Additive effect of Bisphenol A and Pefluoro-sulphoctanoic acid exposure at subacute toxic levels, on a murine model of sertoli cell.

Purpose: Endocrine disruptors (EDs) interfere with the endocrine system leading to health consquences and reproductive derangements. Most EDs are environmental pollutants whose risk evaluation is hampered by the simultaneous exposure to a number of chemicals. Here we investigated the possible mechanistic involvement of Sertoli cells, the nurse cell population in the seminiferous tubule, in the reproductive toxicity of Bisphenol A (BPA) and perfluoro-octane sulphonate (PFOS), two acknowledged EDs, at recognized subacute toxic levels.

Lipidomic Profile of Human Sperm Membrane Identifies a Clustering of Lipids Associated with Semen Quality and Function.

Reduced sperm motility and/or count are among the major causes of reduced fertility in men, and sperm membranes play an important role in the spermatogenesis and fertilization processes. However, the impact of sperm lipid composition on male fertility remains under-investigated. The aim of the present study was to perform a lipidomic analysis of human sperm membranes: we performed an untargeted analysis of membrane lipid composition in fertile (N = 33) and infertile subjects (N = 29).

In vitro binding analysis of legacy-linear and new generation-cyclic perfluoro-alkyl substances on sex hormone binding globulin and albumin, suggests low impact on serum hormone kinetics of testosterone.

In humans, serum testosterone (T) is largely bound to the sex hormone binding globulin (SHBG) and human serum albumin (hSA), resulting in a 2-3 % of unbound or "free" active quote (FT). Endocrine-disrupting chemicals, including perfluoro-alkyl substances (PFAS), are recognized to interfere with the hormonal axes, but the possible impact on the FT quote has not been addressed so far. Here we investigated the possible competition of two acknowledged PFAS molecules on T binding to SHBG and hSA.

Legacy perfluoro-alkyl substances impair LDL-cholesterol uptake independently from PCSK9-function.

Perfluoro-alkyl substances (PFAS) are pollutants, whose exposure was associated with altered levels of low-density lipoproteins (LDL) in humans. Here we investigated this clinical outcome in two groups of young male adults residing in areas of respectively low and high environmental exposure to perfluoro-octanoic-acid (PFOA). From the Regional Authority data on pollution areas, 38 not-exposed and 59 exposed age-matched participants were evaluated for serum levels of total cholesterol (Total-Chol), LDL-Chol, high-density lipoprotein cholesterol (HDL-Chol), triglycerides (Tgl) and chromatography quantified PFOA.

Membrane Cholesterol Inhibits Progesterone-Mediated Sperm Function through the Possible Involvement of ABHD2.

Abhydrolase domain containing 2-acylglycerol lipase (ABHD2) was recently claimed as the membrane receptor of progesterone (P4) in sperm cells, mediating cell processes such as sperm chemotaxis and acrosome reaction. Here, we investigated the role of membrane cholesterol (Chol) on ABHD2-mediated human sperm chemotaxis. Human sperm cells were obtained from twelve normozoospemic healthy donors.

Fertility Impairment after Trekking at High Altitude: A Proof of Mechanisms on Redox and Metabolic Seminal Changes.

Many authors described negative but reversible effects of high-altitude hypoxic exposure on animal and human fertility in terms of sperm concentration, function, and biochemical alterations. The aim of this study was to evaluate the acute and chronic effects of high-altitude exposure on classical sperm parameters, redox status, and membrane composition in a group of travellers. Five healthy Italian males, all lowlanders not accustomed to the altitude, were evaluated after 19 days-trekking through low, moderate, and high altitudes in the Himalayas.

Interference of C6O4 on platelet aggregation pathways: Cues on the new-generation of perfluoro-alkyl substance.

