Born sex refers to the biological characteristics that classify individuals as male, female, or intersex, determined around the time of conception. It encompasses observable biological features such as chromosomes, gonads, and internal and external anatomy. This biological definition is distinct from gender identity, which is a person’s internal sense of self. Understanding biological sex involves exploring genetic instructions and developmental processes.
Chromosomal Determination
Biological sex is primarily established at conception by the combination of sex chromosomes inherited from parents. Human cells contain 46 chromosomes, with two designated as sex chromosomes: X and Y. An embryo develops as female if it receives two X chromosomes (XX) or as male if it receives one X and one Y chromosome (XY).
The sperm plays a decisive role in this determination, as eggs consistently carry an X chromosome, while sperm can carry either an X or a Y chromosome. The Y chromosome carries the SRY (Sex-determining Region Y) gene. This gene acts as a transcription factor, binding to specific DNA regions and initiating the cascade of events that lead to male development by promoting testis formation from an undifferentiated gonad. The SRY protein induces Sertoli cell differentiation early in XY embryos.
Development of Biological Traits
Chromosomal instructions guide the development of biological sex characteristics during fetal life. During early gestation, around weeks 4 to 6, all fetuses possess undifferentiated gonads, which are bipotential, meaning they can develop into either testes or ovaries. Around the seventh week of gestation, the presence of the SRY gene in XY embryos triggers the differentiation of these indifferent gonads into testes. In XX embryos, without the SRY gene, the undifferentiated gonads develop into ovaries.
Once formed, the gonads begin to produce hormones that direct further sexual differentiation. In males, the fetal testes secrete two hormones: Müllerian inhibiting substance (MIS) and testosterone. MIS causes the regression of the Müllerian ducts, which would otherwise form female internal reproductive organs like the uterus and fallopian tubes. Simultaneously, testosterone stimulates the development of the Wolffian ducts into male internal structures, including the epididymis, vas deferens, and seminal vesicles.
Testosterone is converted by the enzyme 5-alpha-reductase into dihydrotestosterone (DHT, a more potent androgen. DHT is responsible for the masculinization of the external genitalia, leading to the formation of the penis and scrotum from the genital tubercle and labioscrotal folds. In female development, the absence of MIS allows the Müllerian ducts to form the uterus, fallopian tubes, and the upper part of the vagina, while the absence of significant androgen exposure leads to the development of the clitoris and labia from the undifferentiated external structures. The external genitalia begin to differentiate around 11 weeks and are distinguishable by 14 weeks of gestation.
Natural Variations in Development
The process of biological sex development, while following XX-female and XY-male pathways, exhibits a natural spectrum of variations. These are collectively known as variations in sex development (VSDs) or intersex traits. These conditions arise from differences in chromosomal patterns, hormonal signaling, or the body’s response to hormones during fetal development.
One category involves atypical chromosomal patterns, such as individuals with XXY (Klinefelter syndrome) or X0 (Turner syndrome), which can influence internal and external sex organ development, and may affect pubertal progression. Other variations occur even with typical XX or XY chromosomes. For instance, in individuals with 46,XX chromosomes, exposure to excess male hormones before birth, often due to congenital adrenal hyperplasia (CAH), can lead to an enlarged clitoris and fused labia, presenting external genitalia that appear more masculine.
Conversely, individuals with 46,XY chromosomes may have external genitalia that are incompletely formed, ambiguous, or appear female. This can be due to conditions like androgen insensitivity syndrome (AIS), where the body does not fully respond to androgens, or 5-alpha-reductase deficiency, which impairs the conversion of testosterone to DHT. Some individuals may also be born with ovotesticular DSD, possessing both ovarian and testicular tissue, which can result in ambiguous external genitalia. These biological variations show the complexity of sex development and represent natural occurrences within human biology.