the absence of gonads in apparent males are also indications for more extensive diagnostic studies. The study of the nuclear chromatin pattern of cells in smears of the buccal mucosa is the most important diagnostic screening test. A chromatin-positive pattern indicates that the patient is either a female pseudohermaphrodite, a true hermaphrodite or a case of "testicular dysgenesis." In chromatin-positive cases the urinary excretion of 17-ketosteroids should be measured to determine whether or not the patient has virilizing adrenal hyperplasia. Patients with a chromatin-negative pattern have either male pseudohermaphroditism, true hermaphroditism or some form of gonadal dysgenesis. Exploratory laparotomy with gonadal biopsies is necessary to establish the diagnosis. When the diagnosis is made in early infancy, all types of female pseudohermaphrodites should be reared as females. In male pseudohermaphroditism the assignment of the gender role depends largely upon the degree of phallic development. In true hermaphroditism one must take into consideration both the anatomy of the external genitalia and the type of development of the gonads. The explanations to be given to the parents and the hazards of changing the gender role in later life are discussed. The relative incidence of the various types of abnormalities of sex differentiation are shown. It is pointed out that among 242 patients of all types, there were only 20 cases in which the assignment of a male role would have been preferred.

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