Reproductive and developmental safety evaluation of Thymelaea hirsuta (L.) leaves aqueous extract in Wistar albino rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The popularity of herbal medicine is expanding globally due to the common belief that herbal products are natural and nontoxic. Thymelaea hirsuta leaves are traditionally used for the treatment of recurrent abortion in humans and animals. However, a lack of safety evaluation of the plant, particularly in pregnant women, raises serious concerns regarding its potential embryotoxic effects. AIM OF THE STUDY: Therefore, the present study investigated the safety of Thymelaea hirsuta leaves aqueous extract (THLE) during pregnancy and lactation following maternal rat treatment. MATERIALS AND METHODS: THLE phytochemical compounds were identified using high-performance liquid chromatography (HPLC). THLE was orally administered to pregnant rats and lactating dams at dosages of 0, 250, 500, and 1000 mg/kg/day. At the end of the study, dam s' and pups' body weights, serum biochemical and hematological indices, and histopathological changes were investigated. For the fetal observation and histopathological changes were also evaluated. RESULTS: Our findings revealed that THLE is rich in different phenolic and flavonoid compounds. However, biochemical and hormonal parameters such as ALT, AST, and prolactin were significantly increased in dams treated with a higher dosage of THLE when compared to the control dams (P ≤ 0.05). Additionally, external, visceral and skeletal examinations of fetuses revealed a marked increase of malformation rates in treated fetuses. CONCLUSIONS: The results revealed that higher oral dosing of THLE during pregnancy could affect embryonic development in rats, while lower doses are safe and can be used during pregnancy and lactation to attain its beneficial effects.

4-Nitrophenol at environmentally relevant concentrations mediates reproductive toxicity in Caenorhabditis elegans via metabolic disorders-induced estrogen signaling pathway.

4-Nitrophenol (4-NP), as a toxic and refractory pollutant, has generated significant concern due to its adverse effects. However, the potential toxic effects and mechanism remained unclear. In this study, the reproduction, development, locomotion and reactive oxygen species (ROS) production of Caenorhabditis elegans were investigated to evaluate the 4-NP toxicity. We used metabolomics to assess the potential damage mechanisms. The role of metabolites in mediating the relationship between 4-NP and phenotypes was examined by correlation and mediation analysis. 4-NP (8 ng/L and 8 µg/L) caused significant reduction of brood size, ovulation rate, total germ cells numbers, head thrashes and body bends, and an increase in ROS. However, the oosperm numbers in uterus, body length and body width were decreased in 8 µg/L. Moreover, 36 differential metabolites were enriched in the significant metabolic pathways, including lysine biosynthesis, ß-alanine metabolism, tryptophan metabolism, pentose phosphate pathway, pentose and glucuronate interconversions, amino sugar and nucleotide sugar metabolism, starch and sucrose metabolism, galactose metabolism, propanoate metabolism, glycerolipid metabolism, and estrogen signaling pathway. The mechanism of 4-NP toxicity was that oxidative stress caused by the perturbation of amino acid, which had effects on energy metabolism through disturbing carbohydrate and lipid metabolism, and finally affected the estrogen signaling pathway to exert toxic effects. Moreover, correlation and mediation analysis showed glycerol-3P, glucosamine-6P, glucosamine-1P, UDP-galactose, L-aspartic acid, and uracil were potential markers for the reproduction and glucose-1,6P2 for developmental toxicity. The results provided insight into the pathways involved in the toxic effects caused by 4-NP and developed potential biomarkers to evaluate 4-NP toxicity.

Lifetime trajectories of male mating effort under reproductive conflict in a cooperatively breeding mammal.

The costs of reproductive conflict can shape the evolution of life-histories in animal societies. These costs may change as individuals age and grow, and with within-group competition. Social costs of reproductive conflict have been invoked to explain why females might gain from delaying maturity or ceasing reproduction midway through life, but not in males. Here, we analyse more than 20 years of data to understand how individual male banded mongooses adjust their reproductive activity in response to the costs of reproductive conflict. In banded mongoose groups, multiple female breeders enter oestrus synchronously that are each guarded by a single male that aggressively wards-off rivals. The heaviest males in the group gained the greatest share of paternity. Those lighter males that are reproductively active paid disproportionate survival costs, and by engaging in reproductive activity early had lower lifetime reproductive success. Our results suggest that reproductive inactivity early in life is adaptive, as males recoup any lost fitness by first growing before engaging in less costly and more profitable reproductive activity later in life. These results suggest that resource holding potential of males and the intensity of reproductive conflict interact to shape lifetime schedules of reproductive behaviour.

