Relationships between heavy metal concentrations in three different body fluids and male reproductive parameters: a pilot study

<p>Abstract</p> <p>Background</p> <p>Animal studies have shown the reproductive toxicity of a number of heavy metals. Very few human observational studies have analyzed the relationship between male reproductive function and heavy metal concentrations in diverse biological fluids.</p> <p>Methods</p> <p>The current study assessed the associations between seminal and hormonal parameters and the concentration of the 3 most frequent heavy metal toxicants (lead, cadmium and mercury) in three different body fluids. Sixty one men attending infertility clinics that participated in a case-control study to explore the role of environmental toxins and lifestyles on male infertility were analyzed. Concentration of lead, cadmium and mercury were measured in blood and seminal plasma and whole blood using anodic stripping voltammetry and atomic absorption spectrophotometry. Serum samples were analyzed for follicle-stimulating hormone, luteinizing hormone and testosterone. Semen analyses were performed according to World Health Organization criteria. Mann-Whitney test and Spearman's rank correlations were used for unadjusted analyses. Multiple linear regression models were performed controlling for age, body mass index and number of cigarettes per day.</p> <p>Results</p> <p>There were no significant differences between cases and controls in the concentrations of heavy metals in any of the three body fluids. In multivariate analyses using all subjects no significant associations were found between serum hormone levels and metal concentrations. However there was a significant positive association between the percentage of immotile sperms and seminal plasma levels of lead and cadmium.</p> <p>Conclusions</p> <p>Our results suggest that the presence of lead and cadmium in the reproductive tract of men may be related to a moderate alteration of their seminal parameters.</p

Recent cadmium exposure among male partners may affect oocyte fertilization during in vitro fertilization (IVF)

We recently reported evidence suggesting associations between urine cadmium concentrations, reflecting long-term exposure, measured in 25 female patients (relative risk = 1.41, P = 0.412) and 15 of their male partners (relative risk = 0.19, P = 0.097) and oocyte fertilization in vitro. Blood cadmium concentrations reflect more recent exposure. We here incorporate those measures into our prior data set and employ multivariable log-binomial regression models to generate hypotheses concerning the relative effects of long-term and recent cadmium exposure on oocyte fertilization in vitro. No association is indicated for blood cadmium from women and oocyte fertilization, adjusted for urine cadmium and creatinine, blood lead and mercury, age, race/ethnicity and cigarette smoking (relative risk = 0.88, P = 0.828). However, we suggest an inverse adjusted association between blood cadmium from men and oocyte fertilization (relative risk = 0.66, P = 0.143). These results suggest that consideration of long-term and recent exposures are both important for assessing the effect of partner cadmium levels on oocyte fertilization in vitro

First Transcriptome of the Testis-Vas Deferens-Male Accessory Gland and Proteome of the Spermatophore from Dermacentor variabilis (Acari: Ixodidae)

Ticks are important vectors of numerous human diseases and animal diseases. Feeding stimulates spermatogenesis, mating and insemination of male factors that trigger female reproduction. The physiology of male reproduction and its regulation of female development are essentially a black box. Several transcriptomes have catalogued expression of tick genes in the salivary glands, synganglion and midgut but no comprehensive investigation has addressed male reproduction and mating. Consequently, a new global approach using transcriptomics, proteomics, and quantitative gene expression is needed to understand male reproduction and stimulation of female reproduction

Combinations of physiologic estrogens with xenoestrogens alter calcium and kinase responses, prolactin release, and membrane estrogen receptor trafficking in rat pituitary cells

<p>Abstract</p> <p>Background</p> <p>Xenoestrogens such as alkylphenols and the structurally related plastic byproduct bisphenol A have recently been shown to act potently via nongenomic signaling pathways and the membrane version of estrogen receptor-α. Though the responses to these compounds are typically measured individually, they usually contaminate organisms that already have endogenous estrogens present. Therefore, we used quantitative medium-throughput screening assays to measure the effects of physiologic estrogens in combination with these xenoestrogens.</p> <p>Methods</p> <p>We studied the effects of low concentrations of endogenous estrogens (estradiol, estriol, and estrone) at 10 pM (representing pre-development levels), and 1 nM (representing higher cycle-dependent and pregnancy levels) in combinations with the same levels of xenoestrogens in GH₃/B6/F10 pituitary cells. These levels of xenoestrogens represent extremely low contamination levels. We monitored calcium entry into cells using Fura-2 fluorescence imaging of single cells. Prolactin release was measured by radio-immunoassay. Extracellular-regulated kinase (1 and 2) phospho-activations and the levels of three estrogen receptors in the cell membrane (ERα, ERβ, and GPER) were measured using a quantitative plate immunoassay of fixed cells either permeabilized or nonpermeabilized (respectively).</p> <p>Results</p> <p>All xenoestrogens caused responses at these concentrations, and had disruptive effects on the actions of physiologic estrogens. Xenoestrogens reduced the % of cells that responded to estradiol via calcium channel opening. They also inhibited the activation (phosphorylation) of extracellular-regulated kinases at some concentrations. They either inhibited or enhanced rapid prolactin release, depending upon concentration. These latter two dose-responses were nonmonotonic, a characteristic of nongenomic estrogenic responses.</p> <p>Conclusions</p> <p>Responses mediated by endogenous estrogens representing different life stages are vulnerable to very low concentrations of these structurally related xenoestrogens. Because of their non-classical dose-responses, they must be studied in detail to pinpoint effective concentrations and the directions of response changes.</p

