‘Female’ Is Not The Default Sex

Repost of a 2014 article from my old WordPress blog.

The loose assumption that the ‘female’ is the default sex is frequently presented as a fact of biological science. Laurent Boulanger and a team of researchers recently published a critical discovery that shatters this assumption.

They discovered that FOXL2 and several other genes must be expressed in order to properly initiate female development. Individuals with XY chromosomes develop into males anyway, but in the absence of the aforementioned cluster of genes, so too would those individuals with XX chromosomes. Previous research has shown the role of FOXL2 in ovarian determination / differentiation in vertebrates, regulating adult ovarian function in mammals and reproductive dysfunction in women, so it is not as surprising a finding as one might think.

As usual, important research in the biological sciences will not be reported in mainstream media—or even mainstream academic press—because it goes against politically comfortable narratives.

[EDIT : See article Why There Are Males & Females for a comprehensive enquiry into the origin and evolution of the sexes.]

→ Boulanger L, et al. (2014) FOXL2 is a female sex-determining gene in the goat. Current Biology, 24(4):404–8.

The origin of sex reversal in XX goats homozygous for the polled intersex syndrome (PIS) mutation was unclear because of the complexity of the mutation that affects the transcription of both FOXL2 and several long noncoding RNAs (lncRNAs). Accumulating evidence suggested that FOXL2 could be the sole gene of the PIS locus responsible for XX sex reversal, the lncRNAs being involved in transcriptional regulation of FOXL2. In this study, using zinc-finger nuclease-directed mutagenesis, we generated several fetuses, of which one XX individual bears biallelic mutations of FOXL2. Our analysis demonstrates that FOXL2 loss of function dissociated from loss of lncRNA expression is sufficient to cause an XX female-to-male sex reversal in the goat model and, as in the mouse model, an agenesis of eyelids. Both developmental defects were reproduced in two newborn animals cloned from the XX FOXL2(-/-) fibroblasts. These results therefore identify FOXL2 as a bona fide female sex-determining gene in the goat. They also highlight a stage-dependent role of FOXL2 in the ovary, different between goats and mice, being important for fetal development in the former but for postnatal maintenance in the latter.

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