Pyridaben is an acaricide that inhibits mitochondrial complex I, which disrupts mitochondrial viability and causes oxidative stress. Pyridaben administration was associated with significant damage to mitochondrial DNA (mtDNA) in mice. The oxidative stress related to pyridaben exposure also co-occurred with alterations in the morphology of the testes and intestines, leading to the activation of the Nrf2-dependent protective pathway in testicular tissue, reduction of the seminiferous tubule lumen accompanied by interstitial tissue swelling, and adaptive changes in the intestinal epithelial tissue. Comenic acid (CA) exhibits active antioxidant properties; in the group receiving CA, the mtDNA copy number increased. Functionally, pyridaben considerably reduced the alpha diversity of the intestinal microbiome, while CA administration appeared to normalize this indicator, also mitigating shifts in beta diversity. Taxonomic analysis revealed that pyridaben elevated the abundance of the families Bacteroidaceae and Muribaculaceae, which aligned with a functional upregulation of endotoxic dTDP-β-L-rhamnose and L-lysine biosynthesis pathways. Conversely, CA treatment attenuated these shifts, reducing opportunistic taxa while concurrently upregulating protective pathways, including folate transformations and CDP-diacylglycerol biosynthesis. These findings suggest that CA, potentially due to its antioxidant properties and modulation of the intestinal microbial and functional profiles, may exert a compensatory effect against pyridaben-induced toxicity via the gut-testis axis.
Recurrent pregnancy loss (RPL), defined as two or more pregnancy failures, affects approximately 1-3% of reproductive-age couples worldwide. Despite advances in clinical evaluation, 50-60% of RPL cases remain unexplained, referred to as unexplained recurrent pregnancy loss (URPL), leaving a substantial proportion of patients without an identifiable etiology or evidence-based preventive strategies. Emerging evidence suggests that environmental exposures may represent an underrecognized yet modifiable contributor to URPL; however, the existing literature remains fragmented and methodologically flawed by the homogenization of pregnancy loss. This narrative review and critical gap analysis evaluates the epidemiological and mechanistic evidence linking a broad spectrum of environmental exposures to pregnancy loss. We systematically map the evidence base across ambient air pollutants, heavy metals, endocrine-disrupting chemicals, pesticides, and lifestyle/occupational hazards, with a strict focus on isolating URPL-specific data from general miscarriage cohorts. We further examine the principal biological mechanisms through which these exposures precipitate pregnancy loss, including oxidative stress, maternal immune dysregulation, epigenetic reprogramming, endocrine disruption, and placental vascular impairment. This critical gap analysis reveals that while environmental pollutants consistently increase the risk of sporadic pregnancy loss, URPL-specific evidence remains profoundly scarce. We highlight the urgent need to address the pervasive conflation of sporadic and recurrent loss in existing cohorts, call for future prospective studies prioritizing mixture-based exposures, and propose a forward-looking, non-judgmental framework for preconception wellness that mitigates the psychological burden on URPL patients.
The blood-testis barrier (BTB) is a specialized structure that maintains the testicular microenvironment and supports normal spermatogenesis. Preserving its structural integrity is critical for male reproductive function. In recent years, growing attention has been directed toward the adverse effects of exogenous toxicants, including environmental pollutants, nanomaterials, endocrine-disrupting chemicals (EDCs), and microplastics, on BTB integrity. Increasing evidence indicates that these toxicants impair the BTB through four major, interconnected mechanisms: (i) oxidative stress and disruption of antioxidant defenses; (ii) cytoskeletal remodeling and programmed cell death; (iii) endocrine disruption and hormonal imbalance; and (iv) metabolic dysfunction and abnormalities of the gut-testis axis. Moreover, simultaneous exposure to multiple pollutants often produces synergistic toxic effects, leading to more severe BTB damage. Despite substantial progress, the molecular regulatory networks underlying BTB injury remain incompletely understood, and targeted therapeutic strategies are still largely in the preclinical stage. This review systematically summarizes the structural organization and physiological functions of the BTB, comprehensively examines the mechanisms of toxicant-induced injury and their downstream reproductive consequences, and highlights recent advances in the field. We further discuss emerging BTB repair strategies, including antioxidant-based therapies, signaling pathway modulators, and targeted drug delivery systems. Finally, by critically evaluating current knowledge gaps and research challenges, this review establishes a comprehensive framework to advance fundamental research in male reproductive toxicology, facilitate the development of therapeutic interventions for BTB-related reproductive disorders, and ultimately support the protection and restoration of male reproductive health.
