Sexual differentiation is the biological process through which an undifferentiated embryo develops sex-specific characteristics. This development begins with chromosomal sex, which guides gonadal formation, dictating the hormonal environment that shapes the final external appearance. For the first several weeks, the embryo possesses the potential to develop along either male or female lines. This early stage is the indifferent period, where external structures are identical regardless of the embryo’s genetic sex.
The Common Precursors
The external genitalia originate from common, undifferentiated structures that form early in the embryonic period. By the fifth to sixth week of gestation, mesenchymal cells migrate to the perineal area, creating three distinct swellings.
The most prominent precursor is the genital tubercle, which forms at the cranial end of the cloacal folds. This tubercle develops into either the glans and shaft of the penis or the clitoris. Flanking the urogenital sinus are the urethral folds, and lateral to these are the larger labioscrotal swellings.
The eventual fate of these folds and swellings—whether they fuse and elongate or remain separate—determines the final appearance of the external genitalia. For several weeks, the sex cannot be distinguished based on these identical external forms.
The Critical Window: Timing and Hormonal Triggers
The point at which visible changes begin marks the end of the indifferent stage and the beginning of morphological sex differentiation. External genitalia differentiation begins around the ninth week of gestation, following the differentiation of the internal ducts and gonads. The deciding factor for which path the common precursors take is the presence or absence of specific androgens produced by the fetal testes.
The hormone responsible for masculinization is Dihydrotestosterone (DHT), a potent derivative of testosterone. DHT is produced when the enzyme 5-alpha-reductase converts circulating testosterone in target tissues, such as the genital tubercle. High local concentrations of DHT stimulate the growth, elongation, and fusion of the indifferent external structures.
The female pathway is considered the default developmental trajectory. In the absence of high levels of androgens, the external structures do not undergo the same degree of growth or fusion. Therefore, female external genitalia development does not require a specific hormonal signal, but rather the failure of the male-promoting signal to materialize.
The Differentiation Pathway: Male External Genitalia
The presence of Dihydrotestosterone drives morphological changes in the common precursors. Beginning around the ninth week, the genital tubercle undergoes rapid growth and elongation, forming the primordial phallus, which becomes the glans and shaft of the penis.
Simultaneously, the urethral folds begin to fuse along the ventral midline of the elongating phallus. This process encloses the urethral groove, creating the tubular penile urethra. Fusion is completed by the twelfth week, with the line of closure remaining visible as the penile raphe in the adult.
The labioscrotal swellings also respond to the DHT signal by migrating toward the midline and fusing. This fusion creates the scrotum, a single structure that will house the testes after they descend. The line of closure forms the scrotal raphe, which is continuous with the penile raphe. These actions result in fully formed male external genitalia by approximately the fourteenth week of gestation.
The Differentiation Pathway: Female External Genitalia
In the absence of high local concentrations of Dihydrotestosterone, the common precursor structures follow the female developmental path. This process involves growth and modification, but it lacks the extensive fusion and elongation characteristic of the male pathway. The female external genitalia are recognizable between the eighth and fifteenth weeks of development, and are fully defined by the twentieth week.
The genital tubercle, lacking the stimulus for rapid growth, enlarges only slightly to form the clitoris. The clitoris does not undergo significant elongation, and its shaft remains relatively short. The urethral folds, which would have fused in the male, remain separate in the female fetus.
These unfused urethral folds then develop into the labia minora, which flank the vestibule of the vagina. The labioscrotal swellings also remain unfused, developing as two distinct, lateral folds. These larger structures form the labia majora, completing the development of the vulva.