Genetic Determination of Sex
The genetic sex of the future child is established exclusively at the moment of fertilization. Normally, a human zygote contains 22 pairs of autosomes and one pair of sex chromosomes. The combination of sex chromosomes predetermines the subsequent development of the reproductive system:
- Female karyotype is designated as 46,XX.
- Male karyotype is designated as 46,XY.
The absolute determinant of male sex is the Y chromosome. A key role in the mechanism of male differentiation is played by the SRY gene, which belongs to the family of specific DNA-regulatory Sox genes. This gene is responsible for encoding the regulatory protein known as TDF (Testis-Determining Factor). Under the direct influence of TDF, initially bipotent (indifferent) gonads begin their transformation and differentiation into male-type gonads (testes).
Embryogenesis of the Reproductive System
The intrauterine development of the reproductive system follows a strict timeline and pattern. Until 45–50 days of embryonic development, the indifferent stage persists. During this period, the gonad primordia are completely identical and lack signs of sex differentiation.
The critical stage occurs at the 8th week of intrauterine development. Further differentiation proceeds via one of two pathways:
- Male development (testicular formation): The process is actively triggered and driven by the TDF regulatory factor and genes of the Sox family.
- Female development (ovarian formation): Occurs as the default pathway in the absence of the aforementioned male regulatory factors.
Once the fetal testes are formed, they begin to produce male sex hormones and the specific müllerian-inhibiting factor (anti-müllerian hormone). The synthesis of these substances dictates the correct differentiation of all remaining structures of the reproductive tract.
True Hermaphroditism
True hermaphroditism is a rare disorder of sex development with specific morphological, genetic, and clinical characteristics. The primary criterion for reliable diagnosis of this condition is the histological detection of both testicular and ovarian tissues in the patient's gonads.
Genetic Picture: In approximately 80% of cases, patients exhibit a 46,XX female karyotype. In other cases, a 46,XY male karyotype or various forms of genetic mosaicism are found.
Clinical Manifestations:
- Virilization: Most patients show significant masculinization of external features, leading them to be raised predominantly as males.
- Gynecomastia: Development of breast tissue along a female phenotype may occur.
- Cyclic hematuria: Patients may experience periodic blood in the urine, which pathophysiologically represents occult uterine bleeding.
Male Pseudohermaproditism
Male pseudohermaproditism is also known in medical literature by the synonyms Klinefelter–Reifenstein–Albright syndrome and testicular feminization syndrome.
From a genetic standpoint, these patients have a normal male genotype of 46,XY. Morphologically, they possess testes, but the clinical picture is characterized by incomplete masculinization. Patients often present with hypospadias, micropenis, and an underdeveloped scrotum, which may or may not contain testes.
Etiology and Pathogenesis: Incomplete development of male features in the presence of testes is associated with androgen dysfunction. Three main causes of the pathology are identified:
- Defects in testosterone synthesis.
- Defects in testosterone metabolism in peripheral tissues.
- Receptor abnormalities — absence or decreased sensitivity of target cells to sex hormone effects.