Valproic acid is used to treat epilepsy and Sodium Butyrate is emerging as an alternative treatment option. Though VPA and SB may affect male reproductive system, their possible intergenerational effects on male reproductive parameters is not known. We treated male rats with 10 or 20 mg/kg VPA or SB and evaluated the intergenerational effects on the male reproductive-related parameters. Male rats exposed to 10 or 20 mg/kg VPA or SB displayed reduced ability to induce pregnancy, produced lower litter size, marked by reduced litter weight; and these changes were observed in the next two generations. Sperm count, sperm motility and testosterone levels were reduced only in VPA-treated rats, which was also intergenerational. Oligospermia was evident in the caput and cauda of VPA-treated rats and in the subsequent generations. Results of this study provide preliminary evidence that using these two drugs for the treatment of epilepsy in males could affect reproductive outcomes in the progeny.
Bleomycin, commonly used in the treatment of various malignant tumors, has also been associated with gonadal toxicity and reduced fertility. This study aims to evaluate the effects of bleomycin on the male reproductive system. Twelve-week-old male rats were randomly divided into four groups: Control, B-0, B-60, and B-120. The treatment groups received 15 mg/kg of bleomycin intraperitoneally twice a week for three weeks. Following treatment, the rats were sacrificed on days 0, 60, and 120. Body weight and sperm concentration decreased significantly in the B-0 group compared to the control group, while they showed a partial increase in the B-60 and B-120 groups. Sperm DNA fragmentation was found to be significantly higher in the B-0 group compared to the control group, similar to the control group in the B-60 and B-120 groups. In the B-0 group, marked degeneration of the seminiferous tubules and thinning of the germinal epithelium were observed; the B-60 and B-120 groups improved to some extent. No significant differences were found between the groups in serum testosterone, MDA, and TAS levels, or in the expression levels of the Bax, Bcl2, Caspase-3, HO-1, iNOS, and Nrf2 genes. While NO levels increased in the B-0 group, they decreased to levels similar to those of the control group in the B-60 and B-120 groups. In conclusion, bleomycin causes significant but largely reversible damage to the male reproductive system, particularly affecting sperm parameters and testicular histology. However, the absence of fertilization and pregnancy assessment should be considered when interpreting the findings.
Abamectin (ABM) is a macrocyclic lactone insecticide that induces oxidative stress and testicular toxicity, but its specific effects on male reproductive function remain unclear. Here, we tested whether an aqueous extract of Salvia officinalis (S. officinalis) could mitigate ABM-induced testicular injury in adult male rats, focusing on mitochondrial fusion and apoptosis. Thirty-six rats were divided into six groups: control, S. officinalis extract (100 mg/kg), low-dose ABM (0.5 mg/kg), high-dose ABM (1 mg/kg), S. officinalis + low-dose ABM, and S. officinalis + high-dose ABM, for 70 days. Our results showed that the extract was rich in total phenolics and flavonoids. The main phenolic compounds were ferulic acid, syringic acid, caffeic acid, p-coumaric acid, and α-tocopherol, while the main flavonoids were luteolin, 2'-hydroxyflavone, apigenin, and quercetin. Rats exposed to ABM had lower sperm concentration and motility, more abnormal sperm, and markedly lower serum levels of testosterone, luteinizing hormone, and follicle-stimulating hormone in a dose-dependent manner. Furthermore, testicular malondialdehyde and nitric oxide levels increased, whereas catalase activity, glutathione levels, and the activities of superoxide dismutase and glutathione S-transferase decreased. Gene expression analysis showed reduced mitofusin-1 and mitofusin-2 and increased p53 and caspase-9 expression. Notably, co-administration of S. officinalis with ABM improved sperm quality, hormone levels, antioxidant status, gene expression, and testicular tissue structure. Our findings highlight the protective mechanisms of S. officinalis, including enhancing antioxidant defenses, promoting mitochondrial fusion, and inhibiting the intrinsic apoptotic pathway. These results suggest that the S. officinalis extract could have therapeutic potential for ABM-induced male reproductive toxicity.
