Premature ovarian insufficiency (POI) is a reproductive disorder characterized by impaired ovarian function. Cisplatin, a chemotherapeutic agent, is an important cause of acquired POI due to its ovarian toxicity, yet effective therapeutic interventions remain limited. Platelet-rich plasma (PRP) has gained increasing attention in regenerative medicine for its potential in tissue repair. This study investigated whether PRP could mitigate cisplatin-induced POI in rats and explored the underlying mechanisms. Female rats were randomly divided into control, cisplatin-induced POI, and CP + PRP groups. Ovarian function was assessed by serum hormone levels, estrous-stage patterns, ovarian morphology, ovarian index, and follicle counting. Oxidative stress levels and antioxidant capacity were assessed by measuring the levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px). Granulosa cell apoptosis was examined through immunohistochemistry for apoptosis-related proteins and TUNEL staining. PRP treatment partially improved ovarian function in cisplatin-induced POI rats, as evidenced by increased ovarian index, improved serum hormone profiles, more organized estrous-stage patterns, and preservation of follicular development. PRP also alleviated ovarian oxidative stress, as evidenced by reduced ROS and MDA levels and improved antioxidant capacity. Furthermore, PRP inhibited granulosa cell apoptosis, as demonstrated by decreased Bcl-2-associated X protein (Bax) expression, increased B-cell lymphoma 2 (Bcl-2) expression, and a reduced number of TUNEL-positive cells. These findings suggest that PRP may ameliorate cisplatin-induced POI in rats by alleviating oxidative stress and inhibiting apoptosis, providing experimental evidence for PRP as a potential therapeutic approach for chemotherapy-induced ovarian injury.

The present study aimed to investigate the potential protective effect of rivastigmine (RIVA) against doxorubicin (DOX)-induced ovarian injury in female rats, with particular emphasis on its anti-inflammatory, antioxidant, and antiapoptotic effects. Thirty-two adult female albino rats were randomly divided into four groups: control, RIVA (0.3 mg/kg, intraperitoneally), DOX (10 mg/kg, intraperitoneally), and RIVA + DOX groups. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Müllerian hormone (AMH) levels, as well as Alpha-7 Nicotinic Acetylcholine Receptor (α7nAChR) gene expression, were assessed. Ovarian oxidative stress, inflammatory, and apoptotic biomarkers were also evaluated. Histopathological examination of the ovaries and immunohistochemical assessment of caspase-3 expression were performed. DOX significantly increased serum FSH and LH levels and ovarian oxidative stress, inflammatory, and apoptotic biomarkers, while decreasing serum AMH levels and α7nAChR gene expression. These changes were accompanied by marked ovarian histopathological alterations and increased caspase-3 immunoexpression. RIVA significantly attenuated the DOX-induced alterations in hormonal levels, α7nAChR gene expression, oxidative stress, inflammatory, and apoptotic biomarkers, with improvement in ovarian histopathology and reduction of caspase-3 immunoexpression. Overall, the protective effect of RIVA against DOX-induced ovarian injury was associated with modulation of α7nAChR/NF-κB/TNF-α/caspase-3 signaling, suggesting the involvement of this pathway in its protective effects (Fig. 1).

This study investigated the effects of subchronic exposure to Voliam Targo® (VT), a binary insecticide containing abamectin and chlorantraniliprole, on maternal reproduction, lactation, lipid metabolism, milk composition, and mammary gland integrity in female rabbits. Thirty nulliparous rabbits (30 females and 30 males; Oryctolagus cuniculus) were randomly assigned to control or VT-treated groups (15 mg/kg body weight/day by oral gavage) for 12 consecutive weeks. Following a 17-day pre-mating period, animals underwent artificial insemination using heterospermic or homospermic matings, with treatment maintained throughout gestation and lactation until postnatal day 35. Mammary gland alterations were evaluated using biochemical, histopathological, histomorphometric, and immunohistochemical analyses. VT exposure significantly increased maternal body weight during gestation and lactation while reducing mammary gland weight. Reproductive performance varied according to mating pattern, with paternal-only exposure increasing litter size, whereas biparental exposure produced the smallest litters and the highest maternal body weight during lactation. Early lactation was characterized by a transient increase in milk yield accompanied by decreased fat content and increased dry matter, protein, lactose, and pH. Lipid profiling demonstrated persistent hypercholesterolemia, intermittent hypertriglyceridemia, and progressive high density lipoprotein (HDL) elevation. Histopathological examination revealed acinar epithelial necrosis, inflammatory infiltration, fibrosis, ductal ectasia, and vascular congestion. Histomorphometry confirmed enlargement of acinar structures and epithelial nuclei, reflecting hypertrophy and architectural disorganization. Immunohistochemistry demonstrated increased Ki-67, p53, and Bcl-2 expression, suggesting dysregulated cell proliferation and apoptosis. These findings demonstrate that subchronic VT exposure compromises mammary gland integrity, lipid homeostasis, lactational function, and reproductive performance, highlighting potential reproductive health risks associated with chronic insecticide exposure.