Addictive manipulation: a perspective on the role of reproductive parasitism in the evolution of bacteria-eukaryote symbioses.

Wolbachia bacteria encompass noteworthy reproductive manipulators of their arthropod hosts. which influence host reproduction to favour their own transmission, also exploiting toxin-antitoxin systems. Recently, multiple other bacterial symbionts of arthropods have been shown to display comparable manipulative capabilities. Here, we wonder whether such phenomena are truly restricted to arthropod hosts. We focused on protists, primary models for evolutionary investigations on eukaryotes due to their diversity and antiquity, but still overall under-investigated. After a thorough re-examination of the literature on bacterial-protist interactions with this question in mind, we conclude that such bacterial 'addictive manipulators' of protists do exist, are probably widespread, and have been overlooked until now as a consequence of the fact that investigations are commonly host-centred, thus ineffective to detect such behaviour. Additionally, we posit that toxin-antitoxin systems are crucial in these phenomena of addictive manipulation of protists, as a result of recurrent evolutionary repurposing. This indicates intriguing functional analogy and molecular homology with plasmid-bacterial interplays. Finally, we remark that multiple addictive manipulators are affiliated with specific bacterial lineages with ancient associations with diverse eukaryotes. This suggests a possible role of addictive manipulation of protists in paving the way to the evolution of bacteria associated with multicellular organisms.

Paternity success for resident and non-resident males and their influences on paternal sibling cohorts in Japanese macaques (Macaca fuscata) on Shodoshima Island.

Reproductive success can be attributed to both resident and non-resident males in non-human primates. However, reproductive success of non-resident males has rarely been investigated at an individual level. As resident males achieve different degree of reproductive success with regard to various factors, such as male dominance relationships or female mate choice, the degree of reproductive success for non-resident males may vary between individuals. As male reproductive success is highly skewed towards specific individuals, the percentage of similar-aged paternal siblings within groups is expected to increase. However, the extent to which each male contributes to the production of cohorts of paternal siblings remains unclear. Here we examined the paternity of offspring born over five consecutive years in a free-ranging group of Japanese macaques Macaca fuscata on Shodoshima Island, Kagawa Prefecture. Genotypes of 87 individuals at 16 autosomal microsatellite loci were analyzed and paternity of 34 offspring was successfully assigned to a single candidate father. We quantitatively assessed paternity success for resident and a few non-resident males whose genetic samples were successfully collected. We quantitatively assessed the percentages of paternal siblings in the same age cohorts produced by those males. Non-resident males sired similar percentage of offspring compared to resident males. A large prime-aged non-resident male was the most successful sire among males in two of the five years. These results provide new insights that male reproductive success could be highly skewed toward a specific non-resident male. Subadult males had a lower percentage of paternity success, which may be because females may prefer physically mature males. Various males, including non-resident males, contributed to the creation of paternal sibling in the same age cohort. The overall results highlighted that not only resident but also non-resident males play an important role in shaping within-group kin structures.

Isolation limits spring pollination in a UK fragmented landscape.

Animal-mediated pollination determines the reproductive success of most flowering plants; this process however can be disrupted by environmental degradation, with habitat loss and fragmentation highlighted as a top driver of pollination deficits. Despite being a pervasive stressor worldwide, we still have rather limited empirical evidence on its effects on pollination services, especially for early spring pollination syndromes. We investigate this using a potted plant phytometry experiment in which we placed English Bluebell (Hyacinthoides non-scripta)-a species largely pollinated in spring-into a fragmented woodland habitat. We selected 51 woodland patches which varied in both size and distance from each other and placed 153 pots of bluebell plants in the patches for c.4 weeks to measure pollination. The woodlands were located in a matrix of grassland, the latter being of low plant species richness and overall in the patches, woodland plants showed a positive species-area relationship. We collected traits on bluebell reproduction, these included the number, size, quality of seeds, the number of seed capsules and the number of flowers that failed to set any seeds. We found that seed traits responded differently to patch area and isolation. Patch isolation negatively affected the number of seeds and capsules, whilst it did not affect the size and quality of seeds. Patch area had no effect on any traits, suggesting that patch area might not necessarily be a factor that affects pollination in this species. The number of flowers that failed to set seed was unaffected by either patch area or isolation. Our study suggests that woodland fragmentation impacts the pollination of understory spring flowering plants. Our results highlight the use of multiple traits of phytometer plants to evaluate pollination and the importance of connectivity in maintaining pollination services in small-fragmented landscapes.