INTRODUCTION:If taken during pregnancy, some psychotropic medications may increase the risk of adverse perinatal outcomes, including reduced birth weight and small for gestational age outcome. A key factor in foetal growth and development is the placental endocrine function, with critical placental hormones including human chorionic gonadotropin (hCG), placental growth factor (PlGF), and leptin. In this in vitro study, we aimed at characterising the impact of psychotropic medications on placental endocrine function. METHODS:We focused on often used psychotropic medications at concentrations up to 30 µM and including concentrations attained in blood plasma in (non-pregnant) patients. Their effects on the secretion of hCG, PlGF, and leptin were investigated in a well-established model of human trophoblasts (BeWo cells). Since intact cell viability and metabolic activity are required for hormone production, these aspects were studied beforehand. RESULTS:Citalopram (at 30 µM), sertraline and aripiprazole (at ≥10 µM) markedly reduce cell viability, whereas quetiapine (at 30 µM) slightly decreases it and diazepam and zolpidem (each up to 30 µM) do not affect it. Experiments with subtoxic concentrations of the medications reveal no effects on either metabolic activity or on the production of the hormone hCG. The production of PlGF varies slightly and depending on the medication tested. Diazepam and quetiapine (at 30 µM) markedly impair leptin production. DISCUSSION:Our findings reveal marked differences in how various medications affected cell viability and hormone production. Whether these effects could be related to changes in clinical outcomes such as birth weight and small-for-gestational-age requires further investigation.
Microplastics and nanoplastics are ubiquitous across global environments and can bioaccumulate through food chains, arousing concerns over their links to rising rates of male infertility. Relevant literature was retrieved from PubMed, Web of Science Core Collection and Scopus, and eligible original human, animal and cell studies were screened and analyzed. Epidemiological data confirm microplastic accumulation in human reproductive tissues, which correlates with declining semen quality. Experimental evidence reveals that microplastics penetrate the blood-testis barrier to trigger testicular oxidative stress, DNA damage and epigenetic dysregulation, further causing inflammation, barrier disruption, hormone imbalance and sustained spermatogenic injury. This review systematically interprets core toxic cascades of microplastic-induced male infertility, and compares heterogeneous reproductive toxicity from varying particle sizes, polymers, doses and combined pollutants. Research gaps and future directions are also outlined, providing theoretical support for assessing male reproductive hazards of microplastic pollution.
Whether PM2.5-induced spermatocyte injury engages the cGAS-STING innate immune pathway remains unknown. This study integrated network pharmacology, GEO transcriptomic profiling (GSE189187), gene set enrichment analysis, molecular docking with positive-control benchmarking, single-cell RNA sequencing, and in vitro validation in GC-2 spermatocyte cells to address this question. Among 35 overlapping candidates between 447 AS-IV putative targets and 102 cGAS-STING/inflammation genes, Hmox1 was the sole gene significantly upregulated by PM2.5 (log₂FC = 2.15, AUC = 1.000). KEGG analysis identified six enriched innate immunity pathways, with the Cytosolic DNA-sensing pathway at adjusted P = 8.1 × 10⁻⁶. Molecular docking demonstrated that AS-IV bound cGAS (-10.2 kcal/mol) and STING (-11.3 kcal/mol) with affinities exceeding known inhibitors G150 (-8.8) and H-151 (-8.6). In GC-2 cells, PM2.5 (200 μg/mL) increased ROS 5.35-fold, elevated apoptosis to 42.83%, and activated cGAS-STING signaling. AS-IV co-treatment restored viability to 83.3%, enhanced proliferation to 37.96%, significantly suppressed cGAS/p-TBK1/p-IRF3, and activated Nrf2/HMOX1 (HMOX1 protein 1.99 ± 0.05-fold; mRNA 6.44-fold), reducing apoptosis to 18.27%, ROS, and LDH release, and normalizing the Bax/Bcl2 ratio from 5.0 to 2.1. These findings establish that AS-IV protects spermatocytes through coordinated cGAS-STING suppression and Nrf2-dependent HMOX1 activation. Causal necessity of cGAS-STING activation was confirmed by RU.521-mediated pathway blockade, and direct AS-IV binding to cGAS (KD = 0.619 μM) and STING (KD = 0.097 μM) was validated by surface plasmon resonance.
