Multi-omics reveal disturbance of glucose homeostasis in pregnant rats exposed to short-chain perfluorobutanesulfonic acid.

Perfluorobutanesulfonic acid (PFBS), a short-chain alternative to perfluorooctanesulfonic acid (PFOS), is widely used in various products and is increasingly present in environmental media and human bodies. Recent epidemiological findings have raised concerns about its potential adverse health effects, although the specific toxic mechanism remains unclear. This study aimed to investigate the metabolic toxicity of gestational PFBS exposure in maternal rats. Pregnant Sprague Dawley (SD) rats were randomly assigned to three groups and administered either 3% starch gel (control), 5, or 50 mg/kg bw·d PFBS. Oral glucose tolerance tests (OGTT) and lipid profiles were measured, and integrated omics analysis (transcriptomics and non-targeted metabolomics) was employed to identify changes in genes and metabolites and their relationships with metabolic phenotypes. The results revealed that rats exposed to 50 mg/kg bw·d PFBS exhibited a significant decrease in 1-h glucose levels and the area under the curve (AUC) of OGTT compared with the starch group. Transcriptomics analysis indicated significant alterations in gene expression related to cytochrome P450 exogenous metabolism, glutathione metabolism, bile acid secretion, tumor pathways, and retinol metabolism. Differentially expressed metabolites (DEMs) were enriched in pathways such as pyruvate metabolism, the glucagon signaling pathway, central carbon metabolism in cancer, and the citric acid cycle. Co-enrichment analysis and pairwise correlation analysis among genes, metabolites, and outcomes identified several differentially expressed genes (DEGs), including Gstm1, Kit, Adcy1, Gck, Ppp1r3c, Ppp1r3d, and DEMs such as fumaric acid, L-lactic acid, 4-hydroxynonenal, and acetylvalerenolic acid. These DEGs and DEMs may play a role in the modulation of glucolipid metabolic pathways. In conclusion, our results suggest that gestational exposure to PFBS may induce molecular perturbations in glucose homeostasis. These findings provide insights into the potential mechanisms contributing to the heightened risk of abnormal glucose tolerance associated with PFBS exposure.

Engineering a transposon-associated TnpB-ωRNA system for efficient gene editing and phenotypic correction of a tyrosinaemia mouse model.

Transposon-associated ribonucleoprotein TnpB is known to be the ancestry endonuclease of diverse Cas12 effector proteins from type-V CRISPR system. Given its small size (408 aa), it is of interest to examine whether engineered TnpB could be used for efficient mammalian genome editing. Here, we showed that the gene editing activity of native TnpB from Deinococcus radiodurans (ISDra2 TnpB) in mouse embryos was already higher than previously identified small-sized Cas12f1. Further stepwise engineering of noncoding RNA (ωRNA or reRNA) component of TnpB significantly elevated the nuclease activity of TnpB. Notably, an optimized TnpB-ωRNA system could be efficiently delivered in vivo with single adeno-associated virus (AAV) and corrected the disease phenotype in a tyrosinaemia mouse model. Thus, the engineered miniature TnpB system represents a new addition to the current genome editing toolbox, with the unique feature of the smallest effector size that facilitate efficient AAV delivery for editing of cells and tissues.

Dietary and maternal sociodemographic determinants of perfluoroalkyl and polyfluoroalkyl substance levels in pregnant women.

Diet, including drinking water, and demographic characteristics have been associated with PFAS exposure levels in the general population. But data in pregnant women are scarce. We aimed to examine the PFAS levels in relation to these factors in early pregnancy and included 2545 pregnant women in early pregnancy from the Shanghai Birth Cohort. Ten PFAS were measured using high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS-MS) in plasma samples at around 14 weeks of gestation. Geometric mean (GM) ratios were used to estimate the associations between demographic characteristics, food intake and source of drinking water and concentrations of nine PFAS with a detection rate of at least 70%, and the total perfluoroalkyl carboxylic acids (∑PFCA), perfluoroalkyl sulfonic acids (∑PFSA) and all the PFAS concentrations (∑PFAS). Median concentrations of plasma PFAS ranged from 0.03 ng/mL for PFBS to 11.56 ng/mL for PFOA. In the multivariable linear models, maternal age, parity, parental education level, marine fish, freshwater fish, shellfish, shrimps, crabs, animal kidneys, animal liver, eggs, and bone soup in early pregnancy were positively associated with plasma concentrations of certain PFAS. Whereas pre-pregnancy BMI, plant-based foods, and drinking bottled water were negatively associated with some PFAS concentrations. In summary, this study suggested that fish and seafood, animal offal, and high-fat foods (eggs and bone soup) were significant sources of PFAS. PFAS exposure may be reduced by consuming more plant-based foods and potential interventions, such as drinking water treatment.

