There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

A systematic review of health effects of electronic cigarettes

Extensive evidence suggests that the release of membrane-enclosed compartments, more commonly known as extracellular vesicles (EVs), is a potent newly identified mechanism of cell-to-cell communication both in normal physiology and in pathological conditions. This review presents evidence about the formation and release of different EVs, their definitive markers and cargo content in reproductive physiological processes, and their capacity to convey information between cells through the transfer of functional protein and genetic information to alter phenotype and function of recipient cells associated with reproductive biology. In the male reproductive tract, epididymosomes and prostasomes participate in regulating sperm motility activation, capacitation, and acrosome reaction. In the female reproductive tract, follicular fluid, oviduct/tube, and uterine cavity EVs are considered as vehicles to carry information during oocyte maturation, fertilization, and embryo-maternal crosstalk. EVs via their cargo might be also involved in the triggering, maintenance, and progression of reproductive- and obstetric-related pathologies such as endometriosis, polycystic ovarian syndrome, preeclampsia, gestational diabetes, and erectile dysfunction. In this review, we provide current knowledge on the present and future use of EVs not only as biomarkers, but also as therapeutic targeting agents, mainly as vectors for drug or compound delivery into target cells and tissues.

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Extracellular Vesicles in Human Reproduction in Health and Disease.

The substantial harmful effects of tobacco smoking on fertility and reproduction have become apparent but are not generally appreciated. Tobacco smoke contains more than 4000 kinds of constituents, including nicotine, tar, carbonic monoxide, polycyclic aromatic hydrocarbons, and heavy metals. Because of the complexity of tobacco smoke components, the toxicological mechanism is notably complicated. Most studies have reported reduced semen quality, reproductive hormone system dysfunction and impaired spermatogenesis, sperm maturation, and spermatozoa function in smokers compared with nonsmokers. Underlying these effects, elevated oxidative stress, DNA damage, and cell apoptosis may play important roles collaboratively in the overall effect of tobacco smoking on male fertility. In this review, we strive to focus on both the phenotype of and the molecular mechanism underlying these harmful effects, although current studies regarding the mechanism remain insufficient.

The hazardous effects of tobacco smoking on male fertility.

Starting from a previous experience carried out by the working group “Building and Environmental Hygiene” of the Italian Society of Hygiene and Preventive Medicine (SItI), the aim of the present work is to define new strategic goals for achieving a “Healthy and Salutogenic City”, which will be useful to designers, local governments and public bodies, policy makers, and all professionals working at local health agencies. Ten key points have been formulated: 1. climate change and management of adverse weather events; 2. land consumption, sprawl, and shrinking cities; 3. tactical urbanism and urban resilience; 4. urban comfort, safety, and security perception; 5. strengths and weaknesses of urban green areas and infrastructures; 6. urban solid waste management; 7. housing emergencies in relation to socio-economic and environmental changes; 8. energy aspects and environmental planning at an urban scale; 9. socio-assistance and welfare network at an urban scale: importance of a rational and widespread system; and 10. new forms of living, conscious of coparticipation models and aware of sharing quality objectives. Design strategies, actions, and policies, identified to improve public health and wellbeing, underline that the connection between morphological and functional features of urban context and public health is crucial for contemporary cities and modern societies.

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Healthy Design and Urban Planning Strategies, Actions, and Policy to Achieve Salutogenic Cities

The aim of this experimental study was to evaluate the effects of nicotine on sperm motility and on non-conventional sperm parameters in vitro. Capacitated spermatozoa isolated from 10 normozoospermic, healthy, non-smoker men were evaluated. Spermatozoa were exposed to increasing concentrations of nicotine (0, 1, 10, and 100 ng/ml) for 3 and 24 hours. Progressive motility and the following non-conventional sperm parameters, evaluated by flow cytometry, were assessed: mitochondrial membrane potential, viability, phosphatidylserine externalization, late apoptosis, degree of chromatin compactness, and DNA fragmentation. Nicotine suppressed, in a concentration-dependent manner, sperm progressive motility starting from the lowest concentration used (1 ng/ml). Similarly, it reduced the percentage of viable spermatozoa and increased the number of spermatozoa in late apoptosis, with altered chromatin compactness, or DNA fragmentation already after 3 hours of incubation. These effects were observed at a concentration similar (100 ng/ml) to that found in the seminal plasma of smokers (70 ng/ml), with the exception of the effects on sperm DNA fragmentation whose significant effect was detected also at a lower concentration (10 ng/ml). Nicotine may be regarded as a noxious component of cigarette smoke on the male reproductive function.

