Zanjan University of Medical Sciences

Prenatal and early-life stress (ELS) reprogram the hypothalamic-pituitary-adrenal (HPA) axis and intersecting neurotransmitter circuits, producing long-lasting alterations in the oxytocin (OXT) system. Accumulating clinical and pre-clinical evidence links these neurobiological changes to increased vulnerability for addiction. This narrative review synthesizes recent (2005–2025) literature on: how ELS disrupts the maturation of OXT neurons and receptors; the consequent cross-talk with glutamatergic, GABAergic and HPA-peptide signaling that biases the mesocorticolimbic reward network toward addiction; and the emerging therapeutic potential of exogenous OXT. Rodent models of maternal separation, limited bedding or gestational restraint reveal OXT-system hypofunction—marked by OXTR hyper-methylation, reduced hypothalamic OXT mRNA and diminished receptor density in the amygdala and nucleus accumbens. Parallel human studies report analogous epigenetic signatures in cord blood and peripheral tissues of stress-exposed offspring. Functionally, OXT curtails presynaptic glutamate release in the ventral tegmental area, augments tonic GABA_A currents in medial prefrontal cortex, and attenuates AVP-driven CRH output, thereby normalizing reward- and stress-circuit activity. These adaptations translate into lower drug intake, reduced cue-induced reinstatement and blunted withdrawal anxiety in animal models. Early clinical trials corroborate these findings; intranasal OXT reduces craving and withdrawal severity, with the largest effect sizes observed in individuals exhibiting low baseline plasma OXT or high OXTR methylation. It can be concluded that prenatal stress is a potent risk factor for later substance use disorders (SUDs), in part via durable disruption of the developing OXT system. Targeted OXT pharmacotherapy—alone or combined with stress-axis modulators—holds promise for a precision-medicine approach to addiction, particularly in ELS-exposed subpopulations.

Infertility is a crucial challenge for global health that encompasses economic, psychological, and medical aspects. Besides anatomical contributors to infertility, specific dietary components may influence reproductive outcomes in both men and women through diverse molecular and epigenetic mechanisms. This study aimed to evaluate the role of macronutrients, vitamins, and minerals in male and female infertility using a system biology approach. To address the complex interplay between infertility and nutritional factors, we focused on published studies that explore molecular and systems biology pathways, including those involving nutrigenetics, epigenetics, metabolomics, and gene expression profiling. These studies span both human and animal models and were selected based on their relevance to reproductive outcomes and mechanistic insights. Several nutrients appear to influence infertility through distinct molecular mechanisms. Polyunsaturated fatty acids (PUFAs) may exert beneficial effects by modulating the expression of fertility-related genes, while saturated fatty acids (SFAs) are associated with impaired oocyte quality and reproductive dysfunction via altered gene expression and DNA damage. Among micronutrients, increased intake of folate and vitamin D has been linked to improved gamete quality and folliculogenesis in women with infertility. Dietary glutamine and selenium may enhance fertility through their antioxidant properties. Iron demonstrates dual effects, potentially supporting or impairing fertility depending on its role in epigenetic regulation. Dietary intake may influence the risk of infertility through pathways related to nutrigenetics, nutrigenomics, and nutri-epigenomics. While current evidence suggests promising nutrient–gene interactions, most findings are derived from small-scale or preclinical studies, highlighting the need for robust human trials.

Freezing of gait is a disabling and treatment-resistant manifestation of Parkinson’s disease (PD). The effectiveness of deep brain stimulation (DBS) for freezing of gait remains inconsistent across stimulation targets, frequencies, and medication states. We conducted a systematic review and meta-analysis following PRISMA guidelines to examine how DBS affects freezing of gait in patients with PD. We searched Medline, Scopus, Web of Science, and Cochrane up to September 28, 2025. For synthesis, we combined mean differences and 95

Introduction Numerous lifestyle factors contribute to the incidence of infertility, which is a major concern for couples throughout the globe. The effectiveness of in vitro fertilization (IVF) is highly dependent on the characteristics of the culture media used.Objective The present research study aimed to determine the effects of L-aspartic acid, L-ascorbic acid, and silver nanoparticles (AgNPs) on the success rate of IVF in NMRI mice.Methods The solutions of L-aspartic acid, L-ascorbic acid, and synthesized AgNPs were prepared. The 6-8 weeks-old NMRI male mice were used as sperm donors, and 6-8 weeks-old NMRI mice were used for oocyte donation. In addition, the IVF procedure was performed using 50 mu L drops of KSOM+5%BSA in mineral oil. Seven different experimental groups were investigated in addition to the control group. Oocytes were exposed to sperm for 4-6 h in the KSOM medium as a control group.Results and Discussion According to the results, the groups containing supplements "AgNPs", "L-aspartic acid", and "AgNPs + L-ascorbic acid", were not suitable for the 2PN stage. In contrast, the group containing "L-aspartic acid + L-ascorbic acid" was the best group for the 2PN stage. In addition, supplementation of the mixture of L-aspartic acid and AgNPs solution in KSOM+BSA culture medium was the most suitable group for the 2Cell stage.Conclusion In conclusion, the study highlighted the varying impacts of L-aspartic acid, L-ascorbic acid, and AgNPs on IVF outcomes in NMRI mice. Group E, combining L-aspartic acid and AgNPs, emerged as effective for 2Cell development. Future research should explore the underlying biochemical mechanisms of these findings. Furthermore, another study is in progress that utilizes these supplements to generate 2PN first, and then the supplement-free medium as the cleavage media.

Lead exposure is linked to various adverse effects on human health, including toxicity to multiple organs such as the kidneys, liver, and reproductive system. Lead induces its toxic effects through complex pathways, including mitochondrial dysfunction, oxidative stress, and inflammation. Hydrogen-rich water (HRW) has emerged as a promising therapeutic agent due to its ability to modulate redox homeostasis via regulating mitochondrial ROS production. This study aimed to evaluate the efficacy of HRW, alone and in combination with Ethylenediaminetetraacetic acid (EDTA), in alleviating the complications of acute lead poisoning in an animal model. Thirty male Wistar rats were divided into five groups: control, lead acetate (PbA), EDTA treatment, HRW treatment, and combination of HRW and EDTA. PbA was administered via intraperitoneal injection, while HRW was given through oral gavage. After one week of treatment, body weight, organ weights (liver, kidney, and testis), serum measurements, histopathological evaluations and oxidative-stress marker, malondialdehyde (MDA), and antioxidative-stress factors including superoxide dismutase (SOD) and catalase in liver, kidney, and testis were assessed. Lead acetate exposure caused systemic and organ-specific toxicity, characterized by weight loss by approximately 13