Risk Factors for Symptomatic Recurrence after Laparoscopic Adenomyomectomy: A 3-Year Follow-up.

STUDY OBJECTIVE: To identify the clinical risk factors for symptomatic recurrence of adenomyosis after laparoscopic adenomyomectomy with a three-year follow-up. DESIGN: Retrospective study. SETTING: University-affiliated hospital. PATIENTS: A total of 149 patients were included in this study, including 52 patients with symptomatic recurrence and 97 without recurrence. INTERVENTION: Laparoscopic adenomyomectomy was performed first. MEASUREMENTS AND MAIN RESULTS: General clinical data, including preoperative, intraoperative, and postoperative indices, symptomatic recurrence, and follow-up information, were collected. Comparison of women with and without symptomatic recurrence revealed significant differences for age at surgery (p = .026), presence of concomitant ovarian endometrioma (p <.001), and prescription of postoperative hormonal suppression (yes/no) (p <.0001). A Cox proportional hazard model indicated that concomitant ovarian endometrioma was a significant risk factor for recurrence (hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.10-3.85, p = .001). Patients who received postoperative hormonal suppression had a lower risk of recurrence than those without hormonal suppression (HR, 0.30; 95% CI, 0.16-0.55, p <.0001). Those aged ≥40 years also had a lower risk of symptomatic recurrence than those <40 years (HR, 0.46; 95% CI, 0.24-0.88, p = .03). CONCLUSIONS: Concomitant ovarian endometrioma is a risk factor for symptomatic recurrence of adenomyosis after laparoscopic adenomyomectomy. Postoperative hormonal suppression and older age at surgery (≥40 years) are protective factors.

Paraben exposure and couple fecundity: a preconception cohort study.

STUDY QUESTION: Is pre-conception exposure to parabens associated with fecundity in couples of childbearing age? SUMMARY ANSWER: Paraben exposure in female partners was associated with reduced couple fecundity and anti-Müllerian hormone (AMH) might be one of the possible mediators. WHAT IS KNOWN ALREADY: The reproductive toxicity of parabens, a class of widely used preservatives, has been suggested but evidence regarding their effects on couple fecundity is scarce. STUDY DESIGN, SIZE, DURATION: In this couple-based prospective cohort study, a total of 884 pre-conception couples who participated in the Shanghai Birth Cohort between 2013 and 2015 were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: Concentrations of six parabens were measured in urine samples collected from couples. Malondialdehyde, C-reactive protein, and AMH were assessed in female partners. The outcomes included couple fecundability (time-to-pregnancy, TTP) and infertility (TTP > 12 menstrual cycles). Partner-specific and couple-based models were applied to estimate the associations. The joint effect of paraben mixture on couple fecundity was estimated by quantile-based g-computation (q-gcomp). Mediation analysis was used to assess the mediating roles of oxidative stress, inflammation and ovarian reserve. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 525 couples (59.4%) conceived spontaneously. In the partner-specific model, propyl paraben (PrP), butyl paraben (BuP), and heptyl paraben (HeP) in female partners were associated with reduced fecundability (fecundability odds ratio (95% CI): 0.96 (0.94-0.98) for PrP; 0.90 (0.87-0.94) for BuP; 0.42 (0.28-0.65) for HeP) and increased risk of infertility (rate ratio (95% CI): 1.06 (1.03-1.10) for PrP; 1.14 (1.08-1.21) for BuP; 1.89 (1.26-2.83) for HeP). Similar associations were observed in the couple-based model. AMH played a significant mediation role in the association (average causal mediation effect (95% CI): 0.001 (0.0001-0.003)). Paraben exposure in male partners was not associated with couple fecundity. The joint effect of paraben mixture on couple fecundity was non-significant. LIMITATIONS, REASONS FOR CAUTION: Self-reported pregnancy and single urine sample may lead to misclassification. The mediation analysis is limited in that levels of sex hormones were not measured. The inclusion of women with irregular menstrual cycles might affect the results. It is possible that the observed association was due to reverse causation. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to assess the effects of paraben exposure on couple fecundity in Asians. Given the widespread exposure to parabens in couples of childbearing age, the present findings may have important public health implications. STUDY FUNDING/COMPETING INTEREST(S): This study was supported in part by the National Natural Science Foundation of China (41991314), the Shanghai Science and Technology Development Foundation (22YF1426700), the Science and Technology Commission of Shanghai Municipality (21410713500), and the Shanghai Municipal Health Commission (2020CXJQ01). All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Associations between urinary monohydroxylated polycyclic aromatic hydrocarbons and unexplained recurrent spontaneous abortion and health risk assessment in a large case-control study in China.