Background: Health concerns associated with the exposure to legacy perfluoro-alkyl substances (PFAS) led to the development of new-generation PFAS, such as C6O4. Here we investigated the possible effects of C6O4 on the platelet's activation profile, by incubating human platelets from healthy donors with C6O4 at different concentrations and evaluating the effects on activation, production and phenotype of platelets micro-particles (MPV) and aggregation under-flow. Based on the eventual platelet pro-aggregation profile detected, the preventive effect of acetylsalicylic acid (ASA) was also explored.

Sperm Cholesterol Content Modifies Sperm Function and TRPV1-Mediated Sperm Migration.

Transient receptor potential channels-vanilloid receptor 1 (TRPV1) regulates thermotaxis in sperm-oriented motility. We investigated the role of membrane cholesterol (Chol) on TRPV1-mediated human sperm migration. Semen samples were obtained from five normozoospemic healthy volunteers.

Sperm DNA Methylation at Metabolism-Related Genes in Vegan Subjects.

Objective: To investigate if epigenome of sperm cells could be dynamically affected by nutrition.

Design And Methods: We assessed 40 healthy volunteers with different dietary habits and collected their demographic characteristics, as well as clinical and anthropometric parameters. We compared methylation profiles in sperm quantified by bisulfite pyrosequencing, at promoter-associated CpG sites of genes involved in metabolism including fat mass and obesity-associated () and melanocortin-4 receptor () from six vegans and 34 omnivores.

Endocrine disruption of vitamin D activity by perfluoro-octanoic acid (PFOA).

Perfluoroalkyl substances (PFAS) are a class of compounds used in industry and consumer products. Perfluorooctanoic acid (PFOA) is the predominant form in human samples and has been shown to induce severe health consequences, such as neonatal mortality, neurotoxicity, and immunotoxicity. Toxicological studies indicate that PFAS accumulate in bone tissues and cause altered bone development.

Effects of endocrine disruptors on fetal testis development, male puberty, and transition age.

Purpose: Endocrine disruptors (EDs) are exogenous substances able to impair endocrine system; consequently, they may cause numerous adverse effects. Over the last years, particular focus has been given to their harmful effects on reproductive system, but very little is known, especially in males. The aim of this review is to discuss the detrimental effects of EDs exposure on fetal testis development, male puberty, and transition age.

Testosterone is sequestered in dysfunctional adipose tissue, modifying androgen-responsive genes.

Background/objective: The recognized association between male hypogonadism and obesity has multifactorial implications on adipose tissue (AT) physiology. The fat solubility of testosterone (T) suggests a sequestration process in fat depots, leading to reduced circulating levels of T in obesity. Several evidence suggest that steroids play a two-sided inhibitory role on adipogenesis by locally decreasing lipid accumulation and by stimulating lipolysis.

Increased Cardiovascular Risk Associated with Chemical Sensitivity to Perfluoro-Octanoic Acid: Role of Impaired Platelet Aggregation.

Perfluoro-alkyl substances (PFAS), particularly perfluoro-octanoic acid (PFOA), are persisting environmental chemicals showing bioaccumulation in human tissues. Recently, exposure to PFAS has been associated with increased prevalence of cardiovascular diseases (CVDs). However, a causal role of PFAS in atherosclerosis pathogenesis is under-investigated.

Perfluorooctanoic acid alters progesterone activity in human endometrial cells and induces reproductive alterations in young women.

Female fecundity is finely regulated by hormonal signaling, representing a potential target for endocrine-disrupting chemicals. Among the chemicals of most concern are the perfluoroalkyl substances (PFAS), widely used in consumer goods, that are associated with adverse effects on reproductive health. In this context, the endometrium clearly represents an important fertility determining factor.

Perfluoro-octanoic acid impairs sperm motility through the alteration of plasma membrane.

Context: Perfluoroalkyl-substances (PFAS) are chemical additives considered harmful for humans. We recently showed that accumulation of perfluoro-octanoic acid (PFOA) in human semen of exposed subjects was associated with altered motility parameters of sperm cells, suggesting direct toxicity.

