Sex steroid hormones play important physiological roles in reproductive and nonreproductive tissues, including immune cells. These hormones exert their functions by binding to either specific intracellular receptors that act as ligand-dependent transcription factors or membrane receptors that stimulate several signal transduction pathways. The elevated susceptibility of males to bacterial infections can be related to the usually lower immune responses presented in males as compared to females. This dimorphic sex difference is mainly due to the differential modulation of the immune system by sex steroid hormones through the control of proinflammatory and anti-inflammatory cytokines expression, as well as Toll-like receptors (TLRs) expression and antibody production. Besides, sex hormones can also affect the metabolism, growth, or virulence of pathogenic bacteria. In turn, pathogenic, microbiota, and environmental bacteria are able to metabolize and degrade steroid hormones and their related compounds. All these data suggest that sex steroid hormones play a key role in the modulation of bacterial-host interactions.

Sex differences are important epidemiological factors that impact in the frequency and severity of infectious diseases. A clear sexual dimorphism in bacterial infections has been reported in both humans and animal models. Nevertheless, the molecular mechanisms involved in this gender bias are just starting to be elucidated. In the present article, we aim to review the available data in the literature that report bacterial infections presenting a clear sexual dimorphism, without considering behavioral and social factors. The sexual dimorphism in bacterial infections has been mainly attributed to the differential levels of sex hormones between males and females, as well as to genetic factors. In general, males are more susceptible to gastrointestinal and respiratory bacterial diseases and sepsis, while females are more susceptible to genitourinary tract bacterial infections. However, these incidences depend on the population evaluated, animal model and the bacterial species. Female protection against bacterial infections and the associated complications is assumed to be due to the pro-inflammatory effect of estradiol, while male susceptibility to those infections is associated with the testosterone-mediated immune suppression, probably via their specific receptors. Recent studies indicate that the protective effect of estradiol depends on the estrogen receptor subtype and the specific tissue compartment involved in the bacterial insult, suggesting that tissue-specific expression of particular sex steroid receptors contributes to the susceptibility to bacterial infections. Furthermore, this gender bias also depends on the effects of sex hormones on specific bacterial species. Finally, since a large number of genes related to immune functions are located on the X chromosome, X-linked mosaicism confers a highly polymorphic gene expression program that allows women to respond with a more expanded immune repertoire as compared with men. Notwithstanding there is increasing evidence that confirms the sexual dimorphism in certain bacterial infections and the molecular mechanisms associated, further studies are required to clarify conflicting data and to determine the role of specific hormone receptors involved in the gender bias of bacterial infections, as well as their potential as therapeutic targets.

Background: A complex interaction between cortisol and dehydroepiandrosterone-sulphate (DHEA-S) is crucial in the stress system balance; several studies have reported increased cortisol levels during chronic stress and a weak counter-regulation by DHEA-S. During pregnancy, scarce information about this system is available, although cortisol and DHEA-S play an important role in the initiation and acceleration of labor. We conducted the present study in order to determine both cortisol and DHEA-S levels during the last trimester of pregnancy in patients exhibiting severe anxiety. Methods: Pregnant women during the 3rd trimester of pregnancy were evaluated by using the self-reported version of the Hamilton Anxiety Rating Scale (HARS). According to the scores obtained from the psychometric scale, participants were divided into two groups: 1) patients exhibiting a cutoff score > 15 were considered with severe anxiety (ANX) (n = 101), and control pregnant subjects (CTRL) (n = 44) with a cutoff score < 5. Morning cortisol, DHEA-S and Cortisol/DHEA-S index were measured in all participants. Comparisons between groups were performed; additionally, correlations between clinical variables, biochemical data and HARS were calculated. Results: Cortisol levels were significantly higher in the ANX group (p < 0.001), whereas those of DHEA-S were significantly lower in the same group (p < 0.01) when compared to healthy pregnant subjects. An increased cortisol/DHEA-S index was observed in the ANX group (p < 0.05). A significant association between cortisol and HARS scores (p = 0.03), was observed even after adjusting by gestational weeks (p = 0.004). Conclusions: Our data support that the cortisol/DHEA-S index is higher in pregnant women with high anxiety levels as compared with healthy pregnant women.

Although progesterone is a steroid hormone mainly associated with female reproductive functions, such as uterine receptivity and maintenance of pregnancy, accumulating data have shown its physiological actions to extend to several non-reproductive functions in the central nervous system (CNS) both in males and females. In fact, progesterone is de novo synthesized in specific brain regions by neurons and glial cells and is involved in the regulation of various molecular and cellular processes underlying myelination, neuroprotection, neuromodulation, learning and memory, and mood. Furthermore, progesterone has been reported to be implicated in critical developmental events, such as cell differentiation and neural circuits formation. This view is supported by the increase in progesterone synthesis observed during pregnancy in both the placenta and the fetal brain. In the present review, we will focus on progesterone actions during CNS development.

Several studies indicate that bisphenol A (BPA) and phthalates may have a role in the development of metabolic diseases using different molecular pathways, including epigenetic regulatory mechanisms. However, it is unclear whether exposure to these chemicals modifies serum levels of miRNAs associated with gestational diabetes mellitus (GDM) risk. In the present study, we evaluated the serum levels of miRNAs associated with GDM (miR-9-5p, miR-16-5p, miR-29a-3p and miR-330-3p) and urinary levels of phthalate metabolites (mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP) and mono(2-ethyl hexyl) phthalate (MEHP)) and bisphenol A in GDM patients and women without GDM during the second trimester of gestation. We observed higher levels of miR-9-5p, miR-29a-3p and miR-330-3p in sera of patients with GDM compared to non-diabetic subjects. Phthalates were detected in 97–100% of urine samples, while BPA only in 40%. Urinary MEHP and BPA concentrations were remarkably higher in both study groups compared to previously reported data. Unadjusted MEHP levels and adjusted BPA levels were higher in non-diabetics than in GDM patients (p = 0.03, p = 0.02). We found positive correlations between adjusted urinary MBzP levels and miR-16-5p expression levels (p < 0.05), adjusted MEHP concentrations and miR-29a-3p expression levels (p < 0.05). We also found negative correlations between unadjusted and adjusted MBP concentrations and miR-29a-3p expression levels (p < 0.0001, p < 0.05), unadjusted MiBP concentrations and miR-29a-3p expression levels (p < 0.01). Urinary MEHP levels reflect a striking exposure to di(2-ethylhexyl) phthalate (DEHP) in pregnant Mexican women. This study highlights the need for a regulatory strategy in the manufacture of several items containing endocrine disruptors in order to avoid involuntary ingestion of these compounds in the Mexican population.