Zinc-associated phospholipid metabolic alterations and their impacts on ALT levels in workers.

Zinc (Zn) is an essential trace element that is required for various biological functions, but excessive exposure to Zn is associated with many disorders and even diseases. However, the health effects and underlying mechanisms of long-term and high concentration exposure of Zn remain to be unclear. In the present study, we investigated the association between occupational exposure to Zn and liver function indicators (like alanine aminotransferase (ALT)) in workers. We found a positive association between Zn exposure and ALT level in workers. Workers having higher blood Zn (7735.65 (1159.15) µg/L) shows a 30.4 % increase in ALT level compared to those with lower blood Zn (5969.30 (989.26) µg/L). Furthermore, we explored the effects of phospholipids (PLs) and their metabolism on ALT level and discovered that Zn exposure in workers was associated with changes in PL levels and metabolism, which had further effects on increased ALT levels in workers. The study provides insights into the relationship between occupational Zn exposure and liver function, highlights the risk of long-term exposure to high concentrations of Zn, and paves the way for understanding the underlying mechanisms of Zn exposure on human health.

Using Machine Learning to Construct the Blood-Follicle Distribution Models of Various Trace Elements and Explore the Transport-Related Pathways with Multiomics Data.

Permeabilities of various trace elements (TEs) through the blood-follicle barrier (BFB) play an important role in oocyte development. However, it has not been comprehensively described as well as its involved biological pathways. Our study aimed to construct a blood-follicle distribution model of the concerned TEs and explore their related biological pathways. We finally included a total of 168 women from a cohort of in vitro fertilization-embryo transfer conducted in two reproductive centers in Beijing City and Shandong Province, China. The concentrations of 35 TEs in both serum and follicular fluid (FF) samples from the 168 women were measured, as well as the multiomics features of the metabolome, lipidome, and proteome in both plasma and FF samples. Multiomics features associated with the transfer efficiencies of TEs through the BFB were selected by using an elastic net model and further utilized for pathway analysis. Various machine learning (ML) models were built to predict the concentrations of TEs in FF. Overall, there are 21 TEs that exhibited three types of consistent BFB distribution characteristics between Beijing and Shandong centers. Among them, the concentrations of arsenic, manganese, nickel, tin, and bismuth in FF were higher than those in the serum with transfer efficiencies of 1.19-4.38, while a reverse trend was observed for the 15 TEs with transfer efficiencies of 0.076-0.905, e.g., mercury, germanium, selenium, antimony, and titanium. Lastly, cadmium was evenly distributed in the two compartments with transfer efficiencies of 0.998-1.056. Multiomics analysis showed that the enrichment of TEs was associated with the synthesis and action of steroid hormones and the glucose metabolism. Random forest model can provide the most accurate predictions of the concentrations of TEs in FF among the concerned ML models. In conclusion, the selective permeability through the BFB for various TEs may be significantly regulated by the steroid hormones and the glucose metabolism. Also, the concentrations of some TEs in FF can be well predicted by their serum levels with a random forest model.

Exogenous Metals Atlas in Spermatozoa at Single-Cell Resolution in Relation to Human Semen Quality.

While exogenous metal/metalloid (metal) exposure has been associated with reduced human semen quality, no study has assessed the associations of exogenous metals in human spermatozoa with semen quality. Here, we developed a strategy to explore the associations between exogenous metals in spermatozoa at single-cell resolution and human semen quality among 84 men screened as sperm donors, who provided 266 semen samples within 90 days. A cellular atlas of exogenous metals at the single-cell level was created with mass cytometry (CyTOF) technology, which concurrently displayed 18 metals in more than 50 000 single sperm. Exogenous metals in spermatozoa at single-cell resolution were extremely heterogeneous and diverse. Further analysis using multivariable linear regression and linear mixed-effects models revealed that the heterogeneity and prevalence of the exogenous metals at single-cell resolution were associated with semen quality. The heterogeneity of lead (Pb), tin (Sn), yttrium (Y), and zirconium (Zr) was negatively associated with sperm concentration and count, while their prevalence showed positive associations. These findings revealed that the heterogeneous properties of exogenous metals in spermatozoa were associated with human semen quality, highlighting the importance of assessing exogenous metals in spermatozoa at single-cell resolution to evaluate male reproductive health risk precisely.

MARS1 mutations linked to familial trigeminal neuralgia via the integrated stress response.

