Adrenal Hyperplasia Virilized Woman

Möns pubis Clitoris Labia minora Labia maiora bladder _ . _ Seminal vesicle

Appendix testes

Appendix epididymis

Enlarged Efferent Ductules

Efferent ductules Epididymis

Ductus deferens

Efferent ductules Epididymis

Ductus deferens

Foreskin Glans penis

Body of penis Ventral aspect of the penis

Scrotal raphe Scrotum

Figure 9-1. (A) The indifferent embryo, with components indicated: gonads, paramesonephric ducts, mesonephric ducts and tubules, phallus, urethral folds, genital swellings. (B) The female reproductive system. In the abscncc of TDF, testosterone, and MIF, the indifferent emhryo will undergo phenotypic differentiation to female structures. Note that the paramesonephric duct is primarily involved in female development. The mesonephric duct and tubules form only vestigial structures in the female. (C) The male reproductive system. In the presence of TDF, testosterone, and MIF, the indifferent embryo will undergo phenotypic differentiation to male structures. Note that the mesonephric duct and tubules are primarily involved in male development. The paramesonephric ducts form only vestigial structures in the male.

Table 9-1

Development of the Adult Female and Male Reproductive Systems'1'

Indifferent Embryo

Adult Female

Adult Male

Gonads

Ovary, primordial follicles, rete ovarii

Testes, seminiferous tubules, tubuli recti, rete testes, Le/dig cells, Sertoli cells

Paramesonephric ducts

Uterine tubes, uterus, cervix and superior third of the vagina1" Hydatid of Morgagni

Appendix testes

Mesonephric ducts

Appendix vesiculosa Duct of Gartner

Epididymis, ductus deferens, seminal vesicles, ejaculatory duct Appendix epididymis

Mesonephric tubules

Epoophoront paroophoron

Efferent ductules Paradidymis

Phallus

Clitoris

Glans and body of the penis

Urethral folds

Labia minora

Ventral aspect of the penis

Genital swellings

Labia majora, mons pubis

Scrotum

*Demi italics indicate vestigial structures.

*The inferior two-thirds of the vagina develops from the vaginal plate of the urogenital sinus (see Chapter 8 III B).

*Demi italics indicate vestigial structures.

*The inferior two-thirds of the vagina develops from the vaginal plate of the urogenital sinus (see Chapter 8 III B).

2. The processus vaginalis forms the tunica vaginalis in the adult male.

III. DEVELOPMENT OF THE PROSTATE GLAND

A. The prostate gland develops from multiple outgrowths of the prostatic urethra.

B. Dihydrotestosterone (DHT) is the main mediator of prostatic growth in males. This is clinically important in benign prostatic hypertrophy because finasteride (a 5a-re-ductase inhibitor) can reduce DHT levels and shrink the prostate gland. In addition, the action of DHT can be blocked by the receptor antagonist called flutamidc.

IV. CLINICAL CORRELATIONS

1. Double uterus with double vagina is a condition where two uteri and two vaginas are present. It results from the complete lack of fusion of the paramesonephric ducts and the sinovaginal bulbs.

2. Bicornuate uterus is a condition where the uterus has two horns entering a common vagina. It results from partial fusion of the paramesonephric ducts.

3. Bicornuate uterus with rudimentary horn is a condition in which only one side of the uterus forms normally. It results from retarded growth of one of the paramesonephric ducts.

4. Atresia of the vagina is a condition in which the vaginal lumen is blocked. It results from failure of the vaginal plate to canalize and form a lumen. When only the inferior part of the vaginal plate fails to canalize, a condition known as imperforate hymen occurs.

5. Absence of uterus and vagina results from the failure of the paramesonephric ducts and the sinovaginal bulbs to develop.

B. Congenital Anomalies

Double uterus and double vagina Bicornuate uterus

Virilized Female

Bicornuate uterus with rudimentary horn Atresja Qf the vag¡na

Figure 9-2. (A) Formation of the uterus and vagina. The paramesonephric ducts fuse in the midline to form the uterovaginal primordium which develops into the uterus, cervix, and superior third of the vagina. The paramesonephric ducts project into the dorsal wall of the urogenital sinus and induce the formation of the sinovaginal bulhs. The sinovaginal bulbs fuse to form the solid vaginal plate which canalizes to form the inferior two thirds of the vagina. (B) Diagram depicting various congenital anomalies of the uterus and vagina. (From Dudek RW, Fix JF: BRS Embryology, 2nd ed. Baltimore. Williams & Wilkins, 1998, p 179.)

