The detrimental implications of tobacco smoke on systemic health have been widely established during the past few decades. Nonetheless, increasing evidence has begun to shed more light on the serious impact that smoke exposure could also have on mammal reproductive health in terms of overall ovarian dysfunction and gestation. A variety of these complications seem to be causally related to specific chemical substances contained in cigarette smoke and their possible effects on ovarian tissues and cells, such as granulosa cells. Granulosa cells represent the functional unit of the ovary and are able to establish a bidirectional cross-talk relationship with the oocyte during folliculogenesis, which makes them vital for its correct growth and development. Based on these premises, the current review focuses on the presence of related smoke-induced damages in granulosa cells. Data have been grouped according to the studied tobacco constituents and the molecular pathways involved, in order to synthesize their impact on granulosa cells and fertility. Attention is further brought to the correlation between electronic cigarettes and female reproduction, although there have been no investigations so far regarding e-cigarette-related granulosa cell exposure. We summarize how tobacco constituents are able to cause alterations in the “life” of granulosa cells, ranging from luteal steroidogenesis and follicular loss to granulosa cell apoptosis and activation of the autophagic machinery. Further studies have been conducted to elucidate the relationship between lifestyle and fertility as to reduce the morbidity connected with infertility.

The female reproductive system represents a sensitive target of the harmful effects of cigarette smoke, with folliculogenesis as one of the ovarian processes most affected by this exposure. The aim of this study was to analyze the impact of tobacco smoking on expression of oxidative stress-related genes in cumulus cells (CCs) from smoking and non-smoking women undergoing IVF techniques. Real time PCR technology was used to analyze the gene expression profile of 88 oxidative stress genes enclosed in a 96-well plate array. Statistical significance was assessed by one-way ANOVA. The biological functions and networks/pathways of modulated genes were evidenced by ingenuity pathway analysis software. Promoter methylation analysis was performed by pyrosequencing. Our results showed a down-regulation of 24 genes and an up-regulation of 2 genes (IL6 and SOD2, respectively) involved in defense against oxidative damage, cell cycle regulation, as well as inflammation in CCs from smoking women. IL-6 lower promoter methylation was found in CCs of the smokers group. In conclusion, the disclosed overall downregulation suggests an oxidant-antioxidant imbalance in CCs triggered by cigarette smoking exposure. This evidence adds a piece to the puzzle of the molecular basis of female reproduction and could help underlay the importance of antioxidant treatments for smoking women undergoing IVF protocols.

Female reproduction focuses mainly on achieving fully grown follicles and competent oocytes to be successfully fertilized, as well as on nourishing the developing offspring once pregnancy occurs. Current evidence demonstrates that obesity and/or high-fat diet regimes can perturbate these processes, leading to female infertility and transgenerational disorders. Since the mechanisms and reproductive processes involved are not yet fully clarified, the present review is designed as a systematic and comparative survey of the available literature. The available data demonstrate the adverse influences of obesity on diverse reproductive processes, such as folliculogenesis, oogenesis, and embryo development/implant. The negative reproductive impact may be attributed to a direct action on reproductive somatic and germinal compartments and/or to an indirect influence mediated by the endocrine, metabolic, and immune axis control systems. Overall, the present review highlights the fragmentation of the current information limiting the comprehension of the reproductive impact of a high-fat diet. Based on the incidence and prevalence of obesity in the Western countries, this topic becomes a research challenge to increase self-awareness of dietary reproductive risk to propose solid and rigorous preventive dietary regimes, as well as to develop targeted pharmacological interventions.

Worldwide, infertility affects between 10 and 15% of reproductive-aged couples. Female infertility represents an increasing health issue, principally in developing countries, as the current inclinations of delaying pregnancy beyond 35 years of age significantly decrease fertility rates. Female infertility, commonly imputable to ovulation disorders, can be influenced by several factors, including congenital malformations, hormonal dysfunction, and individual lifestyle choices, such as smoking cigarettes, stress, drug use and physical activity. Moreover, diet-related elements play an important role in the regulation of ovulation. Modern types of diet that encourage a high fat intake exert a particularly negative effect on ovulation, affecting the safety of gametes and the implantation of a healthy embryo. Identifying and understanding the cellular and molecular mechanisms responsible for diet-associated infertility might help clarify the confounding multifaceted elements of infertility and uncover novel, potentially curative treatments. In this view, this systematic revision of literature will summarize the current body of knowledge of the potential effect of high-fat diet (HFD) exposure on oocyte and follicular quality and consequent female reproductive function, with particular reference to molecular mechanisms and pathways. Inflammation, oxidative stress, gene expression and epigenetics represent the main mechanisms associated with mammal folliculogenesis and oogenesis.