Utjecaj toksičnosti metala na reprodukcijsku funkciju u muškaraca

A combination of genetic, environmental and lifestyle factors contributes to adverse effects on the reproductive health in men. Metals are pervasive in food, water, air, tobacco smoke, and alcoholic beverages. Experimental studies suggest that many metals have adverse effects on the male reproductive function. However, information about reproductive effects of human exposure to metals is scarce and/or inconsistent. This review summarises the information from epidemiological studies of the effects of metal exposure on reproductive function in men. Factors capable of affecting these relationships were identifi ed and discussed. A particular attention is given to the studies considering influence of concomitant exposure to various metals. These studies have generally confirmed that even moderate- to low-level exposure to lead affects certain reproductive parameters, and that exposure to cadmium affects the prostate function and serum testosterone levels. Adverse effects of mercury, manganese, chromium and arsenic on semen quality and altered serum hormone are less well documented. There is no clear evidence that boron exposure may impair reproductive health in men. Only a few studies have investigated reproductive effects of concomitant exposure to several metals and controlled for potential confounders. Future studies should consider the contribution of combined exposure to various metals and/or other factors that may influence individual susceptibility to reproductive health impairment in men.Postoje indikacije da kombinacija genetskih, okolišnih i čimbenika načina života pridonosi uočenom poremećaju reprodukcijskog zdravlja u muškaraca. Metali su široko rasprostranjeni u čovjekovu okolišu te u hrani, vodi, zraku, cigaretnom dimu i alkoholnim pićima. Rezultati eksperimentalnih istraživanja sugeriraju štetne učinke većine ispitivanih metala na mušku reprodukcijsku funkciju. Međutim, odgovarajuća su istraživanja u ljudi oskudna. Ovaj rad sažima rezultate dosadašnjih epidemioloških istraživanja o učincima izloženosti metalima na mušku reprodukcijsku funkciju. Poseban naglasak dan je istraživanjima koja su razmatrala utjecaj istodobne izloženosti različitim metalima uz čimbenike čovjekova načina života i njihovo međudjelovanje na reprodukcijske učinke. Objavljeni rezultati daju dovoljno dokaza o štetnom djelovanju olova i žive na neke reprodukcijske parametre te kadmija na poremećaj prostate i razinu testosterona u serumu, čak u uvjetima umjerene do niske razine izloženosti. Manje je dokaza o štetnom djelovanju na kvalitetu sjemena i razinu spolnih hormona nađeno za mangan. Podaci koji upućuju na moguće štetno djelovanje arsena ili kroma nisu dosljedni, dok o štetnom djelovanju bora na mušku reprodukcijsku funkciju nema jasnih podataka. Utjecaj potencijalno uzročnih varijabli uzet je u obzir samo u nekoliko radova. Stoga buduća istraživanja poremećaja reprodukcijskog zdravlja u muškaraca trebaju razmatrati doprinos istovremene izloženosti različitim metalima koji u kombinaciji s ostalim čimbenicima mogu utjecati na osobnu (pre)osjetljivost

SLXL1, a novel acrosomal protein, interacts with DKKL1 and is involved in fertilization in mice

BACKGROUND: Spermatogenesis is a complex cellular developmental process which involves diverse families of genes. The Xlr (X-linked, lymphocyte regulated) family includes multiple members, only a few of which have reported functions in meiosis, post-meiotic maturation, and fertilization of germ cells. Slx-like1 (Slxl1) is a member of the Xlr family, whose expression and function in spermatogenesis need to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: The mRNA and protein expression and localization of Slxl1 were investigated by RT-PCR, Western blotting and immunohistochemistry in different tissues and at different stages of spermatogenesis. The interacting partner of SLXL1 was examined by co-immunoprecipitation and co-localization. Assessment of the role of SLXL1 in capacitation, acrosome reaction, zona pellucida binding/penetration, and fertilization was carried out in vitro using blocking antisera. The results showed that Slxl1 mRNA and protein were specifically expressed in the testis. SLXL1 was exclusively located in the acrosome of post-meiotic germ cells and interacts with DKKL1 (Dickkopf-like1), which is an acrosome-associated protein and plays an important role in fertilization. The rates of zona pellucida binding/penetration and fertilization were significantly reduced by the anti-SLXL1 polyclonal antiserum. CONCLUSIONS/SIGNIFICANCE: SLXL1 is the first identified member of the XLR family that is associated with acrosome and is involved in zona pellucid binding/penetration and subsequent fertilization. These results, together with previous studies, suggest that Xlr family members participate in diverse processes from meiosis to fertilization during spermatogenesis

Reactive oxygen species and male reproductive hormones

Reports of the increasing incidence of male infertility paired with decreasing semen quality have triggered studies on the effects of lifestyle and environmental factors on the male reproductive potential. There are numerous exogenous and endogenous factors that are able to induce excessive production of reactive oxygen species (ROS) beyond that of cellular antioxidant capacity, thus causing oxidative stress. In turn, oxidative stress negatively affects male reproductive functions and may induce infertility either directly or indirectly by affecting the hypothalamus-pituitary-gonadal (HPG) axis and/or disrupting its crosstalk with other hormonal axes. This review discusses the important exogenous and endogenous factors leading to the generation of ROS in different parts of the male reproductive tract. It also highlights the negative impact of oxidative stress on the regulation and cross-talk between the reproductive hormones. It further describes the mechanism of ROS-induced derangement of male reproductive hormonal profiles that could ultimately lead to male infertility. An understanding of the disruptive effects of ROS on male reproductive hormones would encourage further investigations directed towards the prevention of ROS-mediated hormonal imbalances, which in turn could help in the management of male infertility