Reproductive toxicology最新文献

Ethion is a class II moderately toxic organothiophosphate pesticide. The main objective of this study was to evaluate the maternal and foetal toxicity of ethion in rats. Pregnant rats were divided into 5 groups. Group I served as control. Group II, III, IV, and V were orally administered with 0.86, 1.71, 3.43, and 6.9 mg/kg of ethion respectively, from gestational day (GD) 6–19. Dams were sacrificed on GD 20. Maternal toxicity was assessed by body weight gain, foetal resorptions, oxidative stress, liver and kidney function tests, and histopathology. Foetal toxicity was assessed by physical status, gross, teratological and histopathological examination. Ethion caused dose-dependent reduction in maternal body weight gain, increased resorptions, and reduced gravid uterine weights. Elevated MDA levels and altered levels of GSH, SOD and catalase were recorded in pregnant dam serum and tissues. SGOT, SGPT, total bilirubin, urea, uric acid, and creatinine were elevated in ethion groups indicating liver and kidney toxicity. Histology of uterus revealed myometrial degeneration and mucosal gland atrophy in uterus of pregnant dams and degenerative changes in placenta. It showed histological alterations in liver, kidney, and lungs. There was reduction in the foetal body weights and placental weights, and degenerative changes in the foetal liver and kidney. Gross evaluation of foetuses showed subcutaneous hematoma. Skeletal evaluation showed partial ossification of skull bones, costal separation, and agenesis of tail vertebrae, sternebrae, metacarpals and metatarsals. The findings reveal that prenatal exposure to ethion caused maternal and foetal toxicity in rats.

Reproduction is a functional outcome that relies on complex cellular, tissue, and organ interactions that span the developmental period to adulthood. Thus, the assessment of its disruption by environmental chemicals would benefit significantly from scalable and innovative approaches to testing using functionally comparable reproductive models such as the nematode C. elegans. We adapted a previously described low-throughput in vivo chromosome segregation assay using C. elegans predictive of reproductive toxicity and leveraged available public data sources (ToxCast, ICE) to screen and characterize 133 physiologically-relevant chemicals in a high-throughput manner. The screening outcome was further validated in a second, independent in vivo assay assessing embryonic viability. In total, 13 chemicals were classified as reproductive toxicants with the two most active chemicals belonging to the large family of Quaternary Ammonium Compounds (QACs) commonly used as disinfectants but with limited available reproductive toxicity data. We compared the results from the C. elegans assay with ToxCast in vitro data compiled from 700+ cell response assays and 300+ signaling pathways-based assays. We did not observe a difference in the bioactivity or in the average potency (AC50) between the top and bottom chemicals. However, the intended target categories were significantly different between the classified chemicals with, in particular, an over-representation of steroid hormone targets for the high Z-score chemicals. Taken together, these results point to the value of in vivo models that scale to high-throughput level for reproductive toxicity assessment and to the need to prioritize the assessment of QACs impacts on reproduction.

Topiramate (TPM) is an antiepileptic drug used for treating epilepsy in children, and migraine in teenagers. In this context, preclinical studies with adult female rats observed reproductive system abnormalities following treatment with TPM. Additionally, exposure to endocrine disruptors during developmental plasticity periods, such as childhood and adolescence, may influence characteristics in the adult individual. This study evaluated whether treatment with TPM during developmental periods influences the reproductive system of female rats either immediately or in adult life. Female Wistar rats were treated with TPM (41 mg/Kg/day) by oral gavage from postnatal day (PND) 16–28, or PND 28–50, which correspond to childhood and adolescence, respectively, and euthanized either 24 h after the final administration or during adulthood. Treatment with TPM during adolescence induced short-term increase in uterus and ovary weights and reduction in endometrial stroma thickness. Adult animals treated during adolescence displayed reduced primordial ovarian follicles’ numbers, and increased primary and pre-antral ovarian follicles’ numbers. Treatment during childhood induced no short or long-term differences. These results indicate TPM treatment during adolescence is capable of inducing short and long-term alterations on the reproductive system of female Wistar rats.

Tripterygium glycosides (TG) is extracted from the roots of Chinese herbal medicine named Tripterygium wilfordii Hook F (TwHF). TG tablets are the representative TwHF-based agents with anti-inflammatory and immunomodulatory activities for treating rheumatoid arthritis. Although the curative effect of TG is remarkable, the clinical application is limited by a variety of organ toxicity. One of the most serious side-effects induced by TG is damage of the male reproductive system and the toxic mechanism is still not fully elucidated. TG-induced testicular injury was observed in male mice by treated with different concentrations of TG. The results showed that TG induced a significant decrease in testicular index. Pathological observation showed that spermatogenic cells were obviously shed, arranged loosely, and the spermatogenic epithelium was thin compared with control mice. In addition, the toxic effect of TG on mouse spermatogonia GC-1 cells was investigated. The results displayed that TG induced significant cytotoxicity in mouse GC-1 cells. To explore the potential toxic components that triggered testicular injury, the effects of 8 main components of TG on the viability of GC-1 cells were detected. The results showed that celastrol was the most toxic component of TG to GC-1 cells. Western blot analysis showed that LC3-II and the ratio of LC3-II/LC3-I were significantly increased and the expression level of p62 were decreased in both TG and celastrol treated cells, which indicated the significant activation of autophagy in spermatogonia cells. Therefore, autophagy plays an important role in the testicular injury induced by TG, and inhibition of autophagy is expected to reduce the testicular toxicity of TG.