Genetic and genomic analysis of reproduction traits in holstein cattle using SNP chip data and imputed sequence level genotypes.

BACKGROUND: Reproductive performance plays an important role in animal welfare, health and profitability in animal husbandry and breeding. It is well established that there is a negative correlation between performance and reproduction in dairy cattle. This relationship is being increasingly considered in breeding programs. By elucidating the genetic architecture of underlying reproduction traits, it will be possible to make a more detailed contribution to this. Our study followed two approaches to elucidate this area; in a first part, variance components were estimated for 14 different calving and fertility traits, and then genome-wide association studies were performed for 13 reproduction traits on imputed sequence-level genotypes with subsequent enrichment analyses. RESULTS: Variance components analyses showed a low to moderate heritability (h2) for the traits analysed, ranging from 0.014 for endometritis up to 0.271 for stillbirth, indicating variable degrees of variation within the reproduction traits. For genome-wide association studies, we were able to detect genome-wide significant association signals for nine out of 13 analysed traits after Bonferroni correction on chromosome 6, 18 and the X chromosome. In total, we detected over 2700 associated SNPs encircling more than 90 different genes using the imputed whole-genome sequence data. Functional associations were reviewed so far known and potential candidate regions in the proximity of reproduction events were hypothesised. CONCLUSION: Our results confirm previous findings of other authors in a comprehensive cohort including 13 different traits at the same time. Additionally, we identified new candidate genes involved in dairy cattle reproduction and made initial suggestions regarding their potential impact, with special regard to the X chromosome as a putative information source for further research. This work can make a contribution to reveal the genetic architecture of reproduction traits in context of trait specific interactions.

Identification and analysis of JHBP/TO family genes and their roles in the reproductive fitness cost of resistance in Frankliniella occidentalis (Pergande).

The juvenile hormone binding protein (JHBP) and takeout (TO) genes, mediated by the juvenile hormone (JH), play a crucial role in regulating the reproductive physiology of insects. Our previous study revealed that spinosad-resistant Frankliniella occidentalis (NIL-R) exhibited reduced fecundity and significant changes in JHBP/TO family gene expression. We hypothesized that these genes were involved in regulating the fitness costs associated with resistance. In this study, 45 JHBP/TO genes were identified in F. occidentalis, among which FoTO2 and FoTO10 were duplicates. Additionally, eight genes exhibited significant down-regulation in the NIL-R population. Two genes (FoTO6 and FoTO24) that exhibited the most significant differential expression between the spinosad-susceptible (Ivf03) and NIL-R populations were selected to investigate their roles in resistance fitness using RNA interference (RNAi). Following interference with FoTO6, FoTO24, and their combination, the expression levels of vitellogenin (Vg) were downregulated by 3%-30%, 13%-28%, and 14%-32% from the 2nd day to the 5th day, respectively; Krüppel-homolog 1 (Kr-h1) expression was down-regulated by 3%-65%, 11%-34%, and 11%-39% from the 2nd day to the 5th day, respectively; ovariole length was shortened by approximately 18%, 21%, and 24%, respectively; and the average number of eggs decreased from 407 to 260, 148, and 106, respectively. Additionally, a JH supplementation experiment on the NIL-R population revealed that the expression levels of both FoTO6, FoTO24, Vg and Kr-h1 were significantly upregulated compared with those observed in the Ivf03 population, resulting in increased fecundity. These results suggest that FoTO6 and FoTO24 are involved in JH-mediated regulation of the reproductive fitness cost of resistance to spinosad. Further, FoTO6 and FoTO24 can be considered potential target genes for applying RNAi technology in the scientific management of F. occidentalis.

Application of a new approach method to assess the hazard of complex legacy contaminated groundwater mixtures on fathead minnows in outdoor mesocosms.

