BACKGROUND: Haematitum, a time-honored mineral-based Chinese medicine, has been used medicinally in China for over 2000 years. It is now included in the Chinese Pharmacopoeia and used clinically for treating digestive and respiratory diseases. The Chinese Materia Medica records that it is toxic and should not be taken for a long period, but there are few research reports on the toxicity of Haematitum and its potential toxicity mechanisms.
OBJECTIVE: This study aimed to evaluate the toxicity of Haematitum and calcined Haematitum, including organ toxicity, neurotoxicity, and reproductive toxicity. Further, it is also necessary to explore the mechanism of Haematitum toxicity and to provide a reference for the safe clinical use of the drug.
METHODS: The samples of Haematitum and calcined Haematitum decoctions were prepared. KM mice were treated with samples by gavage for 10 days, and lung damage and apoptosis were assessed by HE staining and TUNEL staining of lung tissues respectively. Metabolomics analysis was performed by HPLC-MS. Metallomics analysis was performed by ICP-MS. In addition, C. elegans was used as a model for 48 h exposure to examine the neurotoxicity and reproductive toxicity-related indices of Haematitum, including locomotor behaviors, growth and development, reproductive behaviors, AChE activities, sensory behaviors, apoptosis, and ROS levels.
RESULTS: The use of large doses of Haematitum decoction caused lung damage in mice. Neither calcined Haematitum decoction nor Haematitum decoction at clinically used doses showed organ damage. Metabolomics results showed that disorders in lipid metabolic pathways such as sphingolipid metabolism and glycerophospholipid metabolism may be important factors in Haematitum-induced pulmonary toxicity. High doses of Haematitum decoction caused neurological damage to C. elegans, while low doses of Haematitum decoction and calcined Haematitum decoction showed no significant neurotoxicity. Decoction of Haematitum and calcined Haematitum did not show reproductive toxicity to C. elegans. Toxicity was also not observed in the control group of iron (Ⅱ) and iron (Ⅲ) ions in equal amounts with high doses of Haematitum.
CONCLUSIONS: Haematitum is relatively safe for routine doses and short-term use. Calcination can significantly reduce Haematitum toxicity, and this study provides a reference for safe clinical use.

Reproductive disorders and declining fertility rates are significant public health concerns affecting birth rates and future populations. Male infertility, often due to spermatogenesis defects, may be linked to environmental pollutants like nickel nanoparticles (Ni NPs). Ni NPs are extensively utilized across different industries. Nevertheless, their potential adverse effects cannot be overlooked. Previous studies have linked the reproductive toxicity induced by Ni NPs with disturbances in mitochondrial function. Mitochondrial division/fusion dynamics are crucial to their proper function, yet little is known about how Ni NPs perturb these dynamics and whether such perturbation contributes to the impairment of the male reproductive system. Herein, we demonstrated that the exposure of Ni NPs to the mouse-derived spermatogonia cell line (GC-1 cells) triggered DRP1-mediated mitochondrial division and the enhanced impairment of mitochondria, consequently promoting mitochondria-dependent cell apoptosis. Notably, both the mitochondrial division inhibitor (Mdivi-1) and lentiviral-transfected cells with low expression of Dnm1l-DK in these cells could mitigate the toxic effects induced by Ni NPs, pointing to the potential role of mitochondrial dynamics in Ni NP-induced reproductive toxicity. Collectively, our work contributes to the understanding of the mechanisms by which Ni NPs can impact male reproductive function and identifies mitochondrial division as a potential target for intervention.

Platinum-based antitumor drugs are broad-spectrum agents with unique mechanisms of action. Combination chemotherapy regimens based on platinum drugs are commonly used in cancer treatment. However, these drugs can cause various adverse reactions in the human body through different routes of administration, including reproductive toxicity, genetic toxicity, and embryonic developmental toxicity. Preventing adverse effects is crucial to enhance patients\' quality of life and reduce healthcare costs. This article discusses the types and developmental history of antitumor active platinum compounds, their mechanisms of action, routes of administration, and their potential reproductive, genetic, and embryonic developmental toxicity. This text explores preventive measures based on animal experimental results. Its aim is to provide references for personalized treatment and occupational protection when using platinum drugs. The continuous progress of science and technology, along with the deepening of medical research, suggests that the application of platinum drugs will broaden. Therefore, the development of new platinum drugs will be an important direction for future research.

