Sex determination is a fundamental biological process that dictates whether an embryo will develop characteristics typically associated with male or female biology. It represents a precise developmental pathway that guides the formation of reproductive organs and other sex-specific features.
The Role of Chromosomes
Human development begins with the genetic blueprint inherited from parents. Sex chromosomes play a foundational role in determining an embryo’s sex. A typical female embryo possesses two X chromosomes (XX), while a typical male embryo has one X and one Y chromosome (XY).
Sex chromosomes are inherited during fertilization. The egg always contributes an X chromosome. Sperm can carry either an X or a Y. An XX embryo develops if sperm contributes an X; an XY embryo develops if sperm contributes a Y. This chromosomal configuration determines subsequent developmental pathways.
The SRY Gene as a Key Regulator
The Sex-determining Region Y (SRY) gene is located on the Y chromosome. This gene acts as a genetic trigger, initiating testis development from undifferentiated gonads. The SRY gene directs the bipotential gonad, which can develop into either an ovary or a testis, towards a testicular fate.
Upon expression, the SRY gene produces a protein influencing other genes involved in testicular development. This causes embryonic gonad cells to differentiate into Sertoli and Leydig cells, characteristic of testes. These cells organize into testicular cords, forming the testes around the seventh week of gestation.
In the absence of the SRY gene, as in XX individuals, the signal for testicular development is absent. Without the SRY protein, undifferentiated gonads develop into ovaries. The SRY gene’s presence or absence dictates the initial direction of gonadal development.
Hormones and Organ Development
Following SRY gene activation and testis formation, these developing gonads produce hormones for sexual differentiation. The embryonic testes produce testosterone and Anti-Müllerian Hormone (AMH). Testosterone, an androgen, stimulates the Wolffian ducts to develop into male internal reproductive organs: the epididymis, vas deferens, and seminal vesicles.
Sertoli cells within the testes secrete AMH (Müllerian-inhibiting substance). AMH causes the regression of Müllerian ducts, which would otherwise develop into female internal reproductive structures (uterus, fallopian tubes, upper vagina). The combined action of testosterone and AMH forms male internal genitalia and suppresses female structures. Later, testosterone converts to dihydrotestosterone (DHT), driving the development of external male genitalia like the penis and scrotum.
In female embryos, the SRY gene is absent, and ovaries develop. Male hormones are not produced. Without testosterone, Wolffian ducts regress. Without AMH, Müllerian ducts persist and differentiate into fallopian tubes, uterus, and upper vagina. The absence of androgens leads to the development of female external genitalia, including the clitoris, labia majora, and labia minora.
Factors Influencing Atypical Development
While typical sex determination pathways are well-defined, variations can arise if these controls are altered. Deviations stem from changes in genetic instructions or the hormonal environment during embryonic development. For instance, an SRY gene mutation can prevent its function, leading to an XY individual developing ovaries and female characteristics despite possessing a Y chromosome.
Chromosomal variations, such as Klinefelter syndrome (XXY) or Turner syndrome (XO), illustrate how deviations from typical chromosome sets influence development. In XXY individuals, the Y chromosome and SRY gene lead to testicular development, though often with reduced function. In contrast, XO individuals, lacking a second sex chromosome, develop ovaries. Disruptions in hormone production or reception, such as testosterone deficiency or androgen insensitivity, can lead to developmental divergence. These factors highlight the balance required for typical sexual differentiation.
—
References
Human sex determination: a review of the molecular mechanisms. Journal of Genetics and Genomics, 2011.
The SRY gene and sex determination. Trends in Endocrinology & Metabolism, 2004.
Sex determination and gonadal development. Nature Reviews Genetics, 2006.
Molecular mechanisms of normal and abnormal sexual development. Endocrine Reviews, 2006.
Androgen action and the sexual differentiation of the brain. Physiology & Behavior, 2002.
Disorders of sex development: a genetic perspective. Clinical Genetics, 2010.