Assessing the environmental risks of contaminated groundwater presents significant challenges due to its often-complex chemical composition and to dynamic processes affecting exposure of organisms in receiving surface waters. The objective of this study was to characterize the effects of groundwater collected from a legacy contaminated industrial site, in fish under environmentally relevant conditions. A 21-day fish short-term reproduction assay was conducted in outdoor wetland mesocosms by exposing adult fathead minnows (Pimephales promelas) to graded concentrations of groundwater (1 %, 3 %, and 6 %). Offspring were held in mesocosms up to four days post-hatch to apply a new approach method (NAM), the EcoToxChip™, to explore whether traditional apical endpoints could be predicted using an alternative mechanistic approach. None of the groundwater concentrations used in this study were lethal to fish. There was greater cumulative number of eggs produced at the highest concentration of exposure. However, no abnormal histological appearance was observed in the liver and gonads of fish and no significant effect was observed in the relative expression of genes, tubercle counts, and erythrocyte micronuclei counts compared to the negative control. Food availability in the mesocosms was also assessed and the abundance of zooplankton increased in all groundwater-treated mesocosms. Fathead minnow findings are in contrast to those obtained from previous controlled laboratory studies that revealed significant genotoxicity, hepatotoxicity, and reprotoxicity of the same mixtures. Several factors could explain these observations, including the aging of groundwater in mesocosms before fish addition resulting in photo- and biodegradation and binding to sediments of toxic components. Our static exposure scenario likely underestimated realistic exposure scenarios where groundwater inflow to surface water is generally semi-continuous. Nevertheless, focused transcriptome analysis using EcoToxChips also observed greater toxicity during previous laboratory tests compared to mesocosm scenarios, and thus, our results support the use of this NAM in the ecological risk assessment of contaminated groundwater.

Antioxidants in mitigating phthalate-induced male reproductive toxicity: A comprehensive review.

Phthalates, widely used as plasticizers, have been increasingly linked to male reproductive toxicity through mechanisms including oxidative stress, endocrine disruption, inflammation, and apoptosis. This comprehensive review evaluates the protective role of various antioxidants in mitigating the detrimental effects of phthalates such as di-(2-ethylhexyl) phthalate (DEHP), di-butyl phthalate (DBP), mono-(2-ethylhexyl) phthalate (MEHP), and monobutyl phthalate (MBP) on male reproductive health. Antioxidants such as lycopene, ellagic acid, genistein, and selenium compounds exhibit significant efficacy in counteracting phthalate-induced damage by neutralizing reactive oxygen species (ROS), enhancing endogenous antioxidant defenses, reducing inflammatory responses, and preventing apoptosis. Lycopene demonstrates broad-spectrum protective effects, particularly through its high ROS-scavenging capacity and ability to preserve mitochondrial function. Ellagic acid effectively ameliorates oxidative stress and inflammation, while genistein enhances the Nrf2 pathway and restores hormonal balance, offering robust protection against reproductive toxicity. Selenium compounds improve antioxidant enzyme activities, providing essential support against oxidative damage. These findings underscore the potential of antioxidants as therapeutic agents against phthalate-induced male reproductive dysfunction. Future research should focus on optimizing antioxidant combinations, understanding dose-response relationships, and assessing long-term efficacy and safety to develop effective interventions for safeguarding male reproductive health.

Adolescent exposure to tris(1,3-dichloro-2-propyl) phosphate (TCPP) induces reproductive toxicity in zebrafish through hypothalamic-pituitary-gonadal axis disruption.