Objectives: To determine whether direct exposure of human spermatozoa to PFOA was associated to impairment of cell function.

Testicular Cancer: Genes, Environment, Hormones.

Testicular cancer (TC) represents one of the most peculiar clinical challenges at present. In fact, currently treatments are so effective ensuring a 5 years disease-free survival rate in nearly 95% of patients. On the other hand however, TC represents the most frequent newly diagnosed form of cancer in men between the ages of 14 and 44 years, with an incidence ranging from <1 to 9.

E2F1 copy number variations contribute to spermatogenic impairment and cryptorchidism by increasing susceptibility to heat stress.

Background: Copy number variations (CNVs) play an important role in the onset of several diseases, and recently research focused on the relationship between these structural variants and diseases of the reproductive tract, including male infertility and cryptorchidism.

Objectives: To evaluate the contribution of copy number variations of E2F1 gene to idiopathic male infertility and the factors influencing expression of this gene.

Materials And Methods: We performed a retrospective study on 540 subjects recruited from September 2014 to February 2015.

Endocrine Disruption of Androgenic Activity by Perfluoroalkyl Substances: Clinical and Experimental Evidence.

Background: Considerable attention has been paid to perfluoroalkyl compounds (PFCs) because of their worldwide presence in humans, wildlife, and environment. A wide variety of toxicological effects is well supported in animals, including testicular toxicity and male infertility. For these reasons, the understanding of epidemiological associations and of the molecular mechanisms involved in the endocrine-disrupting properties of PFCs on human reproductive health is a major concern.

Aqueous extract of Eruca Sativa protects human spermatozoa from mitochondrial failure due to bisphenol A exposure.

Medicinal plants are suggested to counteract health disorders from chemical pollutants. Here we explored the possible ameliorative effect of Eruca sativa aqueous extract (ESAE) on in vitro acute functional disturbance induced by Bisphenol A (BPA), a disruptor model in human spermatozoa. Phytochemical screening, high performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) analysis and 2,2'-azino-bis [3-ethylbenzthiazoline-6-sulphonic acid]/α,α-diphenyl-β-picrylhydrazyl (ABTS/DPPH) tests disclosed antioxidant properties of ESAE, ascribed to polyphenols and flavonoids.

Impaired sperm function in infertile men relies on the membrane sterol pattern.

Membrane cholesterol removal appears a key step for the gain of fertility potential during sperm maturation. However, the membrane sterol pattern in sperm cells from infertile patients, with impaired sperm parameters, has been poorly investigated. To elucidate a causative link between sperm membrane composition in male fertility, here we have investigated the levels of cholesterol and its oxidized derivatives 7β-hydroxycholesterol and 7-keto-cholesterol in sixteen infertile patients with oligo-asthenozoospermia and 16 normozoospermic (N) fertile subjects.

Impaired Release of Vitamin D in Dysfunctional Adipose Tissue: New Cues on Vitamin D Supplementation in Obesity.

Context: Vitamin D accumulates in adipose tissue (AT), and vitamin D deficiency is frequent in obesity.

Objective: We hypothesize that trafficking of vitamin D is altered in dysfunctional AT.

Design, Patients, Settings: Fifty-four normal-weight and 67 obese males were recruited in a prospective study and randomly assigned to supplementation with 50 µg/wk 25-hydroxyvitamin-D3 or 150 µg/wk vitamin D3 for 1 year, raising dosage by 50% if vitamin D sufficiency [serum 25-hydroxyvitamin-D3 >50 nmol/L], was not achieved at 6 months; 97 subjects completed the study.

Heat Sensing Receptor TRPV1 Is a Mediator of Thermotaxis in Human Spermatozoa.

The molecular bases of sperm thermotaxis, the temperature-oriented cell motility, are currently under investigation. Thermal perception relies on a subclass of the transient receptor potential [TRP] channels, whose member TRPV1 is acknowledged as the heat sensing receptor. Here we investigated the involvement of TRPV1 in human sperm thermotaxis.