Abnormalities of sexual differentiation Abnormalities of sexual differentiation are secondary to a disruption of one of the stages of the “cascade” described above: chromosomal anomalies, anomalies of gonad development or discordance between chromosomal sex and hormonal factors. 1.Chromosomal abnormalities The chromosomal abnormalities which affect sexual differentiation are secondary to a process of non-disjunction during gametogenesis or the first cleavages resulting in primary hypogonadism (secretion of gonadotropin, GnRH, by the hypothalamus is normal): ✪ In the male sex, Klinefelter syndrome, 47 XXY in all cells or in mosaics, (1/500 boys) leads to a defect in the production of steroid hormones by Leydig cells. At puberty, the clinical picture is that of a tall adolescent with small testicles and sometimes gynecomastia. The absence maturation of the seminiferous tubes with oligospermia or even azoospermia is most often the cause of infertility. ✪ In the female sex, Turner syndrome, 46 X0 in all the cells or in mosaics, (1/2500 girls) leads to a defect in the development of the gonads. The particular morphology (small size, short and webbed neck and especially cardiovascular malformations) sometimes allows early diagnosis. At puberty, ovarian anomalies explain the absence of the first periods. ✪ Other abnormalities in the number of sex chromosomes are rare and have less consequences on the development of the genital system and fertility: 47 XYY, 47 XXX, 48 XXXX. 4) Structural anomalies of sex chromosomes give clinical pictures close to those observed in number anomalies. 2.Abnormalities in gonad development Abnormalities in gonad development can take several forms. “True hermaphroditism”, very rare, is the most complete picture resulting from the coexistence of ovarian and testicular tissue (ovo-testis) or a gonad of each sex. The genital tract is a set of structures derived
from the Wolffian and Müllerian ducts and the external genitalia have an indeterminate appearance. 3.Discordances between chromosomal sex and hormonal secretions Discordances between chromosomal sex and hormonal secretions lead to the occurrence of clinical pictures of sexual ambiguity called “pseudo-hermaphroditisms”. 1)Male pseudo-hermaphroditism, with 46XY karyotype, corresponds to the beginning of testicular development. The secretion of anti-Müllerian hormone, AMH, prevents the development of Mullerian structures; the early secretion of testosterone allows the development of the vas deferens but masculinization does not continue at the level of the urogenital sinus and the external genital organs; this syndrome is rare. ✪ Most often it occurs due to a 5α reductase deficiency which prevents the formation of dihydrotestosterone (DHT), hypospadias of variable severity appears and a lack of masculinization at puberty which depends on the quantity of testosterone secreted. ✪ Sometimes, all the stages of the “cascade” intervene, the DHT secretion is normal but the absence of specific receptors prevents the masculinization of the derivatives of the urogenital sinus and the external genital organs which take on a feminine appearance, this is the so-called “feminizing testicle” syndrome. ✪ More rarely, the lack of testosterone secretion is secondary to an anomaly of its synthesis by enzymatic deficiency which leads to the absence of development of the derivatives of the Wolffian ducts and the urogenital sinus (adnexal glands), the absence of testicular descent and the feminization of the external genital organs. 2) Female pseudo-hermaphroditism, with 46 XX karyotype, is rare. In the absence of testicle and AMH secretion, the genital tract is female (ovaries and uterovaginal canal), masculinization is linked to the abnormally high secretion of androgenic hormones of adrenal origin (adrenal hyperplasia) and results in hypertrophy of the clitoris and fusion of the labioscrotal folds. ✪ Appendices Glossary
✪ regression: Progressive reduction of a structure embryonic during development. ✪ remainder: Residual structure of an embryonic primordium after it has regressed or differentiated.