Male contribution to a couple's fecundity is important, and identifying the dietary factors that can influence male fertility potential is of high importance. Despite this importance, there are ...currently no clear clinical guidelines for male patients seeking fertility treatment. In this review, we present the most up-to-date evidence about diet and male fertility in humans. We focus on the dietary factors necessary for production of healthy functioning sperm with high fertility potential. Based on this review, men may be encouraged to use antioxidant supplements and to follow dietary patterns favoring the consumption of seafood, poultry, nuts, whole grains, fruits, and vegetables. Evidence is strongest for recommending the use of antioxidant supplements to men in couples undergoing infertility treatment—although the specific antioxidants and doses remain unclear—and increasing consumption of omega-3 fatty acids from fish and nuts.
•Metabolomic profiling is a powerful tool for mechanistic understanding of PM2.5 exposure impact.•PM2.5 exposure has metabolomic signatures related to oxidative stress, immunity, & nucleic acid ...damage.•Little is known about the specific PM2.5 species (hence sources) that drive these signatures.•Ultrafine particles were the main significant species of short-term PM2.5 exposure followed by Ni and V then Si, Al, and K.•Black carbon, Ni, V, Zn, Cu, Fe, and Se were the main significant species of long-term PM2.5 exposure.
The metabolomic signatures of short- and long-term exposure to PM2.5 have been reported and linked to inflammation and oxidative stress. However, little is known about the relative contribution of the specific PM2.5 species (hence sources) that drive these metabolomic signatures.
We aimed to determine the relative contribution of the different species of PM2.5 exposure to the perturbed metabolic pathways related to changes in the plasma metabolome.
We performed mass-spectrometry based metabolomic profiling of plasma samples among men from the Normative Aging Study to identify metabolic pathways associated with PM2.5 species. The exposure windows included short-term (one, seven-, and thirty-day moving average) and long-term (one year moving average). We used linear mixed-effect regression with subject-specific intercepts while simultaneously adjusting for PM2.5, NO2, O3, temperature, relative humidity, and covariates and correcting for multiple testing. We also used independent component analysis (ICA) to examine the relative contribution of patterns of PM2.5 species.
Between 2000 and 2016, 456 men provided 648 blood samples, in which 1158 metabolites were quantified. We chose 305 metabolites for the short-term and 288 metabolites for the long-term exposure in this analysis that were significantly associated (p-value < 0.01) with PM2.5 to include in our PM2.5 species analysis. On average, men were 75.0 years old and their body mass index was 27.7 kg/m2. Only 3% were current smokers. In the adjusted models, ultrafine particles (UFPs) were the most significant species of short-term PM2.5 exposure followed by nickel, vanadium, potassium, silicon, and aluminum. Black carbon, vanadium, zinc, nickel, iron, copper, and selenium were the significant species of long-term PM2.5 exposure. We identified several metabolic pathways perturbed with PM2.5 species including glycerophospholipid, sphingolipid, and glutathione. These pathways are involved in inflammation, oxidative stress, immunity, and nucleic acid damage and repair. Results were overlapped with the ICA.
We identified several significant perturbed plasma metabolites and metabolic pathways associated with exposure to PM2.5 species. These species are associated with traffic, fuel oil, and wood smoke. This is the largest study to report a metabolomic signature of PM2.5 species’ exposure and the first to use ICA.
Multiple meta-analyses have shown sperm count declines in Western countries spanning eight decades. Secular trends in other parameters remain unclear, as are potential predictors of these trends.
To ...analyze secular trends in semen quality and to evaluate whether factors previously found to be related to semen quality were responsible for these patterns.
This is a prospective study including 936 men of couples seeking infertility treatment who provided 1618 semen samples at a single center (2000–2017). Self-reported demographic, nutritional and reproductive characteristics were collected using standardized questionnaires. Urinary concentrations of bisphenol A, parabens and phthalates were quantified by isotope-dilution tandem mass spectrometry. Semen samples were analyzed for volume, sperm concentration, count, motility and morphology following WHO guidelines. We estimated the differences in semen parameters over time by fitting generalized linear mixed models with random intercepts to account for repeated samples while adjusting for abstinence time. We also adjusted for demographic, nutritional and environmental factors to investigate these as potential predictors of time trends.