BACKGROUND: While new genetic analysis methods are widely used in the clinic, few researchers have focused on trigeminal neuralgia (TN) with familial clustering (≥ 2 TN patients in one kindred family). Previous literature suggests that familial trigeminal neuralgia (FTN) may be associated with inherited genetic factors. To date, few next-generation sequencing studies have been reported for FTN. This study investigated the pathogenic mechanism of FTN by using whole-exome sequencing (WES) technology, which may enhance our understanding of human TN pathophysiology.  METHOD: We performed WES for 7 probands from families of FTN. Sanger sequencing was performed for two control groups (FTN family members group and nonfamilial TN subject group) to potentially identify new FTN-related gene mutations. In families where FTN probands carried potentially pathogenic gene mutations, the ribonucleic acid (RNA) of FTN probands and related family members, as well as nonfamilial TN patients were analysed by RNA sequencing (RNA-seq) to confirm differential gene expression. RESULTS: Seven probands were derived from 3 Chinese families. WES and Sanger sequencing identified MARS1 mutation c.2398C > A p.(Pro800Thr) in Family 1. MARS1 mutation was confirmed in 14/26 [53.8%] members of Family 1 in FTN family member group, while none of nonfamilial TN subjects had this MARS1 mutation. RNA-seq showed that 3 probands in Family 1 had higher expression of Fosl1 (Fos-like antigen 1) and NFE2 (Nuclear factor, erythroid 2) than 3 subjects in the nonfamilial TN subject group. Fosl1 and NFE2 are genes related to integrated stress response (ISR). CONCLUSION: MARS1 mutations may cause chronic activation of ISR, contribute to ISR pathophysiological changes in FTN, and cause/accelerate peripheral nerve degeneration. The findings of this study can enrich our knowledge of the role of molecular genetics in TN in humans.

Per- and polyfluoroalkyl substances (PFAS) exposure in women seeking in vitro fertilization-embryo transfer treatment (IVF-ET) in China: Blood-follicular transfer and associations with IVF-ET outcomes.

As follicular fluid constitutes a critical microenvironment for the development of oocytes, investigation of environmental contaminants in follicular fluid may facilitate a better understanding of the influence of environmental exposure on reproductive health. In the present study, we aimed to investigate per- and polyfluoroalkyl substances (PFAS) exposure in women receiving in vitro fertilization-embryo transfer (IVF-ET) treatment, determine the blood-follicle transfer efficiencies (BFTE) of PFAS, and explore potential associations between PFAS exposure and selected IVF-ET outcomes. Our results revealed that n-PFOA was the most abundant PFAS in both serum and follicular fluid (FF) (median = 5.85 and 5.56 ng/mL, respectively), followed by n-PFOS (4.95 and 4.28 ng/mL), 6:2 Cl-PFESA (2.18 and 2.10 ng/mL), PFNA (1.37 and 1.37 ng/mL), PFUdA (0.33 and 0.97 ng/mL), PFDA (0.37 and 0.66 ng/mL), PFHxS (0.42 and 0.39 ng/mL), and PFHpS (0.11 and 0.10 ng/mL). The median BFTE ranged from 0.65 to 0.92 for individual PFAS, indicating a relatively high tendency of PFAS to cross the blood-follicle barrier (BFB). An inverted V-shaped trend was observed between the median BFTE and the number of fluorinated carbon atoms or the log Kow (octanol-water partition coefficient) for individual PFAS, suggesting the influence by physicochemical properties and molecular structures. Although our data did not find any clear pattern in the link between blood or follicular fluid concentrations of PFAS and selected IVF-ET outcomes, our study raises the need for better characterization of exposure to environmental chemicals in follicular fluid together with its potential influence on reproductive health.

Enrichment of boron element in follicular fluid and its potential effect on the immune function.

The blood-follicle barrier (BFB) between the blood and follicular fluid (FF) can maintain the microenvironment balance of oocyte. Boron, an exogenous environmental trace element, has been found to possibly play an important role in oocyte maturation. This study aimed to examine the distribution characteristics of boron across the BFB and find the potential effect of boron on FF microenvironment. We analyzed the concentration of boron in paired FF and serum collected from 168 women undergoing in vitro fertilization and embryo transfer in Beijing City and Shandong Province, China. To explore the potential health impact of boron enrichment in oocyte maturation, a global proteomics analysis was conducted to tentatively correlate the protein levels with the boron enrichment. Interestingly, the results showed that the concentration of boron in FF (34.5 ng/mL) was significantly higher than that in serum (22.0 ng/mL), with a median concentration ratio of 1.52. Likewise, the concentrations of boron in FF and serum were positively correlated (r = 0.446), suggesting that boron concentration in serum can represent its concentration in follicular fluid to a large extent.. This is the first time to observe the enrichment of boron in the FF to our knowledge. It is interesting to observe a total of 13 proteins, which mainly belong to immunoglobulin class, were positively correlated with boron concentration in FF. We concluded that boron, as one environmental trace element, was enriched in FF from blood validated by two area in north china, which may be involved in an increased level of immune processes of immunoglobulins.

Early pregnancy loss: Do Per- and polyfluoroalkyl substances matter?