Polycyclic aromatic hydrocarbons (PAHs) are a group of environmental endocrine disruptors with known carcinogenic, reproductive, and developmental toxicity. Important knowledge gaps remain regarding the relationship between PAH exposure and unexplained recurrent spontaneous abortion (URSA). In the present study, twelve monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) were measured in the urine of 413 URSA cases and 434 controls. The main OH-PAHs measured in this study were monohydroxy metabolites of naphthalene, followed by fluorene and phenanthrene. After the creatinine correction, the median concentration of urinary OH-PAHs in the control group (17.4 µg/g Creatinine) was higher than that in the case group (14.2 µg/g Creatinine). There was no positive relationship between PAH exposure and URSA using binary logistic regression analysis. Among 847 Chinese women of childbearing age, residential environment, type of drinking water, and education level were the influencing factors of PAH exposure. The health risk assessment showed that over 98% of women had a carcinogenic risk with carcinogenic risk values above the acceptable level (10-6). Although this large-scale case-control study did not observe an association between PAH exposure and URSA, more attention should be paid to the high carcinogenic risk due to PAH exposure in women of reproductive age.

Prophylactic antibiotic use during labor and delivery in China: a nationwide, multicenter, hospital-based, cross-sectional study.

BACKGROUND: Prophylactic antibiotic use during delivery is common in routine obstetric practice to prevent infection globally, especially in low- and middle-income countries. In China, however, little is currently known about the national estimates for prophylactic antibiotic use during delivery. Therefore, we aimed to describe the prevalence of prophylactic antibiotic use and guideline adherence using national data in China. METHODS: This cross-sectional study analyzed a national dataset from the China Labor and Delivery Survey in 2015-2016. The primary outcomes were prophylactic antibiotic use and clinician adherence to WHO recommendations for the prevention and treatment of maternal peripartum infections. We estimated the weighted prevalence of the outcomes with Taylor series linearization and investigated the associated factors of the outcomes with logistic regression. RESULTS: Of the 72,519 deliveries, the prevalence of antibiotic prophylaxis was 52.0%, varying from 92.8% in Shanxi to 17.3% in Hainan. The prevalence of clinician adherence to the WHO guideline was 79.9%, ranging from 93.4% in Shandong to 50.0% in Shanxi. Prophylactic antibiotic use was associated with cesarean delivery (AOR, 55.77; 95%CI, 25.74-120.86), operative vaginal delivery (AOR, 4.00; 95%CI, 1.64-9.78), preterm (AOR, 1.96; 95%CI, 1.60-2.41), premature rupture of membranes (PROM) (AOR, 2.80; 95%CI, 1.87-4.18), and meconium-stained amniotic fluid (AOR, 1.91; 95%CI, 1.30-2.81) in all deliveries and also episiotomy (AOR, 1.48; 95%CI, 1.02-2.16) in vaginal deliveries. Clinician adherence was positively associated with cesarean delivery (AOR, 5.72; 95%CI, 2.74-11.93) while negatively associated with operative vaginal delivery (AOR, 0.26; 95%CI, 0.11-0.61), PROM (AOR, 0.50; 95%CI, 0.35-0.70), and meconium-stained amniotic fluid (AOR, 0.66; 95%CI, 0.48-0.91) in all deliveries. In vaginal deliveries, clinician adherence was negatively associated with episiotomy (AOR, 0.67; 95%CI, 0.46-0.96) and severe perineal trauma (AOR, 0.09; 95%CI, 0.02-0.44). Besides, clinicians in general hospitals prescribed prophylactic antibiotics more likely (AOR, 2.79; 95%CI, 1.50-5.19) and had a lower adherence (AOR, 0.38; 95%CI, 0.20-0.71) than their peers in maternity hospitals. CONCLUSIONS: We observed that about half of all deliveries in China received antibiotics for prophylaxis, and most deliveries were prescribed according to the WHO guideline. Furthermore, the two prevalence rates for prophylactic antibiotic use and clinician adherence varied widely across provinces of China.