Objective

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by significant difficulties in social interaction, communication, and repeated stereotypic behaviour. Aflatoxin B₁ (AFB₁) is the most potent and well-known mycotoxin in various food sources. Despite its propensity to generate significant biochemical and structural changes in human and animal tissues, the influence of AFB₁ on ASD has yet to be thoroughly studied. Mounting evidence indicates that chemokine receptors play a crucial function in the central nervous system and are implicated in developing several neuroinflammatory disorders. Chemokine receptors in individuals with ASD were elevated in the anterior cingulate gyrus astrocytes, cerebellum, and brain.

Methods

The BTBR T⁺Itpr3^tf/J (BTBR) mice are inbred strains that exhibit strong and consistently observed deficits in social interactions, characterized by excessive self-grooming and limited vocalization in social contexts. We examined the impact of AFB₁ on CCR3-, CCR7-, CCR9-, CXCR3-, CXCR4-, and CXCR6-expressing I-A/I-E⁺ cells in the spleen of the BTBR mouse model of autism. We evaluated the mRNA levels of CCR3, CCR7, CCR9, CXCR3, CXCR4, and CXCR6 chemokine receptors in the brain.

Results

The exposure to AFB₁ in BTBR mice resulted in a significant rise in the number of I-A/I-E⁺CCR3⁺, I-A/I-E⁺CCR7⁺, I-A/I-E⁺CCR9⁺, I-A/I-E⁺CXCR3⁺, I-A/I-E⁺CXCR4⁺, and I-A/I-E⁺CXCR6⁺ cells. Furthermore, exposure to AFB₁ increased mRNA expression levels of CCR3, CCR7, CCR9, CXCR3, CXCR4, and CXCR6 in the brain.

Conclusions

These findings highlight that AFB₁ exposure increases the expression of chemokine receptors in BTBR mice, indicating the necessity for further research into AFB₁'s role in the development of ASD.

Tributyltin (TBT), an organotin endocrine-disrupting substance, is recognized as one of the important toxic environmental pollutants. The present study was carried out to investigate the toxic effects of TBT on behavior and the ovary of adult zebrafish with a focus on oxidative stress markers and oocyte maturation. Adult zebrafish were exposed to three different concentrations (125, 250, and 500 ng/L of water) of TBT for 28 days. TBT exposure produced a concentration-dependent negative effect on the body weight and behavior (anxiety-like symptoms) of adult zebrafish. Alterations in the activity of superoxide dismutase (SOD) and catalase (CAT), the total antioxidant capacity of ovarian tissue by the highest exposure level of TBT resulted in lipid peroxidation as indicated by increased malondialdehyde (MDA) level. The numbers of early-vitellogenic oocytes were significantly increased in zebrafish exposed to TBT as low as 125 ng/L. However, the numbers and size of fully-grown (mature) oocytes were significantly reduced in the highest exposure group only. Correlation between the MDA level and pre-vitellogenic oocytes in the 500 ng/L group indicated that lipid peroxidation prevented the maturation of pre-vitellogenic oocytes. TBT exposure produced significant histological changes in the ovary as evidenced by disturbed maturation of oocytes. In conclusion, TBT adversely affected the maturation of oocytes in zebrafish ovary through oxidative stress-mediated mechanisms.

Tdap is an acronym for tetanus(T), diphtheria(D), and acellular pertussis(aP), and is a preventive vaccine that combines vaccines against three diseases. BVN008 is a Tdap vaccine designed to protect against three diseases: diphtheria, tetanus, and pertussis. The lower-case “d” and “p” in Td and Tdap means these vaccines use smaller amounts of diphtheria and whooping cough. The lower doses are appropriate for adolescents and adults. The purpose of this study was to identify adverse effects in pregnant or lactating female Sprague-Dawley rats including maternal fertility and toxicity, and development of the embryos, fetus, and pups following intramuscular administration of BVN008. Two groups of 50 female Sprague-Dawley rats were administered four or five intramuscular injections of the vaccine (human dose of 0.5 mL at 4 and 2 weeks before pairing, on gestation day (GD) 8 and 15, and lactation day (LD) 7. A negative control group was administered 0.9% saline at the same dose four or five times. There were no adverse effects on fertility, reproductive performance, or maternal toxicity of the F0 females. There was no effect of developmental toxicity in F1 fetuses and pups including fetal body weight and morphology, postnatal growth, development, and behavior until weaning. Antibodies against tetanus, diphtheria, and pertussis were transferred to the F1 fetuses and F1 pups via placenta and milk. These results demonstrate that BVN008 had no detectable adverse effects in either the F0 female rats, the F1 fetuses or pups.

The process of mammalian reproduction involves the development of fertile germ cells in the testis and ovary, supported by the surrounders. Fertilization leads to embryo development and ultimately the birth of offspring inheriting parental genome information. Any disruption in this process can result in disorders such as infertility and cancer. Chemical toxicity affecting the reproductive system and embryogenesis can impact birth rates, overall health, and fertility, highlighting the need for animal toxicity studies during drug development. However, the translation of animal data to human health remains challenging due to interspecies differences. In vitro culture systems offer a promising solution to bridge this gap, allowing the study of mammalian cells in an environment that mimics the physiology of the human body. Current advances on in vitro culture systems, such as organoids, enable the development of biomaterials that recapitulate the physiological state of reproductive organs. Application of these technologies to human gonadal cells would provide effective tools for drug screening and toxicity testing, and these models would be a powerful tool to study reproductive biology and pathology. This review focuses on the 2D/3D culture systems of human primary testicular and ovarian cells, highlighting the novel approaches for in vitro study of human reproductive toxicology, specifically in the context of testis and ovary.