Tris(1,3-dichloro-2-propyl) phosphate (TCPP), a prevalent organophosphorus flame retardant in aquatic environments, has raised significant concerns regarding its ecological risks. This study aims to explore the impacts of TCPP on the reproductive functions of zebrafish and delineate its gender-related toxic mechanisms. By assessing the effects on zebrafish of 10 mg/L TCPP exposure from 30 to 120 days post-fertilization (dpf), we thoroughly evaluated the reproductive capability and endocrine system alterations. Our findings indicated that TCPP exposure disrupted gender differentiation in zebrafish and markedly impaired their reproductive capacity, resulting in decreased egg laying and offspring development quality. Histological analyses of gonadal tissues showed an abnormal increase in immature oocytes in females and a reduction in mature sperm count and spermatogonial structure integrity in males, collectively leading to compromised embryo quality. Additionally, molecular docking results indicated that TCPP showed a strong affinity for estrogen receptors, and TCPP-treated zebrafish exhibited imbalanced sex hormones and increased estrogen receptor expression. Alterations in genes associated with the hypothalamic-pituitary-gonadal (HPG) axis and activation of the steroidogenesis pathway suggested that TCPP targets the HPG axis to regulate sex hormone homeostasis. Tamoxifen (TAM), as a competitive inhibitor of estrogen, exhibited a biphasic effect, as evidenced by the counteraction of TCPP-induced effects in both male and female zebrafish after TAM addition. Overall, our study underscored the gender-dependent reproductive toxicity of TCPP exposure in zebrafish, characterized by diminished reproductive capacity and hormonal disturbances, likely due to interference in the HPG axis and steroidogenesis pathways. These findings emphasize the critical need to consider gender differences in chemical risk assessments for ecosystems and highlight the importance of understanding the mechanisms underlying the effects of chemical pollutants on the reproductive health of aquatic species.

Succession of rumen microbiota and metabolites across different reproductive periods in different sheep breeds and their impact on the growth and development of offspring lambs.

BACKGROUND: The microbiota and metabolites in the gastrointestinal tracts of female animals at different reproductive periods are very important to the growth, development, and health of themselves and their offspring. However, the changes in the gastrointestinal microbiota and metabolites throughout reproductive period of different sheep breeds and their effects on the growth and development of offspring lambs are still unclear. Hence, this study presents an assessment of the reproductive hormone levels, immune levels, rumen microbiota, and metabolites in Hu sheep and Suffolk ewes at different reproductive periods and their effects on the growth and development of offspring lambs. RESULTS: Hu sheep and Suffolk during non-pregnancy, pregnancy, and lactation were used as the research objects to determine reproductive and immune indexes of ewes at different periods, analyze rumen microbiome and metabolome, and track the growth performance and development of offspring lambs. The results showed that the reproductive hormone and immune levels of Hu sheep and Suffolk underwent adaptive changes across different reproductive periods. Compared with non-pregnancy, the microbial energy metabolism and lipid metabolism function decreased during Hu sheep pregnancy, and energy metabolism function decreased during lactation. In Suffolk, energy metabolism, glycan biosynthesis, and metabolism function were enhanced during pregnancy, and the metabolism of cofactors and vitamins was enhanced during lactation. Prevotella increased in Suffolk during pregnancy and lactation (P < 0.05) and was positively correlated with the birth weight and body size of the lambs (P < 0.05). Moreover, the abundances of Butyrivibrio and Rikenellaceae_RC9_gut_group during pregnancy were positively correlated with the intestinal immunity of the offspring lambs (P < 0.05), thereby regulating the intestinal immunity level of the lambs. Metabolomic analysis revealed that the protein digestion, absorption, and amino acid metabolism of Hu sheep were enhanced during pregnancy, which provided amino acids for the growth and development of pregnant ewes and fetuses and was significantly correlated with the birth weight, body size, and intestinal immunity of lambs (P < 0.05). Simultaneously, there was an increase in acetate and propionate during the pregnancy and lactation period of both Hu sheep and Suffolk, providing energy for ewes during reproductive period. Moreover, the microbiota during the lactation period was significantly correlated with the milk quality and lambs daily gain (P < 0.05). CONCLUSIONS: This study revealed the characteristic succession changes in the rumen microbiota and its metabolites at different reproductive periods in sheep breeds and their regulation of reproductive hormone and immune levels and identified their potential effects on the growth and development of offspring lambs. The findings provide valuable insights into the health and feeding management of different sheep breeds during the reproductive stage. Video Abstract.

Impact of the novel chlorinated polyfluorinated ether sulfonate, F-53B, on gill structure and reproductive toxicity in zebrafish.

6:2 Chlorinated polyfluorinated ether sulfonate, commonly known as F-53B, is widely used as a mist suppressant in various industries and is frequently detected in the environment. Despite its prevalent presence, the adverse effects of F-53B are not well understood and require future investigation. This study utilized zebrafish embryos and adults to examine the toxic effects of F-53B. Our findings revealed that F-53B impaired gill structure and increased erythrocyte numbers in adult zebrafish. Notably, F-53B demonstrated a higher sensitivity for inducing mortality (LC50 at 96 h) in adult zebrafish compared to embryos. Additionally, F-53B disrupted the expression of critical steroidogenic genes and hindered sex hormone production, which negatively affecting egg production. In conclusion, this study underscores the detrimental impact of F-53B on gill structure and reproductive toxicity in zebrafish, providing valuable insights into its overall toxicity.