Methotrexate (MTX) is a widely used chemotherapeutic and immunosuppressive agent; however, its clinical use is limited by severe testicular toxicity associated with oxidative stress, inflammation, apoptosis, and ferroptosis. Therefore, the present study investigated the protective effects of icariin-loaded nanoliposomal formulation (ICA-LNPs) against MTX-induced testicular injury in rats compared with crude icariin (ICA). Sixty adult male Sprague Dawley rats were randomly allocated into six groups: control, ICA, ICA-LNPs, MTX, MTX + ICA, and MTX + ICA-LNPs. MTX administration markedly impaired reproductive function, evidenced by significant reductions in testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sperm count, motility, and viability, together with increased sperm abnormalities. MTX also disrupted the NRF2/HO-1/NQO1 signaling pathway, suppressed antioxidant defenses, and elevated oxidative stress markers. In addition, MTX significantly activated NF-κB-mediated inflammatory responses, enhanced apoptotic and ferroptotic pathways, increased iron accumulation and ACSL4 expression, and reduced GPX4 and SLC7A11 expression in testicular tissue. Histopathological examination further confirmed severe degeneration of seminiferous tubules and impaired spermatogenesis. Treatment with ICA-LNPs significantly ameliorated these alterations and demonstrated superior protective efficacy compared with crude ICA. ICA-LNPs restored reproductive hormones, improved semen quality, enhanced antioxidant status, suppressed inflammatory mediators, reduced apoptosis and ferroptosis-related markers, and preserved normal testicular histoarchitecture. Furthermore, GPX4 immunoreactivity was markedly increased, whereas ACSL4 expression was significantly reduced following ICA-LNPs treatment. In conclusion, ICA-loaded nanoliposomal formulation effectively attenuated MTX-induced testicular toxicity and was associated with reduced oxidative stress, inflammation, apoptosis, and ferroptosis, highlighting its potential as a promising therapeutic strategy for preserving male reproductive function.
N-glycolylneuraminic acid (Neu5Gc), a dietary xenobiotic sialic acid acquired primarily from red meat and dairy products, cannot be synthesized by humans due to the inactivation of the CMAH gene. In contrast, its endogenous homologue N-acetylneuraminic acid (Neu5Ac) is abundant in human reproductive tissues. Although anti-Neu5Gc antibodies have been associated with infertility, the direct impact of free sialic acids on sperm function remains unclear. This study investigated the dose-dependent effects of physiologically relevant concentrations (0-10 μM) of Neu5Gc and Neu5Ac on human sperm function in vitro and elucidated the underlying mechanisms. After treatment, key sperm functions were comprehensively evaluated: motility by computer-assisted analysis, penetration capacity through methylcellulose, and acrosome reaction (AR) via chlorotetracycline staining. Sperm ATP concentration and mitochondrial membrane potential were evaluated by ELISA and JC-1. Intracellular Ca2 + levels and protein tyrosine phosphorylation were measured fluorometrically and by western blotting, respectively. Both Neu5Gc and Neu5Ac significantly and dose-dependently inhibited sperm total motility, progressive motility, penetration capacity, and both spontaneous and progesterone-induced AR. Neu5Gc and Neu5Ac compromised sperm ATP generation without impairing mitochondrial membrane potential. Mechanistically, these impairments were accompanied by a marked suppression of total protein tyrosine phosphorylation and a reduction in resting intracellular Ca2+ levels. In conclusion, our in vitro results demonstrate that free Neu5Ac and Neu5Gc, at physiologically relevant micromolar concentrations, impair essential sperm functions by disrupting capacitation-associated tyrosine phosphorylation and calcium signaling pathways, suggesting a possible diet-environment-reproductive health axis in male fertility.
