Reproductive Toxicology

Polycystic Ovary Syndrome (PCOS), a multifaceted endocrine disorder, affects a significant proportion of women globally, with its etiology rooted in both genetic and environmental factors. This study delves into the environmental aspect, particularly focusing on the role of endocrine-disrupting chemicals (EDCs) in the context of urbanization and industrialization. This research examines the impact of endocrine-disrupting chemicals (EDCs) - Bisphenol A (BPA), Mono-ethyl Hexyl Phthalate (MEHP), and Di-ethyl Hexyl Phthalate (DEHP) - on 40 women with Polycystic Ovary Syndrome (PCOS) across urban and rural Gujarat...

The inhalation exposure to crude oil vapor (COV) has been shown to have adverse effects on the placenta and fetal development. The modulatory effects of quercetin (QUE) as a natural phenolic compound with antioxidant properties are promising for the protection of placental structure. This study aimed to investigate the modulatory role of QUE in mitigating histopathological damage, oxidative stress, and biochemical alteration in the placenta of COV-exposed pregnant rats. Forty-eight pregnant rats were divided into eight groups (days 15 and 20) as follows: 1-2) Control groups, 3-4) COV groups, 5-6) COV+QUE groups, and 7-8) QUE-treated groups (50mg/kg)...

Avobenzone (AVO), an ultraviolet (UV) filter, is frequently used as an ingredient in personal cosmetics. This UV filter has been found to be easily exposed in swimming pools and beaches, and it has been detected in human urine and blood. Moreover, numerous studies have demonstrated that AVO exhibits endocrine-disrupting properties. Nevertheless, the effects of AVO on male fertility have not yet fully understood. Therefore, this study aimed to assess the effects of AVO on various sperm functions during capacitation...

There is growing interest in establishing alternative methods in place of conventional animal tests to assess the developmental and reproductive toxicity (DART) of chemicals. Gastruloids are 3D aggregates of pluripotent stem cells that spontaneously exhibit axial elongation morphogenesis similar to gastrulation. They have been explored as in vitro embryogenesis models for developmental and toxicological studies. Here, a mouse gastruloid-based assay was validated for DART assessment in accordance with the ICH S5(R3) guideline, which provides the plasma concentration data of various reference drugs in rodents, specifically Cmax and AUC for NOAEL and LOAEL...

Tetra-amido macrocyclic ligands (TAMLs) are catalysts designed to mimic endogenous peroxidases that can degrade pollutants. Before TAMLs gain widespread use, it is first important to determine if they have endocrine disrupting properties. In this study, we evaluated the effects of the iron TAML, NT7, on hormone-sensitive outcomes in mice exposed during pregnancy and lactation, and on their litters prior to weaning. We administered NT7 at one of three doses to mice via drinking water prior to and then throughout pregnancy and lactation...

The aim of this study was to investigate the role of ferroptosis in fluorosis women and the in vitro molecular mechanisms leading to ovarian dysfunction and abnormal hormone secretion by sodium fluoride (NaF) treatment of KGN cells. Fifty women with fluorosis as Fluorosis group and fifty healthy women as Control group were included in this study. The levels of lipid peroxidation and activities of antioxidant enzyme were assessed by photometric methods. The content of iron and glutathione (GSH) in serum was measured by microplate method...

It is well known that the epididymis promotes post-testicular sperm maturation events. However, its malfunction during congenital hypothyroidism is relatively less understood as compared to the testis. The present study evaluated the probable effect of α-lipoic acid on epididymal oxidative stress parameters in rats exposed to antithyroid drug, carbimazole during fetal period. Time-mated pregnant rats in unexposed and carbimazole (1.35mg/Kg body weight exposed were allowed to deliver pups and weaned. At postnatal day 100, the F1 male pups were assessed for epididymal endpoints...

Cadmium (Cd) is a harmful environmental pollutant that disrupts public health, including respiratory, digestive, and reproductive systems. In this study, male rats were exposed to CdCl2 at a dose of 3mg/kg by oral for 28 days to investigate the impact on spermatogenesis. Testis tissue samples were collected after sacrifice, and piRNA expression levels were measured using piRNA microarray and qPCR. PiRNAs, specialized molecules involved in spermatogenesis, were examined. CdCl2 exposure led to disrupted piRNA expression, particularly in piRNA-DQ759395 in rats...

Fetal hepatic dimethylbenz(a)anthracene (DMBA) biotransformation is not defined, thus, this study investigated whether the fetal liver metabolizes DMBA and differs with biological sex. KK.Cg-a/a (lean; n = 20) or KK.Cg-Ay/J (obese; n = 20) pregnant mice were exposed to corn oil (CT) or DMBA (1mg/kg bw/day) by intraperitoneal injection (n = 10/treatment) from gestation day 7-14. Postnatal day 2 male or female offspring livers were collected. Total RNA (n = 6) and protein (n = 6) were analyzed via a PCR-based array or LC-MS/MS, respectively...

