The Ambiguity of Sexual Fate Determination

Dogma tells us that we become females if we have two XX chromosomes and males if we are XY. Dogma also tells us that this bimodal gender specification occurs early in life. Yet reality may not be so simple. My laboratory has investigated the molecular basis of sex determination in a small nematode worm, often thought of as the “E. coli of animal development.” Over the years, we’ve found a network of genes that regulate sexual fate and figured out ways to turn many of them on and off at will. The surprising result is that we can reverse the sexual fate of a tissue even in adults, breaking the dogma that these fates are fixed early in development. Digging deeper, we’ve found genetic ways to create a molecular signature that is intermediate between male and female, even when cells “look” and “act” male or female. What is perhaps most astonishing is that tissues with these intermediate signatures are poised to switch sexual fate upon environmental exposure to specific chemicals. Just a few hours of chemical exposure can flip the sexual switch. We speculate that gender fates may be similarly induced to flip in tissues within humans. Although clearly speculation, the vast genetic variation in the human population coupled with many chemicals in our environment make this possibility seem entirely plausible.