https://journals.sagepub.com/doi/pdf/10.1177/039463201302600317

In vitro effects of nicotine on sperm motility and bio-functional flow cytometry sperm parameters.

During the last decades the study of male infertility and the introduction of the assisted reproductive techniques (ARTs) has allowed to understand that normal sperm parameters do not always predict fertilization. Sperm genetic components could play an important role in the early stages of embryonic development. Based on these acquisitions, several epigenetic investigations have been developed on spermatozoa, with the aim of understanding the multifactorial etiology of male infertility and of showing whether embryonic development may be influenced by sperm epigenetic abnormalities. This article reviews the possible epigenetic modifications of spermatozoa and their effects on male fertility, embryonic development and ART outcome. It focuses mainly on sperm DNA methylation, chromatin remodeling, histone modifications and RNAs.

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Epigenetics of Male Fertility: Effects on Assisted Reproductive Techniques.

Lifestyle, cigarette smoking and environmental pollution have a negative impact on male fertility. Therefore, the aim of this study was to evaluate the in-vitro effects of benzo-α-pyrene (BaP) and aryl hydrocarbon receptor (AHR) agonists on motility and bio-functional sperm parameters. We further assessed whether resveratrol (RES), an AHR antagonist and antioxidant molecule, had any protective effect. To accomplish this, 30 normozoospermic, healthy, non-smoker men not exposed to BaP were enrolled. Spermatozoa of 15 men were incubated with increasing concentrations of BaP to evaluate its effect and to establish its dose response. Then, spermatozoa of the 15 other men were incubated with BaP (15 µM/mL), chosen according to the dose-response and/or RES to evaluate its antagonistic effects. The effects of both substances were evaluated after 3 h of incubation on total and progressive sperm motility and on the following bio-functional sperm parameters evaluated by flow cytometry: Degree of chromatin compactness, viability, phosphatidylserine externalization (PS), late apoptosis, mitochondrial membrane potential (MMP), DNA fragmentation, degree of lipoperoxidation (LP), and concentrations of mitochondrial superoxide anion. Benzo-α-pyrene decreased total and progressive sperm motility, impaired chromatin compactness, and increased sperm lipoperoxidation and mitochondrial superoxide anion levels. All these effects were statistically significant at the lowest concentration tested (15 µM/mL) and they were confirmed at the concentration of 45 µM/mL. In turn, RES was able to counteract the detrimental effects of BaP on sperm motility, abnormal chromatin compactness, lipid peroxidation, and mitochondrial superoxide. This study showed that BaP alters sperm motility and bio-functional sperm parameters and that RES exerts a protective effect on BaP-induced sperm damage.

https://www.mdpi.com/2077-0383/8/4/561/pdf

Environment and Male Fertility: Effects of Benzo-α-Pyrene and Resveratrol on Human Sperm Function In Vitro