BACKGROUND: In this study, JJH201501 was examined for reproductive toxicity during the perinatal period to support its safety as a novel serotonergic agent (5-HT) antidepressant. Pregnant Sprague-Dawley rats (F0, n = 24/group) were continuously exposed to 0 (control), 6, 18, and 60 mg/kg body weight/day of JJH201501 by intragastric administration from gestation day 15 to lactation day 21.
METHODS: During this period, maternal toxicity was evaluated based on clinical signs, body weight, feed intake, delivery condition, litter parameters, and necropsy, with body weight, sex ratios, malformation incidence, physical, and neurodevelopmental assessments conducted on all offspring rats. Ten pups (male:female 1:1) from each dam within each dose group on postnatal day 4 (PND4) were randomly selected. One pair was evaluated for behavior evaluations (F1a) after PND35, one for reproduction performance (F1b) after 10 weeks, and three for organ weight and deformities (F1c) on PND35. After successful mating, F1b male rats were weighed and dissected to assess reproductive organ weight and sperm motility. Pregnant F1b rats were weighed and monitored for food intake twice weekly until laparotomy on GD14, which recorded live/dead fetuses, resorptions, implantations, corpora lutea, and uterine weight. Some statistical differences were found between the JJH-treated and control groups in maternal weight, food consumption, and F1 body weight and water maze performance.
RESULTS: Autopsy results showed that JJH201501 had a low cardiac index effect in F0, with no significant histopathological changes detected. Only one F1 offspring died in the high-dose group throughout the experiment. Due to the lack of dose-dependent effects and the consistent growth pattern of these alterations, the study findings do not suggest any toxicological significance for the observed results.
CONCLUSIONS: In conclusion, the no-observed-adverse-effect level of JJH201501 for perinatal rats is about 60 mg/kg b.w./day.

Objective: To investigate the reproductive toxicity of cadmium sulfide nanoparticles (Nano-CdS) with different particle sizes on male mice. Methods: In January 2019, 30 SPF grade male mice were randomly divided into a control group, an experimental group[CdS Ⅰ group (particle size approximately 5 nm), and a CdS Ⅱ group (particle size approximately 50 nm) ], with 10 mice in each group. The experimental group was orally gavaged with 100 mg/kg, once a day, while the control group was gavaged with an equal volume of physiological saline for 45 consecutive days. After 45 days, levels of cadmium accumulation in testis were determined directly by AAS, deformity and testicular histopathological changes were also observed. Serum testosterone levels were measured by enzyme-linked immunosorbentassay (ELISA), expression levels of P450scc, 17β-HSD and P450c17 mRNA were determined by real-time PCR. P450c17 protein was determinated by Western Blot. Results: The histopathological results showed that the testes of the experimental group mice showed varying degrees of damage; Ultrastructural observation showed that the ultrastructure of mouse testicular cells in each experimental group showed varying degrees of mitochondrial expansion and disappearance of cristae, as well as irregular nuclear membranes. The degree of damage in CdS Ⅰ group was milder than that in CdS Ⅱ group. Compared with the control group, the cadmium content in the testes of the CdS Ⅰ and CdS Ⅱ groups significantly increased (P=0.001, 0.001), and the CdS Ⅱ group was higher than the CdS Ⅰ group (P=0.001). Compared with the control group, the levels of testosterone in the CdS Ⅰ and CdS Ⅱ groups decreased with statistical significance (P=0.001, 0.001). Real time fluorescence quantitative PCR results showed that compared with the control group, the experimental group\'s P450scc, 17β-HSD. The expression levels of 17β-HSD and P450c17 mRNA were significantly reduced, with statistically significant differences (P=0.001, 0.001, 0.001), and CdS Ⅱ group 17β-HSD. The expression levels of 17β-HSD and P450c17 mRNA were significantly lower than those of CdS Ⅰ group (P=0.001, 0.036). The Western Blot assay results showed that the expression levels of P450c17 protein in the testes of CdS Ⅰ and CdS Ⅱ groups of mice were significantly reduced, with statistical significance (P=0.001, 0.001) ; And the CdS Ⅱ group was significantly lower than the CdS Ⅰ group (P=0.001). According to Spearman correlation analysis, testosterone levels are correlated with P450scc, P450c17, 17β-HSD mRNA. There is a highly positive correlation between 17β-HSD mRNA levels, with statistically significant differences (r(s)=0.88, 0.80, 0.70, P=0.001, 0.001, 0.004) . Conclusion: Nano cadmium sulfide may induce reproductive toxicity by reducing the expression levels of key enzyme genes and enzyme protein activity in testosterone and its synthesis in mice, and the CdS Ⅱ group has a stronger toxic effect.
目的： 探讨不同粒径的纳米硫化镉（Nano-CdS）对雄性小鼠的生殖毒性。 方法： 于2019年1月，将30只SPF级雄性小鼠随机分为对照组、实验组[CdS I组（粒径约5 nm）和CdS Ⅱ组（粒径约50 nm）]，每组10只。实验组经口灌胃100 mg/kg Nano-CdS，1次/d，对照组灌胃等体积生理盐水，连续45 d。观察小鼠睾丸组织的病理学变化，使用透射显微镜观察睾丸组织中细胞核、线粒体等细胞器的超微结构，采用石墨炉原子吸收光谱法（AAS）检测睾丸组织中镉元素富集水平，采用ELISA试剂盒测定血清中睾酮激素水平，采用实时荧光定量PCR检测睾丸组织中基因细胞色素P450胆固醇侧链裂解酶（P450scc）、17α-羟化酶（P450c17）、17β羟基类固醇脱氢酶（17β-HSD）mRNA表达水平。采用Western Blot测定P450c17蛋白的表达水平。 结果： 组织病理学结果显示实验组小鼠睾丸均出现不同程度损伤；超微结构观察显示各实验组的小鼠睾丸细胞的超微结构均不同程度线粒体膨胀和嵴消失，核膜的不规则，CdS Ⅰ组损伤程度轻于CdSⅡ组。与对照组比较，CdS Ⅰ组和CdS Ⅱ组小鼠血清睾丸镉元素含量明显增加（P=0.001、0.001），CdSⅡ组高于CdSⅠ组（P=0.001）。与对照组比较，CdS Ⅰ组和CdSⅡ组小鼠血清睾酮水平降低，差异有统计学意义（P=0.001、0.001）。实时荧光定量PCR结果显示：与对照组比较，实验组的P450scc、P450c17 mRNA表达水平明显降低，差异有统计学意义（均P<0.05），CdSⅡ组17β-HSD mRNA表达水平降低（P=0.001）；且CdSⅡ组17β-HSD、P450c17 mRNA表达水平明显低于CdSⅠ组（P=0.001、0.036）。Western Blot测定结果显示：CdSⅠ组和CdSⅡ组小鼠睾丸中P450c17蛋白表达水平明显降低，差异有统计学意义（P=0.001、0.001）；且CdS Ⅱ组明显低于CdS Ⅰ组（P=0.001）。经Spearman相关分析，睾酮水平与P450scc、P450c17、17β-HSD mRNA水平之间呈正相关，差异有统计学意义（r(s)=0.88、0.80、0.70，P=0.001、0.001、0.004）。 结论： 纳米硫化镉可能通过降低小鼠的睾酮及其合成关键酶基因表达水平及酶蛋白活性从而产生生殖毒性，且CdS Ⅱ组毒性作用更强。.