Sperm concentration and count declined by 2.62% per year (95% CI −3.84, −1.38) and 3.12% per year (95% CI: −4.42, −1.80), corresponding to an overall decline of 37% and 42%, respectively, between 2000 and 2017. Decreasing trends were also observed for total motility (per year: −0.44 percentage units, 95% CI −0.71, −0.17) and morphologically normal sperm (per year: −0.069 percentage units, 95% CI −0.116, −0.023). These decreases reflected relative percentage declines of 15% and 16% over the 17 year study period, respectively. When reproductive factors were included in the model, the downward trends in sperm concentration and sperm count were attenuated by 29% and 26%, respectively, while the trends in motility and morphology were attenuated by 54% and 53%, respectively. Also, the downward trends in both sperm concentration and sperm morphology over time were attenuated by 19% when including the DEHP and non-DEHP metabolites, respectively.
Sperm concentration, total count, motility and morphology significantly declined between 2000 and 2017 among subfertile men. These negative trends were attenuated when considering simultaneous changes in reproductive characteristics and urinary phthalates during the course of the study.
•Sperm concentration and count declined 37% and 42%, respectively, between 2000 and 2017 among men attending a fertility center in Boston.•Total motility and morphologically normal sperm declined 15% and 16% over the 17 year study period, respectively.•When reproductive factors were included in the model, the downward trends in semen parameters were attenuated between 29% and 54%.•The downward trends in sperm concentration and morphology were attenuated by 19% when including the DEHP and non-DEHP metabolites, respectively.
Variants in the leucine-rich repeat kinase 2 gene (LRRK2) are risk factors for Parkinson's disease (PD), but their prevalence varies geographically, reflecting the locations of founder events and ...dispersion of founders' descendants.
A comprehensive literature review was conducted to identify studies providing prevalence estimates for any of ten variants in LRRK2 (G2019S, R1441C, R1441G, R1441H, I2020T, N1437H, Y1699C, S1761R, G2385R, R1628P) among individuals with PD globally. We calculated crude country-specific variant prevalence estimates and, when possible, adjusted estimates for ethno-racial composition. For clinic-based studies, probands were used over other familial cases, whereas for population-based studies, all PD cases were used.
The analysis included 161 articles from 52 countries yielding 581 prevalence estimates across the ten variants. G2019S was the most common variant, exceeding 1.0% in 26 of 51 countries with estimates. The other variants were far less common. G2385R and R1628P were observed almost exclusively in East Asian countries, where they were found in ∼5–10% of cases. All prevalence estimates adjusted for ethno-racial composition were lower than their unadjusted counterparts, although data permitting this adjustment was only available for six countries.
Except for G2019S, the LRRK2 variants covered in this review were uncommon in most countries studied. However, there were countries with higher prevalence for some variants, reflecting the uneven geographic distribution of LRRK2 variants. The fact that ethno-racial group‒adjusted estimates were lower than crude estimates suggests that estimates derived largely from clinic-based studies may overstate the true prevalence of some LRRK2 variants in PD.
•Variants in leucine-rich repeat kinase 2 (LRRK2) are linked to Parkinson's disease.•Prevalence of Parkinson's disease mutations vary by geography and race/ethnicity.•Adjustment for ethnoracial composition affects country-level prevalence estimates.•G2019S was the most common LRRK2 variant across 51 countries.
Long-term exposures to air pollution has been reported to be associated with inflammation and oxidative stress. However, the underlying metabolic mechanisms remain poorly understood.
We aimed to ...determine the changes in the blood metabolome and thus the metabolic pathways associated with long-term exposure to outdoor air pollution and ambient temperature.