Exposure to perfluoroalkyl substances and neurodevelopment in 2-year-old children: A prospective cohort study.

BACKGROUND: Humans are widely exposed to per- and polyfluoroalkyl substances (PFAS). As fetal stage is a critical window for neurodevelopment, it is important to know if in utero exposure to PFAS affects fetal neurodevelopment. However, previous human studies are both limited and inconsistent. OBJECTIVES: To investigate the relationship between PFAS exposure during early pregnancy and the neurodevelopmental status at 2 years of age in a prospective cohort study. METHODS: We measured 10 PFAS in maternal plasma samples collected prior to 16 weeks of gestation in the Shanghai Birth Cohort Study between 2013 and 2016. Childhood neurodevelopment was assessed at 2 years of age using the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Associations with domain specific scores for individual PFAS were assessed by multiple linear regression and binary logistic regression when scores were dichotomized. Quantile-based g-computation was used to estimate the joint effects of PFAS mixture. RESULTS: A total of 2257 mother-child pairs who had both PFAS and BSID measurements were included in our analyses. The means and standard deviations of comprehensive scores were 115 ± 22, 96 ± 15 and 108 ± 15 for cognition, language, and motor, respectively. In multiple linear regressions, we observed significant negative associations of perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluoroundecanoic acid (PFUnDA) with cognitive scores; PFNA, PFDeA, PFUnDA and perfluorohexanesulfonate (PFHxS) negatively with language scores; and PFNA and PFUnDA negatively with motor scores. Quantile-based g-computation showed that PFAS mixture was significantly associated with decreased cognitive and language scores, with an estimated ß of -2.1 [95% confidence interval (CI): -3.5, -0.7)] and -2.0 (95% CI: -2.9, -1.0) per one quartile increase in PFAS mixture for cognitive and language domains, respectively. PFAS mixture was associated with increased odds of low cognition (adjusted odds ratio [OR] = 1.3, 95% CI:1.0, 1.6) and language scores (OR = 1.2, 95% CI: 1.1, 1.3). CONCLUSIONS: PFAS exposure during early pregnancy was significantly associated with the adverse neurodevelopmental status at 2 years of age, which raises a serious public health concern.

Association of emerging and legacy per- and polyfluoroalkyl substances with unexplained recurrent spontaneous abortion.