Reactive oxygen species favor reproductive processes at low concentrations, but damage spermatozoa and decrease their fertilizing capacity at high concentrations. During infection and/or inflammation of the accessory sex glands reactive oxygen species overproduction may occur which, in turn, may negatively impact on sperm motility, sperm DNA fragmentation, and lipid peroxidation. A number of nutraceutical formulations containing antioxidant molecules have been developed to counteract the deleterious effects of the oxidative stress. A recent formulation containing zinc, D-aspartic acid, and coenzyme-Q10 is present in the pharmaceutical market. Based on these premises, the aim of the present study was to evaluate the effects of this combination on spermatozoa in vitro. The study was conducted on 24 men (32.2 ± 5.5 years): 12 normozoospermic men and 12 asthenozoospermic patients. Spermatozoa from each sample were divided into two control aliquots (aliquot A and B) and an aliquot incubated with zinc, D-aspartic acid, and coenzyme-Q10 (aliquot C). After 3 h of incubation, the following parameters were evaluated: progressive motility, number of spermatozoa with progressive motility recovered after swim-up, lipid peroxidation, and DNA fragmentation. Incubation with zinc, D-aspartic acid, and coenzyme-Q10 maintained sperm motility in normozoospermic men (37.7 ± 1.2 % vs. 35.8 ± 2.3 % at time zero) and improved it significantly in asthenozoospermic patients (26.5 ± 1.9 % vs. 18.8 ± 2.0 % at time zero) (p < 0.01). This resulted in a significantly higher (p < 0.01) number of spermatozoa with progressive motility recovered after swim-up in both normozospermic men (4.1 ± 0.9 vs. 3.3 ± 1.0 millions) and asthenozooseprmic patients (3.2 ± 0.8 vs. 1.6 ± 0.5 millions). Finally, a statistically significant lower sperm lipid peroxidation was found after incubation with zinc, D-aspartic acid, and coenzyme-Q10 (p < 0.05) in both normozospermic men (1.0 ± 0.4 % vs. 2.4 ± 0.9 %) and asthenozooseprmic patients (0.2 ± 0.1 % vs. 0.6 ± 0.2 %). No statistically significant effect was observed on sperm DNA fragmentation. This nutraceutical formulation may be indicated in vitro during the separation of the spermatozoa in the assisted reproduction techniques, during which the spermatozoa undergo an increased oxidative stress.

In vitro effects of zinc, D-aspartic acid, and coenzyme-Q10 on sperm function.

Benzo(a)pyrene (BaP) is a carcinogenic polycyclic aromatic hydrocarbon for human tissues. Still today it is not fully investigated if BaP can affect negatively the male fertility through the BaP‑DNA adducts production. In the present study, BaP Tetrol I‑1 (TI‑1) and BaP Tetrol II‑2 (TII‑2) BaP‑DNA adducts were investigated in spermatozoa of a Sicilian male population. Semen samples from 86 volunteers in two eastern Sicilian cities (Regalbuto and Melilli) were collected. The quality of semen was evaluated in all samples according to the World Health Organization (WHO) guidelines. We analyzed BaP‑DNA adducts in extracted sperm cell DNA using the modified high‑performance liquid chromatography‑fluorescence method to detects both Tetrols. Differences between Tetrol levels were assessed by the Wilcoxon signed‑rank test and the Mann‑Whitney U test, as appropriate. Correlation between semen quality parameters and Tetrol concentrations were analyzed using the Spearman's correlation coefficient. Σ(TI‑1+TII‑2) were significantly higher in spermatozoa of volunteers from Regalbuto. Furthermore, a greater dispersion of the levels of adducts was observed in these specimens. TI‑1 adducts were higher than TII‑2 in Melilli samples (95% CI) and TII‑2 were higher than TI‑1 in Regalbuto semen samples (95% CI). A significant inverse correlation between sperm progressive motility and both TI‑1 and TII‑2 adducts was observed. The present study showed that BaP negatively affects male fertility by TI‑1 and TII‑2 DNA‑adduct production. These results suggest that DNA adducts could be used as biomarker to assess BaP exposure by air pollution. Further studies are needed to confirm if these findings could affect male fertility because of the growing impairment of this function observed in recent years.

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Filippo Giacone

Papers

In vitro effects of nicotine on sperm motility and bio-functional flow cytometry sperm parameters.

Epigenetics of Male Fertility: Effects on Assisted Reproductive Techniques.

Environment and Male Fertility: Effects of Benzo-α-Pyrene and Resveratrol on Human Sperm Function In Vitro

In vitro effects of zinc, D-aspartic acid, and coenzyme-Q10 on sperm function.

B(a)P adduct levels and fertility: A cross‑sectional study in a Sicilian population