Periodontitis is a common inflammatory disease that affects the teeth-supporting tissue and causes bone and tooth loss. Moreover, in a worldwide population, periodontal disease is often associated with cardiovascular diseases. Emerging studies have reported that one of the major pathogens related to periodontitis is Porphyromonas gingivalis (P. gingivalis), which triggers the inflammatory intracellular cascade. Here, we hypothesized a possible protective effect of ascorbic acid (AA) in the restoration of the physiological molecular pathway after exposure to lipopolysaccharide derived from P. gingivalis (LPS-G). In particular, human gingiva-derived mesenchymal stem cells (hGMSCs) and endothelial-differentiated hGMSCs (e-hGMSCs) exposed to LPS-G showed upregulation of p300 and downregulation of DNA methyltransferase 1 (DNMT1), proteins associated with DNA methylation and histone acetylation. The co-treatment of AA and LPS-G showed a physiological expression of p300 and DNMT1 in hGMSCs and e-hGMSCs. Moreover, the inflammatory process triggered by LPS-G was demonstrated by evaluation of reactive oxygen species (ROS) and their intracellular localization. AA exposure re-established the physiological ROS levels. Despite the limitations of in vitro study, these findings collectively expand our knowledge regarding the molecular pathways involved in periodontal disease, and suggest the involvement of epigenetic modifications in the development of periodontitis.

Virilization of gender-incongruent subjects to whom were assigned the female gender at birth (AFAB) is achieved through testosterone administration. Inter-individual differences in the timing and acquisition of phenotypic characteristics, even if the same hormone preparations and regimens are used, are frequently observed. Polymorphisms of sex hormone receptors and methylation of their gene promoters, as well of several imprinted genes as H19, may underlie the differential response to treatment. Thus, the aim of this study was to examine the possible relationship between the CpG methylation profile of the estrogen receptor 2 gene (ESR2) and H19 promoters and their influence on phenotype modifications in a cohort of AFAB people at baseline (T0) and after 6 mo (T6) and 12 mo (T12) of testosterone therapy (testosterone enanthate, 250 mg i.m. every 28 d). A total of 13 AFAB subjects (mean age 29.3 ± 12.6) were recruited. The percentage of methylation of the ESR2 promoter significantly increased at T6 (adj. p = 0.001) and T12 (adj. p = 0.05), while no difference was detected for H19 (p = 0.237). Methylation levels were not associated with androgen receptor (AR)/estrogen receptor beta (ERβ) polymorphisms nor hormone levels at baseline and after six months of treatment. On the other hand, total testosterone level and patient age resulted in being significantly associated with ESR2 methylation after twelve months of treatment. Finally, the difference in ESR2 promoter methylation between T6 and baseline was significantly associated with the number of CA repeats of the ERβ receptor, adjusted vs. all considered variables (R2 = 0.62, adj. R2 = 0.35). No associations were found with CAG repeats of the AR, age, and estradiol and testosterone levels. Despite the small sample size, we can hypothesize that treatment with exogenous testosterone can modify the ESR2 methylation pattern. Our data also indicated that epigenetic changes may be regulated, suggesting that the modulation of estrogen signaling is relevant shortly after the beginning of the treatment up to T6, with no further significant modification at T12. Furthermore, estrogen receptor methylation appears to be associated with the age of the subjects and exogenous testosterone administration, representing a marker of androgenic treatment. Nonetheless, it will be necessary to increase the number of subjects to evaluate how epigenetic regulation might play a relevant role in the modulation of phenotypical changes after testosterone treatment.

Cigarette smoking among women of reproductive age is known to take a toll on systemic health and fertility potential by severely impacting ovarian tissues and cells, such as granulosa and cumulus cells (CCs). The purpose of this study was to determine the potential damage caused by tobacco smoke at a molecular level in the CCs of females who had undergone in vitro fertilization. The level of intracellular damage was determined by estimating the average telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN), as well as the expression profile of telomere maintenance genes TERF1, TERF2, POT1 and microRNAs miR-155, miR-23a and miR-185. Western blotting analysis was performed to detect consequent protein levels of TERF1, TERF2 and POT1. Our results evidenced significantly lower relative TL and mtDNA-CN and a down-regulation pattern for all three described genes and corresponding proteins in the CCs of smokers compared with controls (p < 0.05). No significant differences were found in the miRNAs’ modulation. Combined, our data add another piece to the puzzle of the complex regulatory molecular networks controlling the general effects of tobacco smoke in CCs. This pilot study extends the until now modest number of studies simultaneously investigating the mtDNA-CN and TL pathways in the human CCs of smoking women.

Background:The real impact of genetic factors on personality is still unknown, even if in literature about 50% of variance in personality traits are considered genetically determined. The determination of the genetic variance in personality traits could promote psychological wellbeing and the prevention of psychopathologies, because there are many experimental evidences showing that mental illness is associated to personality. Numerous studies have showed that Catechol-O-methyltransferase (COMT), brain derived neurotrophic factor (BDNF) and serotonin transporter (5-HTT) are genes whose variants are associated with personality traits. This aim of this study is the investigation of the association between personality traits and 5-HTTLPR/rs255315-HTT promoter variant, COMT Val158Met and BDNF Val66Met gene polymorphisms. Methods: The sample was composed by 132 healthy female students. Genomic DNA was extracted from buccal swab, while personality was assessed with Cloninger's Temperament and Character Inventory-Revised (TCI-R). Linear discriminant analysis was used to analyze how personality characteristics can differentiate individuals in re-