Propylparaben is an antimicrobial preservative commonly found in consumer products. Recent studies suggest that it has endocrine-disrupting properties and may adversely affect female reproductive health. However, it remains unclear whether short-term propylparaben exposure affects the ovaries and oviducts of adult females. This study examined the effects of 10 days of exposure to environmentally relevant levels of propylparaben on selected genes, hormone levels, and protein expression in the murine ovary and oviduct. Adult CD-1 mice (n = 6/per group) were orally administered vehicle control (corn oil) or propylparaben at 20 μg/kg/day, 200 μg/kg/day, or 20 mg/kg/day by dispensing the dosing solution from a pipette tip into the oral cavity. After dosing, sera, ovaries, and oviducts were collected. Serum was used to measure progesterone and estradiol levels. Ovaries and oviducts were analyzed for the expression of steroidogenic regulators, apoptotic factors, antioxidant enzymes, epithelial cell markers, and estrogen receptor alpha. Differences between propylparaben-treated groups and controls were evaluated statistically. In the ovary, propylparaben selectively increased mRNA levels of Cyp17a1 (20 mg/kg/day), Cyp19a1 (20 mg/kg/day), and Bcl2 (20 and 200 μg/kg/day) compared with controls (p < 0.05). In the oviduct, propylparaben selectively increased mRNA levels of Bcl2 (20 and 200 μg/kg/day), Bax (all groups), and Gpx1 (20 mg/kg/day), and decreased protein levels of the ciliated cell marker acetylated-α-tubulin (20 μg/kg/day) compared with controls (p < 0.05). Last, hormone levels were similar across treatment groups (p > 0.05). These findings suggest that short-term propylparaben exposure alters key regulators in the ovary and oviduct, yet the broader implications for female reproductive health remain unclear.
Triptolide (TP), the principal bioactive component of Tripterygium wilfordii (T. wilfordii), exhibits potent pharmacological activities; however, its clinical application is limited by severe male reproductive toxicity, and effective interventions to mitigate reproductive toxicity remain limited. Although the relationship between ferroptosis and TP-induced male reproductive damage has garnered attention, it is still not fully understood whether intervening in ferroptosis can serve as a viable approach to ameliorate TP-induced testicular injury. Thus, this study aimed to characterize TP-induced ferroptosis in mouse testes and Sertoli cells and evaluate whether pharmacological inhibition of ferroptosis by liproxstatin-1 (Lip-1) could serve as a protective strategy against TP-induced testicular injury. In this study, we demonstrated that TP exposure caused significant testicular damage, characterized by pathological histological changes, disruption of the blood-testis barrier (BTB) integrity, a decrease in sperm count and motility, and an increase in sperm deformity. Mechanistically, TP downregulated key redox regulators (NRF2, HO-1, SLC7A11, and GPX4) and iron homeostasis proteins (FTH1, FTL, and FPN), implicating ferroptosis in male reproductive toxicity. Crucially, co-treatment with the Lip-1 effectively mitigated both BTB disruption and testicular damage induced by TP, both in vivo and in vitro. The protective effect was associated with the attenuation of lipid peroxidation and the restoration of the NRF2/HO-1/SLC7A11/GPX4 pathway. Collectively, our findings suggested that pharmacological inhibition of ferroptosis by Lip-1 represented a promising strategy against TP-induced BTB disruption and testicular injury.
Global sperm concentration has declined by over 50% in the past five decades, with environmental pollutants identified as a critical driving factor. This review focuses on testicular-level evidence regarding the effects of microplastics, bisphenol compounds, and air pollution on male reproductive health, with an emphasis on spermatogenic and testicular somatic cell mechanisms. Microplastics have been detected in human testicular tissue, with a causal pathway established linking gut microbiota dysbiosis, immune activation, and blood-testis barrier disruption. Bisphenol A substitutes show comparable or greater reproductive toxicity than BPA, with BCAT1-mediated ferroptosis identified as a novel testicular injury mechanism. For air pollution, spermatogenesis stage I (70-90 days prior to semen collection) has been pinpointed as the critical PM2.5 exposure vulnerability window, with metal constituents of traffic-derived PM2.5 as the primary toxicity drivers. Future research should prioritize prospective cohort studies and clinical intervention trials targeting these emerging mechanistic pathways.
