Fgf9 and "Sex Reversal"

Jed Bland


Issue 14
May 2001


"Male mice have unexpectedly been found to switch sex if they lack a gene previously linked with lung development" declares the New Scientistof 23, March, 2001 in all seriousness. "It looked like complete sex reversal," says Ornitz. "The male organs had completely regressed" Instead the 'males' had all developed female sex organs."

Apart from the fact that the male sex organs had not regressed - they had never developed - you would think from reading this that the 'females' had follicles with fertile ova all complete with the necessary external genitalia.

Normally researchers are more circumspect in their written accounts, as in the case of Wnt-4 reviewed elsewhere in this journal, than in their off-the-cuff remarks to journalists. Not so Colvin et al. even in the title of their paper: "Male-to-Female Sex Reversal in Mice lacking Fibroblast Growth Factor 9"(1)

The clue is in the last three words. There are around twenty two different Fibroblast Growth Factors and, as their name implies, their role is in the formation of connective tissue throughout the developing individual. Tissues where Fgf9 expression have been detected include "ventricular myocardium, lung pleura, skeletal myoblasts in the early limb bud, spinal cord motor neurons, olfactory bulb, and gut lumenal epithelium. Fgf9 is coexpressed with other Fgf genes in some skeletal myoblasts, in limb apical ectoderm, in craniofacial ectoderm, and in the retina, inner ear, and tooth bud."(2)In addition it is involved in the development of the prostate (3)

In other words it is a fundamental element in the development of many organs, and it comes as no surprise to learn that it is highly conserved, that is, it has a long evolutionary history. Nor that it is involved in the development of the sex organs any more than others. Why, I wonder, do we talk about lung development but sex determination?

The aim of the study was confirm its role in lung development. For this purpose, mice were bred which lacked an active Fgf9. The lungs did not develop and the mice died at, or soon after, birth. The authors did not say what other tissues did not develop, except that, presumably because of the paper by Giri et al, they investigated the prostate, and (to their surprise, according to the New Scientist) discovered that the testes and associated structures were also affected, with considerable variation. Also, without Mullerian Inhibiting Substance, there was a varying development of ovarian and associated tissue.

"Embryos with two fused uteri and with gonads directly inferolateral to the kidney were considered phenotypically female. . . . . Embryos with epididymides and gonads directly adjacent to the bladder were considered phenotypically male." A somewhat artificial definition of the male and female phenotypes, one might think.

This very detailed study is, of course, important in increasing our understanding of male sexual development, though it says little about female development. It is one of hundreds of genetic studies that are being published, to the despair of the archivists who are trying to cope. A large proportion of these are about sexual dimorphism. They disappear in the multitude, to be sought out by specialists. Sex reversal? Hardly! Yet it lends a cachet to attract the attention of the credulous media.

  1. Colvin, J.S., Green, R.P., Schmahl, J.,Capel, B., Ornitz, D., (2001) Male-to-Female Sex Reversal in Mice lacking Fibroblast Growth Factor 9,Cell, Vol 104, 875-889, March, 23, 2001
  2. Colvin JS, Feldman B, Nadeau JH, Goldfarb M, Ornitz DM (1999)Genomic organization and embryonic expression of the mouse fibroblast growth factor 9 gene.Dev Dyn 1999;216:72-88.
  3. Giri D, Ropiquet F, Ittmann M., (1999) FGF9 is an autocrine and paracrine prostatic growth factor expressed by prostatic stromal cells.J Cell Physiol. 1999 Jul;180(1):53-60.
Web page copyright GENDYS Network. Text copyright of the author. Last amended 28.05.01