Per- and poly-fluorinated substances (PFASs) with endocrine disrupting effect can efficiently transfer across the blood-follicle barrier. However, it is still controversial and attracting extensive public concern that whether PFASs can affect the human fertility potential. Therefore, we aimed to analyze the associations of women's exposure to PFASs with pregnancy loss, the relevant processes of fertilization, zygote implantation, and embryo development by using a prospective cohort study. The women undergoing in vitro fertilization-embryo transfer (IVF-ET) treatment were recruited in Beijing City (Beijing Center) and Yantai City (Yantai Center) in China during 2015-2017. A total of 305 women were recruited before the IVF-ET treatment. Twelve PFASs were measured in their serum samples collected in the day before the IVF-ET treatment, as well as in the human chorionic gonadotropin (hCG) day. The three IVF-ET outcomes were included, i.e. hCG test negative, clinical pregnancy failure (CPF), and preclinical spontaneous abortion. Nine serum PFASs had detection rate of >70% in Beijing and Yantai centers. The exposure patterns to PFASs between these two centers were overall different. For Beijing Center, we only found a positive association of perflurodecanoic acid (PFDA) with the risk of CPF [RR = 2.28 (95 %CI: 1.02-5.11)], but there is a reverse trend in Yantai Center with [RR = 0.45 (95 %CI: 0.23-0.85)]. However, the serum concentration of PFDA in Beijing Center was relatively lower than that of Yantai Center. Other significant associations of the detected PFASs with the IVF-ET outcomes, or with the relevant clinical processes, were not found. The multi-pollutant regression model of the Bayesian kernel machine regression suggested that there were no joint effects between various PFASs on the concerned outcomes. Overall, we suggest that most PFAS were not associated with early pregnancy loss at the current exposure levels. As for the PFDA, there may exist susceptibility of different populations.

Serum zinc concentration and risk of adverse outcomes to in vitro fertilization and embryo transfer: A prospective cohort study in northern China.

Zinc (Zn) plays an important role in female reproductive health. Few studies have currently assessed the effects of female Zn level on the outcome of in vitro fertilization-embryo transfer (IVF-ET). This study investigated the association between serum Zn concentration and IVF-ET outcomes, and the potential effects of some lifestyles on this association. A prospective cohort study design was adopted, and 305 women undergoing IVF-ET were recruited from two cities, Beijing and Shandong, in northern China. Fasting blood specimens were obtained on the day prior to the first treatment cycle. A questionnaire was used to collect demographic characteristics and lifestyle information. Serum Zn concentration was measured using inductively coupled plasma-mass spectrometry. Female serum Zn levels in Beijing center were found to be significantly higher than those in Shandong center. Women who failed to achieve clinical pregnancy had significantly lower Zn concentrations among Shandong subjects, but not in Beijing or the total participants in both centers. For Beijing participants, no statistically significant associations were found between Zn concentrations and the failure risk of IVF-ET [adjusted relative risk (aRR) = 0.65, 95% confidence interval (CI): 0.37-1.15]. For Shandong participants, lower Zn concentrations (< 610.3 ng/mL) were associated with a 66% increased risk of IVF-ET failure (aRR = 1.66, 95% CI: 1.10-2.51). Also, significantly positive correlations were observed between Zn concentrations and the habitual consumption of two food types, including fresh vegetables and beans or bean products, but this was not the case in Beijing. It was concluded that the effect of serum Zn concentrations on IVF-ET outcome may vary by the geographic location. Lower Zn levels might be a risk factor for IVF-ET failure among Shandong women, which can be addressed by adjusting the food intakes. These findings have implications for human infertility treatment and public health problem addressing.

Association between exposure of light rare earth elements and outcomes of in vitro fertilization-embryo transfer in North China.

The adverse health effects of rare earth elements (REEs) on reproductive health remain a subject of debate, and few clinical observations are available. This study investigated the association between light REEs (LREEs) exposure and the outcome of in vitro fertilization-embryo transfer (IVF-ET). We recruited a total of 305 women undergoing IVF-ET in Beijing City and Shandong Province of northern China. Their demographic information and lifestyle characteristics were collected using questionnaires at enrollment. Fasting blood samples were collected on the day before the IVF-ET treatment cycle began. Serum concentrations of the LREEs of concern were analyzed using inductively coupled plasma-mass spectrometry, and four LREEs were measured with a high detection rate, including lanthanum (La), cerium (Ce), praseodymium (Pr), and neodymium (Nd). We found that a higher serum La concentration was associated with a 30% increased likelihood of clinical pregnancy failure [relative risk (RR) = 1.30, 95% confidence interval (CI): 1.00-1.67] and a 230% increased likelihood of preclinical spontaneous abortion (RR = 3.30, 95% CI: 1.57-6.94). There was a negative correlation between serum La concentration and the number of good-quality oocytes. For the other LREEs, no statistically significant associations were observed. We concluded that a high serum La concentration may have an adverse effect on IVF-ET outcomes.