The Impact of the Endocrine and Immunological Function of Adipose Tissue on Reproduction in Women with Obesity.

Obesity, which leads to metabolic dysregulation and body function impairment, emerges as one of the pressing health challenges worldwide. Excessive body fat deposits comprise a dynamic and biologically active organ possessing its own endocrine function. One of the mechanisms underlying the pathophysiology of obesity is low-grade systemic inflammation mediated by pro-inflammatory factors such as free fatty acids, lipopolysaccharides, adipokines (including leptin, resistin and visfatin) and cytokines (TNF-α, IL-1ß, Il-6), which are secreted by adipose tissue. Together with obesity-induced insulin resistance and hyperandrogenism, the exacerbated immune response has a negative impact on the hypothalamic-pituitary-gonadal axis at all levels and directly affects reproduction. In women, it results in disrupted ovarian function, irregular menstrual cycles and anovulation, contributing to infertility. This review focuses on the abnormal intracellular communication, altered gene expression and signaling pathways activated in obesity, underscoring its multifactorial character and consequences at a molecular level. Extensive presentation of the complex interplay between adipokines, cytokines, immune cells and neurons may serve as a foundation for future studies in search of potential sites for more targeted treatment of reproductive disorders related to obesity.

The Role of Selected Elements in Oxidative Stress Protection: Key to Healthy Fertility and Reproduction.

Oxidative stress and its relationship to fertility and reproduction is a topic of interest in medicine, especially in the context of the effects of trace elements and micronutrients. Oxidative stress occurs when there is an excess of free radicals in the body, which can lead to cell and tissue damage. Free radicals are reactive oxygen species (ROS) that can be formed as a result of normal metabolic processes, as well as under the influence of external factors such as environmental pollution, UV radiation, and diet. Oxidative stress has a significant impact on fertility. In men, it can lead to DNA damage in sperm, which can result in reduced semen quality, reduced sperm motility and increased numbers of defective sperm, and free radical damage to sperm cell membranes causing a reduction in the number of available sperm. In women, oxidative stress can affect the quality of female reproductive cells, which can lead to problems with their maturation and with embryo implantation in the uterus and can also affect ovarian function and disrupt hormonal regulation of the menstrual cycle. A proper balance of trace elements and micronutrients is key to protecting against oxidative stress and maintaining reproductive health. Supplementation with appropriate elements such as zinc, selenium, copper, manganese, chromium, and iron can help reduce oxidative stress and improve fertility. This work discusses the effects of selected elements on oxidative stress parameters specifically in terms of fertility and reproduction.

Identification and Functional Exploration of BraGASA Genes Reveal Their Potential Roles in Drought Stress Tolerance and Sexual Reproduction in Brassica rapa L. ssp. pekinensis.

Gibberellic acid-stimulated Arabidopsis sequences (GASAs) are a subset of the gibberellin (GA)-regulated gene family and play crucial roles in various physiological processes. However, the GASA genes in Brassica rapa have not yet been documented. In this study, we identified and characterized 16 GASA genes in Chinese cabbage (Brassica rapa L. ssp. pekinensis). Analysis of the conserved motifs revealed significant conservation within the activation segment of BraGASA genes. This gene family contains numerous promoter elements associated with abiotic stress tolerance, including those for abscisic acid (ABA) and methyl jasmonate (MeJA). Expression profiling revealed the presence of these genes in various tissues, including roots, stems, leaves, flowers, siliques, and callus tissues. When plants were exposed to drought stress, the expression of BraGASA3 decreased notably in drought-sensitive genotypes compared to their wild-type counterparts, highlighting the potentially crucial role of BraGASA3 in drought stress. Additionally, BraGASAs exhibited various functions in sexual reproduction dynamics. The findings contribute to the understanding of the function of BraGASAs and provide valuable insights for further exploration of the GASA gene function of the BraGASA gene in Chinese cabbage.