Emerging per- and polyfluoroalkyl substances (PFAS) alternatives are increasingly used in daily life. Although legacy PFAS have been associated with miscarriage in previous studies, it remains unknown whether exposure to emerging and legacy PFAS has any impact on the risk of unexplained recurrent spontaneous abortion (URSA). We conducted a case-control study with 464 URSA cases who had at least 2 unexplained miscarriages and 440 normal controls who had at least one normal livebirth. Concentrations of 21 PFAS in plasma, including three emerging PFAS alternatives, eight linear and branched PFAS isomers, four short-chain PFAS, and six legacy PFAS, were measured by ultra-performance liquid chromatography coupled with a tandem mass spectrometry (UPLC-MS/MS). Multiple logistic regression was applied to evaluate the relationship between PFAS and URSA risk. Perfluorooctanoic acid (PFOA, median: 6.18 ng/mL), perfluorooctane sulfonate (PFOS, median: 4.10 ng/mL), and 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA, median: 2.27 ng/mL) were the predominant PFAS in the controls. Exposure to 6:2 Cl-PFESA [adjusted odds ratio (aOR) = 1.18 (95% CI: 1.00, 1.39)] and hexafluoropropylene oxide dimer acid (HFPO-DA) [aOR = 1.35 (95% CI: 1.15, 1.59)] were significantly associated with increased risks of URSA. Women with older age (>30 years old) had a stronger association between PFAS and URSA. Our results suggest that emerging PFAS alternatives may be an important risk factor for URSA.

Levels and health risks of urinary phthalate metabolites and the association between phthalate exposure and unexplained recurrent spontaneous abortion: a large case-control study from China.

Phthalate acid esters (PAEs) are environmental endocrine disruptors that can interfere with endocrine processes and cause adverse reproductive outcomes. The link between PAE exposure and unexplained recurrent spontaneous abortion (URSA) remains unknown. In this study, nine urinary metabolites of PAEs (mPAEs) were measured in 594 URSA cases and 569 healthy controls. The measured mPAEs were ubiquitously detected and present at higher levels (median: 203 ng/mL) in the URSA cases than in the controls (median: 161 ng/mL). Multiple logistic regression analysis showed that URSA was associated with higher concentrations of mono (2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), mono (2-ethylhexyl) phthalate (mEHP), and mono-ethyl phthalate (mEP) and lower concentrations of mono-isobutyl phthalate (miBP). Moreover, a quantile-based g-computation (QGC) model revealed a positive association between mPAEs mixture and URSA. The URSA cases showed significantly higher concentrations of di-(2-ethylhexyl) phthalate (DEHP) than the controls. This was consistent with the health risk assessment, which suggested that DEHP is the main contributors to potential non-carcinogenic risk. DEHP accounted for over 80% of total risk. The large case-control study results suggest that PAE exposure may increase the risk of URSA, and that policy-makers and public health experts should pay more attention to DEHP exposure.

Environmental exposure to bisphenol analogues and unexplained recurrent miscarriage: A case-control study.

The use of bisphenol A (BPA) has been substantially limited since 2010 due to its toxicity to human health. A group of bisphenol analogues that are structurally similar to BPA have been developed as the alternatives and used widely. The reproductive toxicity of these emerging chemicals has caused substantial concerns in recent years. Whether bisphenol analogues affect miscarriage, especially unexplained recurrent miscarriage (URM), remains to be explored. We conducted a hospital-based, case-control study with 1180 URM cases and 571 controls in China from 2014 to 2016. Concentrations of six bisphenol analogues (BPA, BPAF, BPAP, BPB, BPP and BPS) were measured in the urine samples collected at median intervals of 7.6 months after last miscarriage (interquartile ranges: 4.8, 14.7 months). Multiple logistic regression, Bayesian kernel machine regression (BKMR) and quantile g-computation (q-gcomp) were used to assess the relationship of bisphenol analogues with URM risk. We observed significantly higher levels of all urinary bisphenols in the cases than the controls. After controlling for potential confounders, bisphenol analogues were significantly associated with increased odds of URM in varying degrees. A dose-response pattern was observed for the associations of BPAF, BPAP and BPB quartiles with URM. The mixed exposure of six bisphenol analogues was positively associated with the risk of URM (adjusted odds ratio (aOR) = 1.25; 1.11-1.42), which was mainly driven by BPAP (60.1%), BPAF (25.1%) and BPA (14.8%). After age stratification, the risks tended to be higher in women aged 30 years or older, compared to women <30 years. Our large case-control study indicates that environmental exposure to bisphenol analogues is associated with an increased risk of URM. Older women may be more vulnerable to the insult.

Association between halitosis and female fecundability in China: a prospective cohort study.