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants increasingly linked to female reproductive toxicity. Among them, perfluorodecanoic acid (PFDA) has been implicated in ovarian dysfunction, yet the molecular basis of its ovotoxicity remains insufficiently defined. Here, we investigated PFDA-induced granulosa cell injury and examined whether kaempferol, a naturally occurring flavonoid, could mitigate these effects using an integrative approach combining network toxicology, single-cell transcriptomic projection, and in vitro validation. Computational analysis identified 121 shared targets among PFDA, kaempferol, and ovotoxicity-related gene sets, with enrichment in oxidative stress, inflammatory, and nuclear receptor-associated pathways. Single-cell projection of PFDA- and kaempferol-associated gene sets onto a human ovarian reference atlas localized these signatures across multiple ovarian cell populations, including granulosa cell clusters. In the human granulosa cell line HGrC1, PFDA significantly reduced cell viability, increased reactive oxygen species (ROS), impaired nuclear factor erythroid 2-related factor 2 (NRF2)-associated antioxidant defense, shifted apoptosis-related gene expression toward a pro-apoptotic profile, and suppressed steroidogenic gene expression. Co-treatment with kaempferol alleviated several of these changes, lowering ROS levels and partially restoring antioxidant and steroidogenic markers. Together, these findings indicate that PFDA disrupts granulosa cell homeostasis through redox imbalance and modulation of steroidogenesis-related gene expression, while kaempferol mitigates part of this response in the present in vitro model. This study provides mechanistic insight into PFDA-induced granulosa cell toxicity and supports further investigation of bioactive flavonoids as modulators of pollutant-related ovarian injury.

Advanced glycation end products (AGEs), prevalent in Western thermally processed diets, contribute to metabolic dysfunction, oxidative stress, and impaired male reproduction; however, their effects on testicular RNA methylation remain unclear. This study investigated the effects of a 20-week high-fat, AGE-rich diet compared with a standard diet on global m[6]A RNA levels and m[6]A regulatory proteins in testicular tissue of male C57BL/6 mice (n = 6/group). Molecular analyses were performed exploratorily in a randomly selected subset of three animals per group using archived testicular tissue from the original experiment. Phenotypic outcomes, including metabolic indices, organ weights, sperm parameters, oxidative stress markers, and sperm chromatin/DNA integrity, were obtained from the primary study. Global m[6]A RNA content was measured in total RNA, and METTL14, ALKBH5, FTO, and YTHDF2 protein levels were assessed in the same exploratory subset. Statistical analyses were conducted using GraphPad Prism 10.4.0, with appropriate parametric or nonparametric tests and significance set at P < 0.05. The high-fat, AGE-rich diet induced metabolic disturbance, impaired sperm quality, increased oxidative stress, histone retention, DNA damage, and altered testicular redox balance (P < 0.05). It also significantly reduced global testicular m[6]A RNA levels and METTL14 expression while increasing ALKBH5 and YTHDF2 expression (P < 0.05). FTO reduction was not statistically significant (P > 0.05). Overall, high-fat, AGE-rich dietary exposure was associated with reproductive dysfunction and disrupted testicular m[6]A RNA methylation homeostasis, suggesting that altered m[6]A regulation may be a potential molecular mechanism underlying male reproductive impairment.