We quantified metabolites using mass-spectrometry based global untargeted metabolomic profiling of plasma samples among men from the Normative Aging Study (NAS). We estimated the association between long-term exposure to PM
, NO
, O
, and temperature (annual average of central site monitors) with metabolites and their associated metabolic pathways. We used multivariable linear mixed-effect regression models (LMEM) while simultaneously adjusting for the four exposures and potential confounding and correcting for multiple testing. As a reduction method for the intercorrelated metabolites (outcome), we further used an independent component analysis (ICA) and conducted LMEM with the same exposures.
Men (N = 456) provided 648 blood samples between 2000 and 2016 in which 1158 metabolites were quantified. On average, men were 75.0 years and had an average body mass index of 27.7 kg/m
. Almost all men (97%) were not current smokers. The adjusted analysis showed statistically significant associations with several metabolites (58 metabolites with PM
, 15 metabolites with NO
, and 6 metabolites with temperature) while no metabolites were associated with O
. One out of five ICA factors (factor 2) was significantly associated with PM
. We identified eight perturbed metabolic pathways with long-term exposure to PM
and temperature: glycerophospholipid, sphingolipid, glutathione, beta-alanine, propanoate, and purine metabolism, biosynthesis of unsaturated fatty acids, and taurine and hypotaurine metabolism. These pathways are related to inflammation, oxidative stress, immunity, and nucleic acid damage and repair.
Using a global untargeted metabolomic approach, we identified several significant metabolites and metabolic pathways associated with long-term exposure to PM
, NO
and temperature. This study is the largest metabolomics study of long-term air pollution, to date, the first study to report a metabolomic signature of long-term temperature exposure, and the first to use ICA in the analysis of both.
Abstract
STUDY QUESTION
Is marijuana smoking associated with semen quality, sperm DNA integrity or serum concentrations of reproductive hormones among subfertile men?
SUMMARY ANSWER
Men who had ever ...smoked marijuana had higher sperm concentration and count and lower serum FSH concentrations than men who had never smoked marijuana; no differences were observed between current and past marijuana smokers.
WHAT IS KNOWN ALREADY
Studies of marijuana abuse in humans and animal models of exposure to marijuana suggest that marijuana smoking adversely impacts spermatogenesis. Data is less clear for moderate consumption levels and multiple studies have found higher serum testosterone concentrations among marijuana consumers.
STUDY DESIGN, SIZE, DURATION
This longitudinal study included 662 subfertile men enroled at the Massachusetts General Hospital Fertility Center between 2000 and 2017. The men provided a total of 1143 semen samples; 317 men also provided blood samples in which we measured reproductive hormones.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Use of marijuana and other drugs was self-reported at baseline. Standard protocols were followed for measuring semen quality, sex hormones and DNA integrity. We used linear mixed effect models with a random intercept to evaluate the associations of self-reported marijuana smoking at enrolment with semen parameters from subsequently collected samples, and linear regression models for sperm DNA integrity and serum reproductive hormones, while adjusting for confounders including smoking and cocaine use.
MAIN RESULTS AND THE ROLE OF CHANCE
Men who had ever smoked marijuana (N = 365) had significantly higher sperm concentration (62.7 (95% confidence interval: 56.0, 70.3) million/mL) than men who had never smoked marijuana (N = 297) (45.4 (38.6, 53.3) million/mL) after adjusting for potential confounders (P = 0.0003). There were no significant differences in sperm concentration between current (N = 74) (59.5 (47.3, 74.8) million/mL) and past marijuana smokers (N = 291) (63.5 (56.1, 72.0) million/mL; P = 0.60). A similar pattern was observed for total sperm count. Furthermore, the adjusted prevalence of sperm concentration and total sperm motility below WHO reference values among marijuana smokers was less than half that of never marijuana smokers. Marijuana smokers had significantly lower follicle stimulating hormone (FSH) concentrations than never marijuana smokers (−16% (−27%, −4%)) and there were no significant differences between current and past marijuana smokers (P = 0.53). Marijuana smoking was not associated with other semen parameters, with markers of sperm DNA integrity or with reproductive hormones other than FSH. Chance findings cannot be excluded due to the multiple comparisons.
