Sexual dimorphism is associated not only with somatic and behavioral differences between men and women, but also with physiological differences reflected in organ metabolism. Genes regulated by sex hormones differ in expression in various tissues, which is especially important in the case of liver metabolism, with the liver being a target organ for sex hormones as its cells express estrogen receptors (ERs: ERα, also known as ESR1 or NR3A; ERβ; GPER (G protein-coupled ER, also known as GPR 30)) and the androgen receptor (AR) in both men and women. Differences in sex hormone levels and sex hormone-specific gene expression are mentioned as some of the main variations in causes of the incidence of hepatic diseases; for example, hepatocellular carcinoma (HCC) is more common in men, while women have an increased risk of autoimmune liver disease and show more acute liver failure symptoms in alcoholic liver disease. In non-alcoholic fatty liver disease (NAFLD), the distinction is less pronounced, but increased incidences are suggested among men and postmenopausal women, probably due to an increased tendency towards visceral fat accumulation.

Neuroinflammation is one of the postulated mechanisms for Pb neurotoxicity. However, the exact molecular mechanisms responsible for its pro-inflammatory effect are not fully elucidated. In this study, we examined the role of glial cells in neuroinflammation induced by Pb exposure. We investigated how microglia, a type of glial cell, responded to the changes caused by perinatal exposure to Pb by measuring the expression of Iba1 at the mRNA and protein levels. To assess the state of microglia, we analyzed the mRNA levels of specific markers associated with the cytotoxic M1 phenotype (Il1b, Il6, and Tnfa) and the cytoprotective M2 phenotype (Arg1, Chi3l1, Mrc1, Fcgr1a, Sphk1, and Tgfb1). Additionally, we measured the concentration of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). To assess the reactivity and functionality status of astrocytes, we analyzed the GFAP (mRNA expression and protein concentration) as well as glutamine synthase (GS) protein level and activity. Using an electron microscope, we assessed ultrastructural abnormalities in the examined brain structures (forebrain cortex, cerebellum, and hippocampus). In addition, we measured the mRNA levels of Cxcl1 and Cxcl2, and their receptor, Cxcr2. Our data showed that perinatal exposure to Pb at low doses affected both microglia and astrocyte cells’ status (their mobilization, activation, function, and changes in gene expression profile) in a brain-structure-specific manner. The results suggest that both microglia and astrocytes represent a potential target for Pb neurotoxicity, thus being key mediators of neuroinflammation and further neuropathology evoked by Pb poisoning during perinatal brain development.