BACKGROUND: Periodontal diseases and poor oral hygiene are potentially associated with decreased female fecundability. Fecundability refers to the probability of conception during a given period measured in months or menstrual cycles. This study aims to examine whether halitosis is associated with female fecundability in a large sample of Chinese women who planned to be pregnant. METHODS: In 2012, a total of 6319 couples came for preconception care in eight districts in Shanghai, China and were followed by telephone contact. Three thousand nine hundred fifteen women who continued trying to be pregnant for up to 24 months remained for final statistical analyses. Halitosis was self-reported at the preconception care visit. Time to pregnancy (TTP) was reported in months and was censored at 24 months. Fecundability ratio (FR) was defined as the ratio of probability of conception among those with and without halitosis. FR and 95% confidence interval (CI) were estimated using the discrete-time Cox model. RESULTS: 80.1 and 86.1% of women had self-reported clinically confirmed pregnancy within 12 and 24 months, respectively. Halitosis was reported in 8.7% of the women. After controlling for potential confounders, halitosis was associated with a reduced probability of spontaneous conception (for an observation period of 12 months: adjusted FR 0.82, 95% CI 0.72-0.94; for an observation period of 24 months: adjusted FR 0.84, 95% CI 0.74-0.96). CONCLUSIONS: Halitosis is associated with reduced fecundability in Chinese women.

Coordination of two enhancers drives expression of olfactory trace amine-associated receptors.

Olfactory sensory neurons (OSNs) are functionally defined by their expression of a unique odorant receptor (OR). Mechanisms underlying singular OR expression are well studied, and involve a massive cross-chromosomal enhancer interaction network. Trace amine-associated receptors (TAARs) form a distinct family of olfactory receptors, and here we find that mechanisms regulating Taar gene choice display many unique features. The epigenetic signature of Taar genes in TAAR OSNs is different from that in OR OSNs. We further identify that two TAAR enhancers conserved across placental mammals are absolutely required for expression of the entire Taar gene repertoire. Deletion of either enhancer dramatically decreases the expression probabilities of different Taar genes, while deletion of both enhancers completely eliminates the TAAR OSN populations. In addition, both of the enhancers are sufficient to drive transgene expression in the partially overlapped TAAR OSNs. We also show that the TAAR enhancers operate in cis to regulate Taar gene expression. Our findings reveal a coordinated control of Taar gene choice in OSNs by two remote enhancers, and provide an excellent model to study molecular mechanisms underlying formation of an olfactory subsystem.

Programmable RNA editing with compact CRISPR-Cas13 systems from uncultivated microbes.

Competitive coevolution between microbes and viruses has led to the diversification of CRISPR-Cas defense systems against infectious agents. By analyzing metagenomic terabase datasets, we identified two compact families (775 to 803 amino acids (aa)) of CRISPR-Cas ribonucleases from hypersaline samples, named Cas13X and Cas13Y. We engineered Cas13X.1 (775 aa) for RNA interference experiments in mammalian cell lines. We found Cas13X.1 could tolerate single-nucleotide mismatches in RNA recognition, facilitating prophylactic RNA virus inhibition. Moreover, a minimal RNA base editor, composed of engineered deaminase (385 aa) and truncated Cas13X.1 (445 aa), exhibited robust editing efficiency and high specificity to induce RNA base conversions. Our results suggest that there exist untapped bacterial defense systems in natural microbes that can function efficiently in mammalian cells, and thus potentially are useful for RNA-editing-based research.

Variation in alarm calls during different breeding stages of the common kestrel (Falco tinnunculus).