Environmental particulate matter pollution is commonly associated with adverse pregnancy outcome, and impaired trophoblast development and function; however, the underlying biological mechanisms remain poorly understood. This meta-analysis aims to investigate the detrimental effects of particulate matter on cell viability, gene and protein expression pathways in trophoblast cells in vitro by systematically searching Google Scholar, PubMed, CENTRAL, Embase, CINAHL, MEDLINE for articles published up to September 2025. Pooled relative risks (RR) with 95% confidence intervals (CIs) were calculated to evaluate the gene and protein expression on exposure to PM2.5. Of 1506 records screened, 12 studies were selected based on the inclusion criteria. Results showed PM2.5 reduces cell viability collectively by 20.68%, disrupts steroidogenic enzymes (CYP11A1, 3β-HSD1, FDXR) separates hCG production from progesterone synthesis, further exacerbating inflammatory signalling. PM2.5 induces oxidative stress that further causes DNA damage, activating ATR-mediated p53-independent apoptosis. Angiogenic signalling through VEGF-VEGFR2-MEK-ERK-mTOR is supressed due to PM2.5 exposure. Matrix remodelling is also impaired due to the dominant TIMP expression, RhoA dysregulation, and Collagen I loss by collectively reducing migration, and invasive capability of the trophoblast cells. Overall, this meta-analysis underscores the underlying mechanisms by which PM2.5 consistently impairs trophoblast function and contributes to placental dysfunction.

Microplastics and nanoplastics (MNPs) have emerged as widespread environmental contaminants with increasing relevance to human health. Accumulating experimental evidence indicates that the male reproductive system is a potential target of MNPs toxicity, with reported effects on spermatogenesis, steroidogenesis, blood-testis barrier (BTB) integrity, and testicular inflammatory homeostasis. In this review, we summarize current evidence on human exposure, systemic distribution, and the testicular fate of MNPs, and critically evaluate their effects on germ cells, Sertoli cells, Leydig cells, and resident immune cells. Available studies suggest that nanoscale plastic particles can reach the testis under experimental conditions, whereas both micro- and nanoplastics may compromise BTB integrity. Oxidative stress and mitochondrial dysfunction emerge as recurrent upstream events linking MNP exposure to cGAS-STING signaling, inflammatory cell death, impaired steroidogenesis, and macrophage activation. NF-κB and p38 MAPK signaling, M1-like macrophage polarization, and gut microbiota-associated IL-17A responses may further amplify testicular inflammation. However, current mechanistic evidence is derived predominantly from rodent models and oral exposure paradigms, and its relevance to human reproductive health remains incompletely defined. Further studies using diverse mammalian models, environmentally relevant exposures, and cell-resolved particle tracing are needed to clarify the reproductive consequences of MNP exposure.

Cetylpyridinium chloride (CPC) is a prevalent disinfectant utilized as an antimicrobial agent at millimolar concentrations in numerous products directly applied to humans. Recently, CPC has been documented to have detrimental effects on female reproduction. Nevertheless, the precise mechanisms through which CPC impairs mammalian oocyte quality and the corresponding protective interventions remain inadequately elucidated. In this study, we identified that CPC can hinder oocyte maturation in vitro at nanomolar concentrations. Mechanistically, CPC disrupts spindle morphology and chromosome alignment and reduces α-tubulin acetylation levels, impairing oocyte developmental competence. Furthermore, CPC exposure altered mitochondrial distribution and intracellular Ca[2+] homeostasis, while non-significant trends toward increased TMRE fluorescence and reduced ATP content were observed. These changes are associated with excessive ROS accumulation and DNA damage, which may act as downstream amplifiers of CPC-induced toxicity, ultimately triggering early apoptosis in oocytes. Melatonin, the primary hormone secreted by the pineal gland, is recognized as a free radical scavenger and antioxidant. We observed an association between melatonin supplementation and partial amelioration of spindle-chromosome abnormalities, redox imbalance and mitochondrial dysfunction in CPC-exposed oocytes. In conclusion, these findings illustrate that nanomolar concentrations of CPC used in vitro studies have potential harmful effects on mammalian oocyte quality. This study provides insights into potential mechanism underlying melatonin treatment against oocyte damage.