Embryology Uterus

Paramesonephric duct

Sinovaginal bulb

Formation of the Uterus and Vagina

Paramesonephric duct

Sinovaginal bulb

Vaginal Plate

Paramesonephric duct

Uterovaginal primordium Vaginal plate

Paramesonephric duct

Uterovaginal primordium Vaginal plate

B. Male

1. Hypospadias (Figure 9-3) occurs when the urethral folds fail to fuse completely, resulting in the external urethral orifice opening onto the ventral surface of the penis. It is generally associated with a poorly developed penis that curves ventrally, known as chordee (Figure 9-3B).

2. Epispadias (Figure 9-3C) occurs when the external urethral orifice opens onto the dorsal surface of the penis. It is generally associated with exstrophy of the bladder.

3. Undescended testes (cryptorchidism; Figure 9-3D) occurs when the testes fail to descend into the scrotum. This normally is evident within 3 months after birth. The undescended testes may be found in the abdominal cavity or in the inguinal canal. Bilateral cryptorchidism results in sterility.

4. Hydrocele of the testes (Figure 9-3E) occurs when a small patency of the processus vaginalis remains so chat peritoneal fluid can flow into the tunica vaginalis, which results in a fluid-filled cyst near the testes.

5. Congenital inguinal hernia occurs when a large patency of the processus vaginalis remains so that a loop of intestine may herniate into the scrotum or labia majora. It is most common in males and is generally associated with cryptorchidism.

C. Other

1. Female pseudointersexuality (Figure 9-4A)

a. This occurs when an individual has only ovarian tissue histologically and mas-culinization of the female external genitalia. These individuals have a 46,XX genotype.

b- The most common cause is congenital adrenal hyperplasia, a condition in which the fetus produces excess androgens (see Chapter 8 V G).

2. Male pseudointersexuality (see Figure 9-4B)

a. This occurs when an individual has only testicular tissue histologically and various stages of stunted development of the male external genitalia. Individuals have a 46,XY genotype.

b. The most common cause is inadequate production of testosterone and MIF by the fetal testes, owing to the following deficiencies:

(1) 5a-Reductase 2 deficiency

(a) Causes. A mutation in the 5a-reductase 2 gene renders 5a-reduc-tase 2 enzyme inactive. Normally, 5a-reductase 2 catalyzes the conversion of testosterone (T) to DHT.

(b) Clinical findings. Underdevelopment of the penis and scrotum (microphallus, hypospadias, and bifid scrotum) and prostate gland is evident. The epididymis, ductus deferens, seminal vesicle, and ejacu-latory duct are normal. These clinical findings have led to the inference that DHT is essential in the development of the penis and scrotum (external genitalia) and prostate gland in the genotypic XY fetus. At puberty, these individuals demonstrate a striking virilization.

(c) Laboratory tests. An increased T:DHT ratio is diagnostic (normal = 5; 5a-reductase 2 deficiency = 20-60).

(2) 17P-Hydroxysteroid dehydrogenase 3 (HSD) deficiency

(a) Causes. A mutation in the 17P HSD 3 gene renders 17(3 HSD 3 enzyme inactive. Normally, 17(3 HSD 3 catalyzes the conversion of androstenedione to testosterone.

Pseudointersexuality

Figure 9-3. (A) Hypospadias with urethral opening on ventral surface (arrow). (B) Chordee. Note that the penis is poorly developed and bowed vcntrally. (C) Epispadias with two urethral openings on the dorsal surface of the penis (anows). (D) Cryptorchidism. Note that the both testes have not descended into the scrotal sac. (E) Bilateral hydrocele. (B and E courtesy of Dr. T. Ernesto Figueroa. All views from Gilbert-Barness ES [edj: Potter's Atlas of Fetal and Infant Pathology. St. Louis, CV Mosby, 1998, p 294.)