Continuous dopaminergic stimulation (CDS) has become an important strategy for the development of drugs to treat Parkinson\'s disease (PD). Rotigotine behenate extended-release microspheres (RBEM) for injection represent a new treatment regime for CDS and are undergoing clinical trials. In this study, we aimed to investigate the effect of RBEM on genotoxicity, fertility and early embryonic development. We used the Ames test, Chinese hamster lung (CHL) cell chromosome aberration test and the mouse bone marrow micronucleus test, to evaluate the genotoxicity of RBEM. These tests were all negative, thus indicating that RBEM did not induce genotoxicity. In reproduction toxicity testing in male rats on obvious findings following intramuscular administration (i.m.) of RBEM at up to 540 mg/kg (P > 0.5), when female rats were administered with RBEM in the dose range of 60 to 540 mg/kg given (i.m.), there were clear effects on fertility and early embryonic development. These results indicated that RBEM could induce toxicity in female rats and exert effect on fertility and early embryonic development stage.

The reproductive toxicity of polycyclic aromatic hydrocarbons (PAHs) in aquatic organisms has attracted increasing attention from scholars. Currently, research in this field primarily focuses on vertebrates such as zebrafish and other model species. However, there is still a significant knowledge gap in the toxicity of PAHs to invertebrates and its potential mechanisms. Benzo[a]pyrene (B[a]P) is one of the most representative PAHs. In this study, female Ruditapes philippinarum (R. philippinarum) was treated with B[a]P concentrations of 0, 0.8, 4, and 20 μg/L to investigate reproductive indicators in the proliferative, growth, mature, and spawn stages. Transcriptomics was used to investigate the expression of genes associated with the reproductive endocrine system, DNA repair, autophagy, apoptosis, and ovarian development at different reproductive stages. Our results suggested that B[a]P disrupted the endocrine system by interfering with the production of steroid hormones and the transmission of estrogen signals in female R. philippinarum. The structure of the ovarian DNA duplex is severely damaged under the stress of B[a]P, and a series of cellular responses caused by DNA damage are also interfered. Additionally, we observed a reduction in the gonadosomatic index (GSI) and mature oocytes numbers after B[a]P exposed. Tissue section indicated that severe damage to the ovarian structure at mature and spawn stages. In conclusion, this study combined transcriptomic and toxicological to explore the negative effects on ovarian development induced by B[a]P, focusing on reproductive endocrine disturbance and DNA damage.

