Table 1 Contributors to sexual dimorphism in humans with XX and XY sex chromosomes including examples of kidney physiology and pathology
XX | XY |
|---|---|
• Two X chromosomes • More severe effects in X-linked recessive disorders such as X-linked dominant hypophosphatemic rickets and Fabry disease [27] | • One X and one Y chromosome • SRY gene on Y chromosome regulates testis development |
X chromosome inactivation [27,28,29]: Silencing of one chromosome from gene expression through histone modification and DNA methylation to balance X- linked gene dosage between sexes | |
• The inactivated X chromosome is not identical in all cells (mosaicism) • Distribution of X inactivation is unequal or shifts over time (skewing) • Genes escape inactivation. Mutation/alterations may lead to kidney disorders such as Alport Syndrome [27, 29, 30], X-linked nephropathy [27], etc | • Ubiquitous Y gene expression • No need for X chromosome inactivation, but a more severe manifestation of Alport Syndrome, if present |
Differential gene expression is dependent on the parent the gene was inherited from. Abnormal imprinting can lead to an increased risk of Wilms tumor and autosomal dominant polycystic kidney disease (sex-independent in rats [32]) | |
• Both maternal and paternal imprinting of X chromosomes | • Only maternal X chromosome imprinting |
Sex steroids[4]: Sex steroid hormones such as estradiol, testosterone, progesterone, luteinizing hormone (LH), and follicular stimulating hormone (FSH) are present in both sexes. Sex steroids influence a variety of signalling pathways, permanently changing cell epigenetics | |
• High estradiol levels after puberty until levels drop drastically at menopause. It is generally accepted that estrogen has a protective effect on kidneys [33,34,35] | • High testosterone peaks at puberty and remains stable with a continuous decline |
• Differences in lifestyle accumulate over lifetime as differences in epigenetics, DNA methylation, histone modification, chromatin architecture, and miRNA expression. For example, a high sodium diet could lead to an increased risk of chronic kidney disease [37] • Due to aging, there is loss of functioning nephrons in the kidney. Differences in aging between sexes are recorded but mechanisms poorly understood | |
• Due to the additional workload for the fetus, there are alterations in glomerular filtration rate, electrolyte and balance during pregnancy |  |
• The increase and decrease of estrogen and progesterone levels during the different phases of the menstrual cycle can lead to change in blood flow and fluid balance, retention of more sodium and loss of iron |  |