Figure 9-3. (A) Hypospadias with urethral opening on ventral surface (arrow). (B) Chordee. Note that the penis is poorly developed and bowed vcntrally. (C) Epispadias with two urethral openings on the dorsal surface of the penis (anows). (D) Cryptorchidism. Note that the both testes have not descended into the scrotal sac. (E) Bilateral hydrocele. (B and E courtesy of Dr. T. Ernesto Figueroa. All views from Gilbert-Barness ES [edj: Potter's Atlas of Fetal and Infant Pathology. St. Louis, CV Mosby, 1998, p 294.)

Clitoris Girl Development

Figure 9-4. (A) A patient (XX genotype) with female pseudointersexuality due to congenital adrenal hyperplasia (see Chapter 8 V G). Masculinization of female external genitalia is apparent with fusion of the labia majora and enlarged clitoris. (B) A patient (XY genotype) with male pseudointersexuality. Stunted development of male external genitalia is apparent. The stunted external genitalia fooled the parents and the physician into thinking that this XY infant was a girl. In fact, this child was raised as a girl (note the pigtails). As this child neared puberty, testosterone levels increased and clitoral enlargement ensued. This alarmed the parents and the child was brought in for clinical evaluation. (C) A patient (XY genotype) with complete androgen insensitiv-ity (CAIS or testicular feminization). Complete feminization of the male external genitalia is apparent. (A, Courtesy of Dr. J. Kitchin, Department of Obstetrics and Gynecology, University of Virginia; from Sadler TW: Langman's Medical Embryology, 7th ed. Baltimore, Williams & Wilkins, 1995, p 305. B, From Warkany J: Congenital Malformations: Notes and Comments. Chicago, Year Book Medical Publishers, 1971, p 337. C, From Jones HW, Scott WW: Hermaphroditism, Genital Anomalies and Related Endocrine Disorders. Baltimore, Williams &. Wilkins, 1958.)

Figure 9-4. (A) A patient (XX genotype) with female pseudointersexuality due to congenital adrenal hyperplasia (see Chapter 8 V G). Masculinization of female external genitalia is apparent with fusion of the labia majora and enlarged clitoris. (B) A patient (XY genotype) with male pseudointersexuality. Stunted development of male external genitalia is apparent. The stunted external genitalia fooled the parents and the physician into thinking that this XY infant was a girl. In fact, this child was raised as a girl (note the pigtails). As this child neared puberty, testosterone levels increased and clitoral enlargement ensued. This alarmed the parents and the child was brought in for clinical evaluation. (C) A patient (XY genotype) with complete androgen insensitiv-ity (CAIS or testicular feminization). Complete feminization of the male external genitalia is apparent. (A, Courtesy of Dr. J. Kitchin, Department of Obstetrics and Gynecology, University of Virginia; from Sadler TW: Langman's Medical Embryology, 7th ed. Baltimore, Williams & Wilkins, 1995, p 305. B, From Warkany J: Congenital Malformations: Notes and Comments. Chicago, Year Book Medical Publishers, 1971, p 337. C, From Jones HW, Scott WW: Hermaphroditism, Genital Anomalies and Related Endocrine Disorders. Baltimore, Williams &. Wilkins, 1958.)

(b) Clinical findings. Underdevelopment of the penis and scrotum (microphallus, hypospadias, and bifid scrotum) and prostate gland is evident. The epididymis, ductus deferens, seminal vesicle, and ejacula-tory duct are normal. The clinical findings in 17(3-HSD deficiency and 5a-reductase 2 deficiency are very similar.

3- Complete androgen insensitivity (CAIS; testicular feminization syndrome; Figure 9 AC)

a. CAIS occurs when a fetus with a 46,XY genotype develops testes and female external genitalia with a rudimentary vagina; uterus and uterine tubes are generally absent. Testes may be found in the labia majora (they are surgically removed to circumvent malignant tumor formation), b- Individuals with this syndrome present as normal-appearing females, and their psychosocial orientation is female despite their genotype. C. The most common cause is a mutation in the androgen receptor (AR) gene that renders AR inactive.

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Responses

  • Michael
    What is clitoral enlargement?
    4 years ago
  • jasper
    Can a completely virilized female ejaculate?
    4 years ago
  • Tomacca
    What does a normal clitoris look like?
    4 years ago
  • mathilda virrankoski
    How growing vagina in chart?
    4 years ago

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