The common saying “everyone starts off as a girl” reflects a fascinating aspect of human embryonic development. Before distinct male or female characteristics appear, an embryo’s reproductive structures are undifferentiated. This initial stage holds the potential to develop into either sex, guided by genetic and hormonal events. This article explores the biological processes from these indifferent stages to the formation of distinct male or female anatomies.
The Undifferentiated Beginnings
During the early weeks of human embryonic development, specifically until around the seventh week of gestation, all embryos possess “bipotential” structures. These structures can develop along either a male or female pathway. At this stage, the embryo contains an indifferent gonad, which is the precursor to either testes or ovaries.
Alongside the indifferent gonad, two pairs of ducts are present: the Wolffian ducts and the Müllerian ducts. The Wolffian ducts have the potential to form male internal reproductive organs, such as the epididymis, vas deferens, and seminal vesicles. Conversely, the Müllerian ducts are precursors to female internal reproductive organs, including the fallopian tubes, uterus, and the upper part of the vagina. Both sets of ducts exist in all embryos regardless of their genetic sex, setting the stage for subsequent differentiation.
The Genetic Blueprint for Sex
The embryo’s genetic makeup, specifically its sex chromosomes, determines whether these indifferent structures develop into male or female organs. Most humans have 46 chromosomes in each cell, with two designated as sex chromosomes: XX for typical female development and XY for typical male development. The egg always contributes an X chromosome, while the sperm can contribute either an X or a Y, thereby determining the genetic sex of the offspring at fertilization.
The presence or absence of the Y chromosome is a significant factor in initiating sex differentiation. On the Y chromosome, a specific gene called SRY (Sex-determining Region Y) triggers the development of male gonads, the testes, from the indifferent gonad. In the absence of a functional SRY gene, the indifferent gonad will develop into ovaries.
Hormones and Physical Development
Once the gonads differentiate—either as testes in XY individuals or ovaries in XX individuals—they start producing hormones that orchestrate the further physical development of the reproductive system. In genetically male (XY) embryos, the testes produce two main hormones: testosterone and Anti-Müllerian Hormone (AMH). Testosterone stimulates the Wolffian ducts to develop into the male internal reproductive structures, such as the epididymis and vas deferens. AMH causes the Müllerian ducts to regress, preventing the formation of female internal organs.
In genetically female (XX) embryos, the absence of the SRY gene and, consequently, the lack of testes means no testosterone. Without testosterone, the Wolffian ducts regress. The absence of AMH allows the Müllerian ducts to develop, forming the fallopian tubes, uterus, and upper vagina. Estrogen, produced later by the developing ovaries, also plays a role in the formation of the female reproductive tract and external genitalia.
Variations in Sex Development
Human sex development is a complex process, and while the XX/XY and hormonal pathways describe typical development, variations can occur. These variations, often referred to as Differences in Sex Development (DSDs) or intersex conditions, arise when the genetic, gonadal, or anatomical development does not align neatly with typical male or female presentations. These conditions are natural biological variations, not disorders, and affect an estimated 0.05% to 1.7% of the population.
Causes of DSDs can include differences in chromosome number, such as XXY or XO combinations, or changes in specific genes involved in sex determination. Hormonal factors, such as atypical production or response to sex hormones during development, can also lead to variations in internal or external genitalia.