Why am I a girl? Why are you a boy? What is the biological impetus of our gender roles and how does it play a role in the rest of our lives? Researchers from the University of Minnesota set out to understand the mechanism controlling whether an animal will become a male or female and they found instead a lifelong struggle at play inside of us all.

According to a recent study published in the journal Developmental Cell, the cells that determine sex continue to perform throughout a person’s life, working to maintain sexual determination and protection against one of the sex cells overpowering and reprogramming a person’s gender.

"DMRT1 in the testis and FOXL2 in the ovary have been identified as key transcription factors responsible for maintaining sexual differentiation. What we asked in this study was how the cells maintain sexual differentiation and why their sex determination requires continuous protection," said Dr. David Zarkower, the study’s lead author and director of the Developmental Biology Center at the University of Minnesota, in a press release.

Sex determination results in the development of sexual characteristics present in the testis, which are the male sex cells, versus the ovotestis, which are the female sex cells. The first major breakthrough in understanding the biological driver of gender was the discovery of sex chromosomes in the early 1900s. Before then, it was believed that the woman determined her offspring’s gender, which is why King Henry VIII found it necessary to marry six times in order to find a wife to give him a male heir to his throne. Very famously, he had his second wife, Anne Boleyn executed, meanwhile, it is in the testis that gender is determined.

Women have two "X" chromosomes and men have an "X" and a "Y." The presence or absence of the "Y" chromosomes determines the gender of your child. Inside the female egg, women have only "Y" chromosomes, but each sperm cell holds an "X" or a "Y," so whichever sperm fertilizes the egg first will dictate the baby’s gender. 

It was thought that the gender battle stopped at egg fertilization, but after researchers found within mice models that the ovaries or testes require maintenance throughout a person’s life, gender transformation is making more sense.

"While RA signaling between cells is absolutely required for sperm production and male fertility, we found that RA also has a dark side,” Zarkower said. “If DMRT1 is not there to act as a guardian of maleness, retinoic acid has the potential to activate genes driving male-to-female transdifferentiation."

Retinoic acid (RA) is supposed to silence genes that are involved in the female sex determination process, ultimately preventing female organs from developing. At the same time, DMRT1 partners with the male sex gene Sox9 to maintain male gender after birth inside the mouse model. For a male, it is the role of three activating genes that are constantly keeping male sex hormones from turning into female sex hormones.

"This shows cell signaling can transform the identities of the very cells that use it from male to female. We think other cell types may also require similar mechanisms allowing them to use critical signaling molecules without becoming reprogrammed," Zarkower said.

Source: Zarkower D, Minkina A, Matson C, et al. DMRT1 Protects Male Gonadal Cells from Retinoid-Dependent Sexual Transdifferentiation. Developmental Cell, 2014.