Acoustic signals play a key role in animal communication. Animals usually use alarm signals to warn mates or offspring of the presence of threats or to intimidate or distract predators. Birds commonly use acoustic signals as a means of communication. Alarm calls in passerines at different breeding stages can reflect their nest defense intensity. However, little is known about the characteristics, plasticity, and impact factors of alarm calls during the reproductive period in raptors. Here, from March to July in 2019, the alarm calls of eight pairs of common kestrels (Falco tinnunculus) during the breeding period were recorded using a portable recorder with a strongly directed microphone in the Zuojia Nature Reserve, Jilin province, China. The differences in acoustic parameters of parental alarm calls in different breeding stages were analyzed. The results showed that the alarm calls of common kestrels were composed of multi-harmonic arched frequency modulation with the maximum energy distribution in the second harmonic. The duration and rate of the alarm calls increased significantly as the breeding season progressed, showing that parents spent increasing amounts of time on nest defense. Additionally, the acoustic parameters of alarm calls in common kestrels were significantly different depending on offspring numbers, suggesting that offspring numbers influenced parental nest defense. These results showed that differences in alarm calls during different breeding stages may reflect a trade-off between defense costs and reproductive benefits.

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances and birth outcomes: A longitudinal cohort with repeated measurements.

BACKGROUND: Previous studies on perfluoroalkyl and polyfluoroalkyl substances (PFAS) showed inconsistent results when biological samples were collected in different time of pregnancy. OBJECTIVES: To describe the change of PFAS concentration during pregnancy and to identify a sensitive window for adverse effects of PFAS on the fetus. METHODS: A total of 255 pregnant women were selected from the Shanghai Birth Cohort (SBC). We quantified 10 PFAS with high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) in maternal plasma at three trimesters and cord blood at delivery. Multiple linear regression analyses were used to analyze the association between PFAS and birth outcomes, including birth weight, birth length, and head circumference. RESULTS: The concentrations of most PFAS declined substantially during pregnancy. PFOS, PFNA, PFDA, PFUA and PFDoA were negatively related to birth length only in the first trimester. The coefficients and 95% confidence intervals (CI) of birth length change with a log-unit increase in PFOS, PFNA, PFDA, PFUS and PFDoA concentrations were -0.27 cm (-0.51, -0.02), -0.34 cm (-0.65, -0.03), -0.27 cm (-0.53, -0.01), -0.29 cm (-0.58, -0.01), and -0.54 cm (-1.00, -0.08), respectively. The effects were only observed for female fetuses. No association between PFAS and birth weight or head circumference was observed. CONCLUSION: The concentrations of most PFAS in the maternal circulation declined during pregnancy. There were negative associations between several PFAS and birth length. The sensitive window of exposure appeared to be the first trimester. The association was stronger for female fetuses.

Association of bisphenol A or bisphenol S exposure with oxidative stress and immune disturbance among unexplained recurrent spontaneous abortion women.

Human exposure to environmental chemicals might play a role in the pathogenesis of unexplained recurrent spontaneous abortion (URSA). Bisphenol A (BPA) and bisphenol S (BPS) have been suggested to affect reproductive health. However, the mechanism remains unclear. To explore the association between BPA and BPS exposure and oxidative stress and immune homeostasis, we conducted a cross-sectional study and revealed BPA and BPS levels in relation to these two factors which were supposed to be implicated in miscarriage. 111 URSA patients were recruited and we analyzed urinary BPA and BPS concentrations, oxidative stress biomarkers (8-hydroxydeoxyguanosine and 8-isoprostane) and serum immune balance biomarkers (IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α, TGF-ß and IFN-γ). Multivariable linear regression models were used to evaluate the correlation between bisphenols exposure and outcome biomarkers. After adjustment for age, BMI, menstrual cycle, and parity history, creatinine-adjusted BPA was significantly associated with increases in 8-isoprostane (ß = 0.74, 95% CI = 0.07, 1.41; p = 0.031) and IFN-γ (ß = 0.18, 95% CI = 0.00, 0.36; p = 0.046). No statistical correlation between BPS and biomarkers of oxidative stress or immune balance was observed when all participants were analyzed. Further analysis revealed that in the subgroup of BPS > limit of detection (0.01 ng/ml), creatinine-adjusted BPS was significantly associated with increases in IL-10 (ß = 0.22, 95% CI = 0.00, 0.45; p = 0.048). Our findings suggested that BPA and BPS exposure might be related to oxidative stress and immune imbalance in URSA patients. Overall, our work might suggest potential pathogenic and aetiological associations among the bisphenols, biomarkers and URSA, which offers hypotheses for further studies.