Males and females differ in their physiology and disease susceptibility. Research over the past few decades has often neglected the sex of cells/animals, or preferentially used only female or (more commonly) male animals. Such practices may have prevented identification of key sex differences that could inform clinical studies, and ultimately, clinical practice. There is, however, increasing pressure from science-policy stakeholders such as the European Commission and NIH to consider both sexes in both fundamental and clinical research.
In recent years, the gastrointestinal (GI) tract has come to the forefront of metabolic research. The GI tract is now recognised as a major source of signals modulating food intake, insulin secretion and energy balance, with profound effects on whole-body physiology. Using Drosophila, a powerful experimental system to explore the genetic underpinnings of physiological processes, we discovered that there are extensive sex differences in gene expression in the adult Drosophila intestine: an organ not previously known to be sexually dimorphic.
We have explored the nature and significance of these sex differences. Using Drosophila fruit flies as an experimental system, we have discovered how the intestine becomes different between the sexes. We have established that every cell type that makes up the intestine knows whether it is male or female both because of its own genetic make up and the hormones that it is exposed to.
Using flies, we have also been able to establish why the intestine needs to be male or female; this is because it needs to engage in communication with the reproductive organs to sustain reproduction.
Using mice, we have been able to establish that these sex differences are reproductive roles are not a fly peculiarity: they are widely applicable and relevant to mammalian systems, and may even impact our own physiology.