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants widely detected in human biological matrices, including placenta and umbilical cord blood, indicating early-life exposure. Perfluorooctanoic acid (PFOA), one of the most prevalent PFAS, has been associated with endocrine disruption and adverse reproductive outcomes. However, most toxicological studies rely on high-dose exposure models that do not reflect real-world conditions, limiting translational relevance. This study evaluated the effects of gestational exposure to environmentally relevant doses of PFOA during organogenesis on maternal toxicity and embryofetal development in Wistar rats. Pregnant females were orally exposed from gestational day (GD) 6-15 to control, 10, 100, or 1000 µg/kg/day PFOA. On GD20, maternal and fetal parameters were assessed. PFOA exposure induced subtle maternal effects, including reduced gestational weight gain at the highest dose and biochemical alterations such as decreased total protein and uric acid levels, alongside increased calcium concentrations. Despite limited maternal toxicity, significant developmental alterations were observed. Notably, fetal growth patterns were altered, with a shift from AGA toward LGA at the intermediate dose in both sexes, suggesting a potential non-monotonic dose-response pattern. Structural analyses revealed congenital cardiomegaly and skeletal abnormalities, including supernumerary ribs, incomplete ossification, and sternal agenesis. These findings demonstrate that gestational exposure to environmentally relevant PFOA doses during organogenesis induces developmental toxicity even in the absence of overt maternal toxicity. Although these results are consistent with the concept that early developmental windows are highly sensitive to environmental contaminants, postnatal and long-term evaluations are required to determine whether these embryofetal changes persist or translate into later-life functional outcomes.

The progressive deterioration of human male reproductive capacity has paralleled the mounting global dispersal of persistent organic pollutants (POPs) and plastic-associated contaminants. Nevertheless, the collective consequences of simultaneous exposure to these ubiquitous environmental stressors on spermatozoal function remain inadequately characterized. This study undertook a comprehensive evaluation of the interactive reproductive harm posed by 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and 25 nm polystyrene nanoplastics (PS-NPs) on human spermatozoa. Whereas isolated challenges with ecologically pertinent doses of either BDE-47 or PS-NPs yielded negligible alterations in sperm viability and motility parameters, concurrent administration provoked a marked superadditive compromise of multiple functional attributes indispensable for successful fertilization. Co-treatment substantially attenuated both total and progressive motility, diminished the penetrative capacity through a cervical mucus surrogate, and abrogated the induction of capacitation and progesterone-induced acrosome reaction. Mechanistic elucidation uncovered that dual exposure synergistically intensified intracellular reactive oxygen species accumulation and profoundly destabilized mitochondrial membrane potential, culminating in a robust augmentation of apoptotic rates. Furthermore, convergent network pharmacology assessments pinpointed pivotal signaling hubs governing apoptosis, including Caspase-3 and constituents of the BCL-2 family members, as principal mediators of the combined toxic insult. Collectively, these findings provide direct evidence that PS-NPs function as potent vectors capable of amplifying the spermatotoxicity of BDE-47 via a cascade of oxidative imbalance, mitochondrial dysfunction and programmed cell death initiation. This work highlights the imperative for adopting mixture centric frameworks in environmental contaminant hazard evaluation and yields novel mechanistic perspectives regarding the plausible etiological role of pollutant co-exposure to idiopathic male infertility.

Airborne contaminants represent a significant environmental health concern for vulnerable populations, including pregnant individuals. In particular, maternal inhalation of particulate matter (PM) during pregnancy has been linked to adverse outcomes such as fetal growth restriction (FGR). Increasing evidence identifies placental dysfunction as a mechanism for this condition. Placental efficiency, defined as the ratio of fetal mass to placental mass, is frequently altered in FGR. Many aspects contribute to placental efficiency including surface area available for nutrient and waste exchange and placental vascularization. In this study, we hypothesized that maternal inhalation of ultrafine PM during pregnancy would reduce the size and/or number of placental structures that are necessary for nutrient transport. Engineered titanium dioxide nanoparticles (nano-TiO2) were used as a proxy for ultrafine PM and pregnant Sprague Dawley rats were exposed via whole-body inhalation to nano-TiO2 aerosols (9.23 ± 0.39 mg/m[3]) from gestational day (GD) 5-19. On GD 20, placentas were collected and processed for histological evaluation. While gestational inhalation of nano-TiO2 did not affect placental weight or efficiency, it reduced decidua and labyrinth zone size. Exposed placentas exhibited compensatory adaptations characterized by increased blood space number and maternal blood space expansion. Together, these findings indicate that inhalation of nanoparticles disrupts placental structure while simultaneously eliciting changes in vascular architecture that may preserve nutrient exchange capacity. By characterizing the effects of PM exposure on placental morphology and structure, this study highlights the placenta as a vulnerable target of inhaled pollutants and provides mechanistic insight into pathways contributing to PM-induced FGR.