This work explores the complexities that can arise in sex development, from normal biological processes to developmental deviations that lead to disorders of sex development. Normal biological sex differentiation is determined by hormonal and genetic factors where the sex chromosomes XY and XX determine the path of the first developmental stages. Pivotal genes such as SRY, SOX9, and WNT4 play crucial roles in gonadal development, where ovaries develop in the absence of the Y chromosome and testicles develop in the presence of it. Hormonal regulation, including testosterone and the anti-Mullerian hormone, affects the further formation of the sex organs and secondary sex characteristics. Gene mutations, hormonal imbalances, or environmental factors can cause deviations in sex development. Disorders of sex development can be classified into three main groups based on the karyotype of the affected individual: Sex chromosomal DSD, 46, XY DSD, and 46, XX DSD. We discuss in detail sex chromosomal deviations such as Klinefelter's and Turner’s syndrome, gonadal deviations such as Swyers syndrome, hormonal deviations such as androgen insensitivity syndrome and 5-alpha reductase deficiency. These conditions can lead to ambiguous sex development, infertility, and medical or psychological challenges. This work also explores psychosocial and environmental factors such as exposure to endocrine disruptors, the mother’s health during pregnancy, and cultural norms that influence gender identit

by a higher need for vitamin D in females during pregnancy and lactation. As there are chromosomal differences between females and males, some X and Y Humans (Homo sapiens, meaning 'thinking man' or 'wise man') are the most abundant and widespread species of primates, characterized by bipedalism, minimal body hair, and large, complex brains enabling the development of advanced technology, culture, and language. Humans are highly social beings and tend to live in complex social structures composed of many cooperating and competing groups, from fa Humans are, like all animals, plants, and fungi, a eukaryotic, and like most animals a diploid species. Each somatic cell has two sets of 23 chromosomes, each set received from one parent; gametes have only one set of chromosomes, which is a mixture of the two parental sets. Among the 23 pairs of chromosomes, there are 22 pairs of autosomes and one pair of sex chromosomes. In humans, sex determination is primarily mediated by the SRY gene located on the Y chromosome. While the typical configuration follows an XY sex-determination system (XX for females, XY for males), the genetic expression of the Sex-determining Region Y protein is the critical factor in initiating male gonadal differentiation. Consequently, individuals may be born with a chromosomal genotype that does not align with their phenotypic sex, a condition often resulting in infertility due to the absence of specific genes required for gametogenesis. Genes and environment influence human biological variation in visible characteristics, physiology, disease susceptibility and mental abilities. The exact influence of genes and environment on certain traits is not well understood. While no humans – not even monozygotic twins – are genetically identical, two humans on average will have a genetic similarity of 99.5%-99.9%. This makes them more homogeneous than other great apes, including chimpanzees. This small variation in human DNA compared to many other species suggests a population bottleneck during the Late Pleistocene (around 100,000 years ago), in which the human population was reduced to a small number of breeding pairs. The forces of natural selection have continued to operate on human populations, with evidence that certain regions of the genome display directional selection in the past 15,000 years. In 1984, the US government began to plan the human genome project (HGP), which officially started in 1990. Utilizing the data from the HGP, 92% of the human genome was first sequenced in 2001. After the HGP was completed in April 2003, the All of Us Research Program in 2022 released its first major dataset which included nearly 100,000 whole genome sequences. By April 2023, approximately 245,000… Ther…

The biological differences between males and females encompass different sex chromosomes and differing sex hormones. These differences contribute to sex differences in the development of disease. Typical examples are the higher prevalence of non-reproductive cancers in males, and the higher prevalence of auto-immunity in females. Another example are the sex differences in cardiovascular diseases driven by atherosclerosis. Despite the differences in atherosclerosis in which females develop more often stable plaques as compared to males with more unstable plaques, we lack knowledge about female biology in atherosclerosis. This is because the majority of biomedical research has been performed in male patients, male animals, and male cells. Using a systematic review, we show that sex stratification is scarce in cardiovascular epigenetics. Next, we determined how sex influenced gene regulation by integrating DNA methylation and RNA-sequencing data of the atherosclerotic plaque. The sex differential genes suggest that smooth muscle cells in the plaque are heavily subject to sex differences as underlined by deconvolution analyses, regulatory linkage, RNA-sequencing and single-cell RNA-sequencing. Systems biology approaches have been successfully used to find novel disease targets, such as for coronary artery disease. However, these studies also mainly use predominantly male populations. We generated sex-specific gene regulatory networks of atherosclerosis and determined that female

Abstract The brain presents various structural and functional sex differences, for which multiple factors are attributed: genetic, epigenetic, metabolic, and hormonal. While biological sex is determined by both sex chromosomes and sex hormones, little is known about how these two factors interact to establish this dimorphism. Sex differences in the brain also affect its resident immune cells, microglia, which actively survey the brain parenchyma and interact with sex hormones throughout life. However, microglial differences in density and distribution, morphology and ultrastructural patterns in physiological conditions during adulthood are largely unknown. Here, we investigated these aforementioned properties of microglia using the Four Core Genotypes (FCG) model, which allows for an independent assessment of gonadal hormones and sex chromosomal effects in four conditions: FCG XX and Tg XY− (both ovaries); Tg XX Sry and Tg XY Sry (both testes). We also compared the FCG results with XX and XY wild-type (WT) mice. In adult mice, we focused our investigation on the ventral hippocampus across different layers: CA1 stratum radiatum (Rad) and CA1 stratum lacunosum-moleculare (LMol), as well as the dentate gyrus polymorphic layer (PoDG). Double immunostaining for Iba1 and TMEM119 revealed that microglial density is influenced by both sex chromosomes and sex hormones. We show in the Rad and LMol that microglia are denser in FCG XX compared to Tg XY Sry mice, however, microglia were d

number of chromosomes normal in the tissue cells of the animal to which it belongs, but of these half belong to the female gamete and are derived from