A widely used type II pyrethroid pesticide cypermethrin (CYP) is one of endocrine disrupting chemicals (EDCs) with anti-androgenic activity to induce male reproductive toxicology. However, the mechanisms have not been fully elucidated. This study was to explore the effects of CYP on apoptosis of mouse Sertoli cells (TM4) and the roles of endoplasmic reticulum (ER)-mitochondria coupling involving 1,4,5-trisphosphate receptor type1-glucose-regulated protein 75-voltage-dependent anion channel 1 (IP3R1-GRP75-VDAC1)...

Gestational exposure to the anticonvulsant drug valproic acid (VPA) is associated with congenital malformations and neurodevelopmental disorders through its action as a histone deacetylase inhibitor. VPA can elicit placental toxicity and affect placental growth and development. The objective of this study was to evaluate the impact of maternal exposure to VPA on the mouse placenta following exposure on gestational day (GD) 13 since previous studies have shown that mice exposed at this time during gestation give birth to offspring with an autism spectrum disorder-like phenotype...

Particulate matter 2.5 (PM2.5) is associated with reproductive health and adverse pregnancy outcomes. However, studies evaluating biological markers of PM2.5 are lacking, and identifying biomarkers for estimating prenatal exposure to prevent pregnancy complications is essential. Therefore, we aimed to explore urine metabolites that are easy to measure as biomarkers of exposure. In this matched case-control study based on the PM2.5 exposure, 30 high PM2.5 group (>15μg/m3 ) and 30 low PM2.5 group (<15μg/m3 ) were selected from air pollution on pregnancy outcome (APPO) cohort study...

The prepubertal period is crucial for sexual development and any alterations can interfere with the reproductive system in adulthood. The aim of this study was to evaluate how Benzo(a)pyrene (BaP) can affect the testes during the prepubertal period. Juvenile male Wistar rats were divided into a control (corn oil + DMSO) and a BaP-group (0.1μg/kg/day), exposed to BaP for 31 days (gavage), and all parameters were evaluated on postnatal day (PND) 54. Leukocyte counts were decreased. Histological analyses of the testes revealed that height and seminiferous tubules diameters (STDs) were reduced, tubular dynamics were altered, and Leydig cell atrophy was evident in the BaP-group...

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4-Nonylphenol (4-NP) is an endocrine-disrupting chemical that impairs animal and human reproduction. However, the mechanisms underlying male reproductive dysfunction by 4-NP have not been fully understood. Herein, we demonstrated the effects of 4-NP on boar sperm functions and molecular mechanisms. Spermatozoa were treated with various concentrations of 4-NP (0, 10, 25, 50, 75, and 100μM) during capacitation. Then, we evaluated sperm motility, capacitation status, intracellular ATP level, and cell viability...

The combined effects of air pollution and extreme temperature on PTB remain unclear. To evaluate the independent effect and interaction effect of prenatal extreme exposure to air quality index (AQI) and Humidex, on PTB. Based on the National Health Care Data Platform of Shandong University, women who gave birth in 2019-2020 were selected for the study. First, the independent effects of AQI and Humidex on PTB were assessed by logistic regression model. Subsequently, the interaction effects of AQI and Humidex on PTB were estimated separately by calculation of the relative excess risk of interaction (RERI)...

As the incidence of precocious puberty has risen in recent years and the age at puberty onset is younger, children may be at increased risk for health consequences associated with the early onset of puberty. Bisphenol A (BPA) is recognized as an endocrine disruptor chemical that is reported to induce precocious puberty. The effect of BPA exposure modes, times, and doses (especially low dose) were controversial. In the present study, we evaluated the potential effects of maternal exposure to low-dose BPA on the hypothalamus, particularly on the arcuate (ARC) nucleus and anteroventral periventricular (AVPV) nucleus during peri-puberty in offspring of BPA-treated rats...

A negative impact of finasteride on fertility has been reported, in which over production of reactive oxygen species and apoptosis were implicated. Hesperidin, a plant-derived bioflavonoid with antioxidant and anti-apoptotic effects, may mitigate these adverse effects. In order to investigate the possible protective role of hesperidin against finasteride-induced seminiferous tubules toxicity in adult male Wistar rats, 60 rats were randomized into five groups (I-V) receiving distilled water, 0.5% sodium carboxymethylcellulose solution, hesperidin, finasteride, and combined hesperidin and finasteride respectively...

This review summarizes data related to the potential importance of the ubiquitously functioning antioxidant, melatonin, in resisting oxidative stress and protecting against common pathophysiological disorders that accompany implantation, gestation and fetal development. Melatonin from the maternal pineal gland, but also trophoblasts in the placenta, perhaps in the mitochondria, produce this molecule as a hedge against impairment of the uteroplacental unit. We also discuss the role of circadian disruption on reproductive disorders of pregnancy...

Prenatal exposure to phthalates is common. However, its effect on birth weight has always been met with conflicting conclusions. To explore the effects of prenatal phthalate exposure on neonatal weight, we searched PubMed, Web of Science (WOS), Cochrane Library, and Embase databases for articles published up to October 24, 2023. Observational studies with 95% confidence intervals (CI) were included. Our findings indicate no significant association between either mixed exposure effects or single phthalate metabolites and offspring birth weight when monitoring maternal urine phthalate metabolites...