Few studies were found for neurobehavioral toxicity of dinotefuran in mammals. This study was designed to evaluate the reproductive and neurobehavioral effects of dinotefuran exposure in mice.
Dinotefuran was given in the diet to provide levels of 0% (control), 0.015%, 0.03%, and 0.06% from 5 weeks of age of the F0 generation to 11 weeks of age of the F1 generation in mice. Selected reproductive and neurobehavioral parameters were measured.
Movement time increased with a significant dose-related trend, and the related variables of rearing time decreased in significant dose-related trends in adult males in the F0 generation. Litter size and weight increased in significant dose-related trends, and sex ratio decreased in a significant dose-related trend. The average body weight of offspring increased in a significant dose-related trend on postnatal day (PND) 21 in both sexes. In the olfactory orientation on PND 14 in female offspring, the time required lengthened in a significant dose-related trend. In male offspring, total distance and the average speed decreased in significant dose-related trends, and the average time of rearing, number of defecations, and frequencies of mice with urination increased in a significant dose-related trend. In female offspring, the related variables of rearing increased in significant dose-related trends. In spontaneous behavior of males, the parallel lines during the control and treatment groups indicated a significant distance in the number of horizontal activities.
The dose levels of dinotefuran in the present study produced several adverse effects on reproductive and neurobehavioral parameters in mice.

UNASSIGNED: It has been reported that some herbal products affect reproduction. To date, reproductive toxicity of Syzygium guineense has not been investigated although the plant is widely used in treating fertility related problems. Thus, the objective of the current study was to investigate the toxic effects of 70% ethanol extract of S. guineense leaves on the reproductive function and histopathology of reproductive organs in female rats.
UNASSIGNED: Eighty female Wistar albino rats were randomly divided into four groups where each group consisted of 20 rats. Rats in the first three groups were treated with S. guineense extract at doses of 250, 500 and 1000 mg/kg body weight, respectively. The fourth group served as a control group. The rats were treated for ten consecutive weeks. The length of estrous cycle, reproductive indices, pregnancy outcomes, and number of postnatal deaths were recorded. At necropsy, organ weight was measured, gross and histopathological examinations of ovaries, uterus, and vagina were conducted.
UNASSIGNED: Treatment of rats, with high dose (1000 mg/kg) of S. guineense, significantly prolonged the duration of estrous cycle and reduced weight of uterus and ovaries as well as the number of total and live birth pups. However, there were no significant changes observed in reproductive indices and gross morphology as well as histopathology of ovaries, uterus, and vagina.
UNASSIGNED: Administration of high doses of S. guineense could be toxic to some aspects of the reproductive system of female rats and might also affect reproduction. Therefore, consuming high dose of S. guineense leaves is not recommended.

The field of Paternal Origins of Health and Disease (POHaD) is highly relevant but remains under-explored. The F2 generation from males indirectly exposed (F1 - via germ cells) to benzo(a)pyrene (BaP), named PF2, was investigated in this study under parameters of sexual development and reproductive performance of male and female rats. Male Wistar rats (F0) were exposed to BaP (0.1 µg/kg/day) for 31 consecutive days (gavage) during prepuberty. The F0 rats were mated with untreated females to produce male offspring (F1), which were exposed to BaP via germ cells. The F1 males were later mated with untreated females to obtain the PF2 generation, which was the focus of our investigation. Our findings showed that PF2 males exhibited a decrease in anogenital distance, fertility potential, testosterone levels, and type A sperm. Meanwhile, PF2 females had an earlier vaginal opening, lower lordosis scores, and decreased fertility. Furthermore, changes in the histomorphology of the testis/epididymis and ovary/uterus were observed. The repercussions of the PF2 generation indicate that these animals showed losses in both sexual development and fertility potential, and we can conclude that this damage remained due to paternal transgenerational inheritance caused by a low dose of BaP.