The global decline in male fertility has emerged as a major public health challenge, with mounting evidence pointing to a close association between endocrine-disrupting chemicals (EDCs) and reproductive dysfunction. As a representative member of this class, dicyclohexyl phthalate (DCHP) exhibits strong environmental persistence and bioaccumulation potential within the mammalian reproductive system. In the present study, male ICR mice were orally administered DCHP at 10, 100, or 300 mg/kg/day for six consecutive weeks, and GC‑2 mouse spermatocyte cells were exposed to 5, 20, or 50 μM DCHP for 24 h. Long‑term, high‑dose DCHP exposure (300 mg/kg/day) was associated with significant testicular histopathological alterations and impaired epididymal sperm parameters in mice. Both the in vivo and in vitro models revealed that DCHP treatment correlated with cell cycle disruption and proliferative arrest. Western blotting and TUNEL assays further indicated that DCHP could triggered apoptosis. As an exploratory acute ex vivo assessment, 35 human semen samples were exposed to DCHP (5, 20 and 50 μM) for 12 h, which revealed a dose-dependent reduction in sperm quality. At the mechanistic level, our data suggest a potential cascade wherein DCHP exposure is linked to oxidative stress, concomitant DNA damage, and mitochondrial dysfunction. RNA‑seq analysis further highlighted the enrichment of inflammatory responses and related signaling pathways. Subsequent validation experiments showed that DCHP exposure was accompanied by an increased testicular M1 macrophage population, elevated secretion of pro‑inflammatory cytokines (IL‑6, TNF‑α), and activation of the NF‑κB pathway—changes that may collectively contribute to an unfavorable testicular microenvironment and impaired sperm quality. Overall, our findings reveal close associations between DCHP exposure and testicular injury, proposing a working model involving oxidative stress and inflammation; however, further functional studies are required to establish definitive causal relationships.
Background Studies have indicated that exposure to household pesticides is prevalent among the population. Nevertheless, the relationship and contributing factors linking urinary metabolites of household pesticides to circulating levels of sex steroid hormones in human serum remain insufficiently explored. Objective To examine the correlation between household pesticides metabolites and serum sex steroid hormones levels. Methods This study utilized data from 3884 participants obtained through the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. NHANES measured urinary metabolites of household pesticides and serum levels of sex steroid hormones. The study utilized weighted multiple linear regression modeling combined with restricted cubic spline (RCS) analysis to investigate relationships and dose-response patterns between residential pesticide metabolites and serum sex steroid hormones across both genders. Additionally, the research examined potential modifying effects of obesity status on pesticide metabolite-sex hormone associations through interaction analysis. Results Following adjustment for potential confounders, concentrations of 3,5,6-trichloro-2-pyridinol (TCPY), para-nitrophenol (PNP), and 3-phenoxybenzoic acid (3-PBA) demonstrated negative correlations with total serum testosterone (TT), estradiol concentrations(E2), and free androgen index (FAI) across all three statistical models (Ps < 0.05), while positive relationships emerged with sex hormone-binding globulin (SHBG). We found the similar results among male participants. However, the negative correlation was not found between TCPY, PNP, 3-PBA and SHBG among female participants RCS modeling revealed complex nonlinear interactions between DCBA and serum sex steroid hormone levels. Analysis stratified by body mass index showed that TCPY, PNP and 3-PBA exhibited similar negative correlations with TT, E2 and FAI in the non-obese participants. Conclusions The study reveals that the metabolites from household pesticides exhibited negative correlations with serum sex steroid hormone levels across both genders. Associations were more consistent for non-obese populations.
Zearalenone (ZEN) is a mycotoxin that widely contaminates human food supplies. In animal models, exposure to ZEN has extensive impacts on reproduction and pregnancy including contributing to early parturition. Here, we translate that research to humans by examining gestational exposure to ZEN in relation to the timing of birth and placental corticotropin releasing hormone (pCRH), a hormone that regulates the timing of parturition. Utilizing data from a pregnancy cohort (UPSIDE; Rochester, NY; n = 299), we investigated exposure to ZEN and its metabolites in relation to: 1) gestational age at birth; and 2) pCRH across pregnancy. Adjusted linear regression models were fitted to examine gestational age at birth and pCRH in relation to three maternal urinary mycoestrogen measures in each trimester: (1) ZEN; (2) its metabolite, α-zearalenol (aZOL); and (3) the sum of ZEN and its five metabolites (∑mycoestrogens). For models examining pCRH, we additionally fitted linear mixed effects models to account for repeated measures. All models were refitted stratified by fetal sex. Mycoestrogens were detected in over 90% of samples in each trimester. Sex-stratified analyses showed distinct sex differences in trimester 2 in relation to exposure, with higher gestational age at birth in males (β:2.35 days, 95%CI:0.14, 4.56) and lower gestational age at birth in females (β:-1.70 days, 95%CI:-3.35, -0.07). In linear mixed effects models examining pCRH, ZEN was positively associated with pCRH concentrations: ZEN (%Δ:5.17, 95%CI:1.09, 9.36). Mycoestrogen exposure may be associated with sex-specific changes in gestational age at birth and higher pCRH, a risk factor for preterm birth.