LIMITATIONS, REASONS FOR CAUTION
Our results may not be generalisable to men from the general population. Marijuana smoking was self-reported and there may be misclassification of the exposure.
WIDER IMPLICATIONS OF THE FINDINGS
These findings are not consistent with a deleterious effect of marijuana on testicular function. Whether these findings are reflective of the previously described role of the endocannabinoid system in spermatogenesis or a spurious association requires confirmation in further studies.
STUDY FUNDING/COMPETING INTEREST(S)
The project was funded by grants R01ES009718 and P30ES000002 from the National Institute of Environmental Health Sciences (NIEHS). None of the authors has any conflicts of interest to declare.
TRIAL REGISTRATION NUMBER
N/A.
Endocrine disruptors, such as phthalates, are suspected of affecting reproductive function. The Mesalamine and Reproductive Health Study (MARS) was designed to address the physiological effect of in ...vivo phthalate exposure on male reproduction in patients with Inflammatory Bowel Disease (IBD). As part of this effort, the effect on sperm RNAs to DBP exposure were longitudinally assessed using a cross-over cross-back binary design of high or background, exposures to DBP. As the DBP level was altered, numerous sperm RNA elements (REs) were differentially expressed, suggesting that exposure to or removal from high DBP produces effects that require longer than one spermatogenic cycle to resolve. In comparison, small RNAs were minimally affected by DBP exposure. While initial study medication (high or background) implicates different biological pathways, initiation on the high-DBP condition activated oxidative stress and DNA damage pathways. The negative correlation of REs with specific genomic repeats suggests a regulatory role. Using ejaculated sperm, this work provides insight into the male germline's response to phthalate exposure.
There is growing acceptance that nutrition may be related to fertility and specifically to assisted reproductive technologies success in women; however, there is still no specific dietary guidance.
...The objective of the study was to evaluate the relationship between pretreatment adherence to various dietary patterns and outcomes of assisted reproductive technologies.
We followed up 357 women enrolled in the prospective Environment and Reproductive Health (EARTH) study, who underwent 608 assisted reproductive technologies cycles (2007–2017). Using a validated food frequency questionnaire completed prior to treatment, we assessed adherence to the Mediterranean diet, the alternate Healthy Eating Index 2010, the Fertility Diet (developed based on risk factors for anovulatory infertility), and a profertility diet we developed based on factors previously related to assisted reproductive technologies outcomes (higher intake of supplemental folic acid, vitamin B12, vitamin D, low- rather than high-pesticide residue produce, whole grains, dairy, soy foods, and seafood rather than other meats).
Higher adherence to the alternate Healthy Eating Index 2010 and Fertility Diet was not related to live birth following assisted reproductive technologies. Women in the second through the fourth quartiles of Mediterranean diet adherence had significantly higher probability of live birth (0.44, 95% confidence interval, 0.39–0.49) compared with women in the first quartile (0.31, 95% confidence interval, 0.25–0.39); however, there was no additional benefit of adherence to the Mediterranean diet above the second quartile. Increased adherence to the profertility diet was linearly associated with assisted reproductive technologies outcomes. The adjusted odds (95% confidence interval) of implantation, clinical pregnancy, and live birth were higher by 47% (21%, 77%), 43% (19%, 72%), and 53% (26%, 85%), respectively, per SD increase. The adjusted difference in the proportion of cycles resulting in live birth for women in the fourth vs first quartile of adherence to the profertility diet was 0.28 (95% confidence interval, 0.16–0.38). While the profertility diet was not related to estradiol levels, oocyte counts, or endometrial thickness, it was inversely associated with clinical pregnancy loss (odds ratio, 0.69, 95% confidence interval, 0.53–0.90 per SD increase).
Higher pretreatment adherence to the profertility diet was associated with an increased probability of live birth among women undergoing assisted reproductive technologies. Commonly recommended dietary advice such as adhering to the Mediterranean diet may not provide the most appropriate guidance for women undergoing infertility treatment in the United States.
