Yes, individuals can be phenotypically female despite having XY chromosomes. This is typically due to disruptions in the typical male development pathway.
Understanding Sex Determination
Typically, sex determination in humans depends on the presence or absence of the SRY gene, located on the Y chromosome. The SRY gene triggers the development of testes, which then produce testosterone and other hormones leading to the development of male characteristics.
How XY Females Occur
XY females arise when this typical pathway is disrupted. Some possible reasons include:
- SRY Gene Mutation or Deletion: The SRY gene might be mutated or absent from the Y chromosome. Without a functional SRY gene, the testes do not develop, and the default developmental pathway leads to a female phenotype.
- Androgen Insensitivity Syndrome (AIS): In this condition, the individual has a functional SRY gene and produces testosterone. However, their cells are unable to respond to androgens (male hormones) due to a mutation in the androgen receptor gene, located on the X chromosome. This leads to female or partially female external genitalia, even though the individual has XY chromosomes and produces testosterone. AIS can range in severity, from complete androgen insensitivity (CAIS), where the individual has a fully female appearance, to partial androgen insensitivity (PAIS), where the individual might have ambiguous genitalia.
- Mutations in Other Genes Involved in Sexual Development: Several other genes besides SRY are involved in the complex process of sexual development. Mutations in these genes can also lead to XY females.
Implications and Discovery
Often, individuals with XY chromosomes who develop as females are unaware of their chromosomal makeup until puberty, when they might not experience typical pubertal changes, or during investigations for infertility. As the initial reference notes, “Girls born with XY chromosomes are genetically boys but for a variety of reasons – mutations in genes that determine sexual development – the male characteristics are never expressed.”
Conclusion
In summary, XY females exist due to genetic variations that interrupt the typical development of male characteristics, despite the presence of a Y chromosome. Androgen insensitivity syndrome and SRY gene mutations are two of the primary causes.
