Dear Colleagues,

In vertebrates, the differences between sexes are not limited to the sometimes spectacular anatomical dimorphism seen in birds, but also relate to subtle changes in behavior, physiology, metabolic activities, and gene expression. It is therefore not surprising that most human diseases have a different prevalence, age of onset, or severity between women and men. The last few years have seen significant advances in our understanding of the underlying molecular mechanisms of sexual dimorphism in non-reproductive organs. The present issue of IJMS acknowledges these findings by providing in-depth reviews and highlights of some of the most exciting discoveries. Contributions will cover the case of emblematic “men’s diseases” such as cardiac diseases, where novel mechanisms explain female prevalence in certain arrhythmia. We will also read how the same nuclear receptor contributes to sex-dependent bone remodeling in both sexes. Sex-specific hormones are not the sole cause of sexual dimorphism. This particularly relates to fetal maturation of neuroendocrine/brain functions such as the hypothalamic–pituitary axis or microglial differentiation, whose alterations affect puberty onset or increase neurodegenerative diseases, respectively, with a clear difference between the sexes. Recent findings by Garel have highlighted how developing microglia acquire sexually dimorphic transcriptomic/epigenetic signatures that depend primarily on sex chromosomes and impart a remarkable dimorphic response to environmental perturbations. Several contributions in this Issue will describe how sex influences the adrenocortical steroid axis, from adrenal cortex renewal and pathogenesis, to the sexual dimorphism of mineralocorticoid signaling in kidney and the impacts of glucocorticoid excess in brain and behavior. An in-depth knowledge of mechanisms supporting sexual dimorphism is also essential in trying to improve patient care, as the higher mortality of male patients despite the same prevalence of COVID-19 in both men and women (or misdiagnosed in women) cruelly reminds us.

Dr. Antoine Martinez
Dr. Pr Anne Paule Gimenez-Roqueplo
Guest Editors

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• sex difference in diseases
• molecular mechanisms
• endocrine and neuroendocrine function
• rare diseases
• animal models