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•Quinolinic acid (QA) is a neuroactive metabolite.•QA is implicated in the pathogenesis of several neurological disorders.•Urinary concentrations of several phthalate metabolites were ...positively associated with QA.•This novel finding may partially account for the associations of phthalate exposures with neurodevelopmental disorders.
Quinolinic acid (QA), a neuroactive metabolite produced during tryptophan degradation, is implicated in the pathogenesis of several neurological disorders. Phthalates are structurally similar to QA, and exposure to phthalates has demonstrated increased QA production and excretion in rodent studies. We recently showed that very high exposure to dibutyl phthalate was associated with higher concentrations of urinary QA in men. However, no human studies examined the associations between background (low) phthalate exposures and QA.
To examine the associations of urinary concentrations of phthalate metabolites with QA.
Female participants (N = 126) who participated in a prospective cohort study at the Massachusetts General Hospital Fertility Center provided 758 urine samples (273 during pregnancy and 485 during non-pregnancy). Concentrations of 11 phthalate metabolites and QA in urine were measured. We used multivariable linear mixed effect models to estimate the percent change in urinary QA concentrations associated with a doubling (100%) of urinary phthalate metabolite concentration, and evaluated whether there was effect modification by pregnancy status.
Women’s mean (standard deviation) age was 34.2 (4.0) years with a body mass index of 23.5 (3.7) kg/m2. The women were primarily Caucasian (92%), had at least a college degree (98%), and none were current smokers. Pairwise Spearman correlations between concentrations for phthalate metabolites and QA measured in the same urine samples ranged from 0.36 for MEHP to 0.68 for dibutyl phthalate (DBP) metabolites. In multivariable-adjusted models, the percent change in urinary QA concentrations was significantly higher for each doubling of several urinary phthalate metabolite concentrations. For example, each doubling of DBP metabolites was associated with a 13.7% (95%CI: 10.6, 16.9)% higher QA. Associations between the low molecular weight phthalate metabolites and QA were stronger among samples collected during pregnancy as compared to non-pregnancy samples from the same women.
Urinary concentrations of several phthalate metabolites were positively associated with QA among women. These findings, along with the known neurotoxicity of QA, warrant the need to examine whether QA concentrations may serve as a pathway for the adverse neurodevelopment outcomes found in children’s health studies.
Exposure to some environmental chemicals is ubiquitous and linked to a variety of adverse outcomes, including children's health. While few studies have assessed the contribution of both male and ...female exposures to children's health, understanding the patterns of couple's exposure is needed to understand their joint effects.
We assessed the correlation patterns between male and female partners' concentrations of 37 environmental chemical biomarkers. We also assessed the temporal reliability of the biomarkers within couples.
We calculated Spearman pairwise correlations between specific gravity adjusted urinary biomarker concentrations and hair mercury concentrations among 380 couples enrolled in the Environment and Reproductive Health (EARTH) study at the Massachusetts General Hospital Fertility Center (2004–2017). We calculated intra-class correlation coefficients (ICCs) for couple's biomarkers to assess the temporal variability of these exposures within a couple using multiple paired-samples from couples.
All biomarkers were positively correlated within couples (range: 0.05 for tert-butylphenyl phenyl phosphate to 0.66 for triclosan). In general, the biomarkers with the highest within couple correlation were those of chemicals for which diet (e.g., di(2-ethylhexyl) phthalate), personal care products use (e.g., triclosan, benzophenone-3), and the indoor environment (e.g., 2,5-dichlorophenol) are considered primary exposure sources. Most other biomarkers were moderately correlated (0.3–<0.6). Similar patterns of temporal reliability were observed across biomarkers.
Urinary concentrations of several biomarkers were mostly moderately correlated within couples, suggesting similar exposure sources. Future epidemiological studies should collect samples from both partners to be able to accurately determine the contribution of maternal and paternal exposures to offspring health.
•Understanding the patterns of couple’s exposure is needed to understand their joint effects.•All 37 environmental biomarkers were positively correlated within couples.•Correlations were moderately high for chemicals with diet, personal products, and indoor environment are primary sources.•Similar patterns were observed across biomarkers for measures of temporal reliability.
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