Wasim Bari

Cellular memory, or epigenetic memory, represents the capacity for cells to retain information beyond the underlying DNA sequence. This heritable characteristic is primarily governed by epigenetic mechanisms which enable cells to maintain specialized characteristics across divisions. This persistent cellular state is essential for fundamental biological processes, such as maintaining tissue identity and facilitating cell differentiation, especially embryonic cells. Early-stage perturbations such as assisted reproductive technologies (ART) and nutritional stress links embryonic exposures to adult health and disease within the Developmental Origins of Health and Disease (DOHaD) framework. Crucially, memory established during early embryogenesis links these epigenetic modifications to adult long-term phenotypes related to metabolic disorders. These modifications—including DNA methylation, histone modifications, and non-coding RNAs—support cellular memory transmission across cell divisions, and in certain organisms, can be transmitted across generations without alterations to the DNA sequence. This review synthesizes recent advances in epigenetic pathways that mediate cellular memory, highlights critical preimplantation windows of vulnerability and outlines gaps necessary for mammalian developing interventions that safeguard future generations.

Background: Lysosomes serve not only in the degradation of cellular components but also as calcium (Ca2+) stores. In this study, we investigated the effects of trans-Ned19, an inhibitor of lysosomal calcium channels known to block two-pore channels (TPCs), on fertilization and oocyte activation in mice. Methods: Pronuclear formation was assessed via Hoechst 33342 staining, cortical granule release was evaluated using Lens culinaris agglutinin-fluorescein isothiocyanate (LCA-FITC) staining, intracellular Ca2+ levels were monitored with Cal-520 AM, and sperm motility was analyzed using a sperm motility analysis system (SMAS). Results: In strontium (Sr2+)-induced oocyte activation, trans-Ned19 significantly reduced pronuclear formation at 8 h post-activation. Cortical granule release and Ca2+ oscillations were also markedly suppressed. In contrast, during in vitro fertilization (IVF), trans-Ned19 treatment significantly decreased the fertilization rate; however, pronuclear formation and cortical granule release remained comparable to controls in fertilized embryos. Notably, when IVF was performed using zona pellucida-free oocytes, the fertilization rate in the trans-Ned19 group was similar to that of the controls. However, a significant increase in polyspermy was observed. Furthermore, trans-Ned19 significantly impaired sperm motility parameters, including straight-line velocity, curvilinear velocity, and average path velocity. Conclusions: These findings suggest that lysosomal TPCs are essential for both normal fertilization and artificial oocyte activation in mice.

Bovine serum albumin (BSA), the most commonly used protein in preimplantation embryo culture media, performs a variety of physiological functions. However, its involvement in long-term effects remains largely unclear. To investigate its physiological importance in culture media, we examined the developmental and metabolic consequences of BSA deprivation during preimplantation stages in mice. Embryos cultured in BSA-free media during specific time windows exhibited impaired blastocyst formation, with continuous deprivation from the two-pronuclei (2PN) stage significantly reducing trophectoderm (TE) and inner cell mass (ICM) cell numbers (p < 0.05), indicating compromised viability. Short-term BSA deprivation similarly disrupted lineage allocation, underscoring the sensitivity of early embryos to nutrient availability during cell fate determination. Although birth rates remained unaffected, suggesting compensatory mechanisms, longitudinal analysis revealed sex-specific metabolic dysfunction. Male offspring developed progressive glucose intolerance by 16 weeks, exhibiting elevated fasting glucose levels (p < 0.05) and impaired glucose clearance, whereas females showed no significant alterations in glucose metabolism. This study demonstrates that protein restriction during the preimplantation period not only disrupts early embryonic development but also programs long-term metabolic dysfunction, underscoring the importance of optimizing culture conditions in assisted reproductive technologies to minimize future health risks.

Background: The metabolic syndrome (Met-S) is a cluster of some interrelated common clinical disorders, including central obesity, dyslipidemia, hypertension, and glucose intolerance. Central obesity, accompanied by insulin resistance, is a key factor for the development of metabolic syndrome. Adiponectin is an adipose-specific plasma protein, secreted from adipocyte with anti-atherogenic and insulin-sensitizing activities. Purpose: This study aimed to investigate the relationship of plasma adiponectin levels with metabolic syndrome, related disorders and its drug repurposing through in silico approach. Materials and Methods: For this study, 269 individuals were recruited with written consent. The participants were selected based on their full medical history, clinical examination, and laboratory reports. Anthropometric measurements as well as blood pressure was measured before sample collection. Fasting blood samples were collected for the estimation of lipid profile, blood glucose, and serum adiponectin levels. Results: Our results show that the adiponectin levels in the subjects with Met-S were significantly lower than those of without Met-S (p <0.0001). Among the metabolic syndrome risk factors, adiponectin levels were associated with hypertriglyceridemia and reduced HDL-cholesterol (p<0.0001). Three drugs (Saquinavir, Candesartan and Glimepiride) were suggested to control the plasma adiponectin level in the subjects with Met-S. Conclusions: Since the plasma adiponectin levels are significantly lower in patients with Met-S, it might be used as diagnostic & prognostic marker for Met-S disorder and adiponectin targeted drugs might be minimize the Met-S of the subjects.

In mammals, around fertilization, the nucleolus of embryos transforms into the nucleolus precursor bodies (NPBs), which continue to mature until the blastocyst stage, leading to distinct morphological changes. In our study, we observed two types of nucleolar morphology in mouse in vitro fertilized embryos at the four‐cell stage, which we refer to single nucleolus (SN) and multiple nucleoli (MN). To visualize nucleolar morphology, four‐cell embryos were immunostained with anti‐NOPP140 antibody. These embryos were categorized into five types based on the number of blastomeres carrying SN: SN4/MN0, SN3/MN1, SN2/MN2, SN1/MN3, and SN0/MN4, with percentages of 13, 27, 21, 23 and 9, respectively. Next, using a light microscope, we divided the four‐cell in vitro fertilized embryos without fixation into two groups: those with at least two blastomeres displaying SN (SN embryos) and those without (MN embryos). Notably, significantly more SN embryos developed into blastocysts and offspring at 18.5 dpc compared with MN embryos. Furthermore, SN embryos displayed a higher NANOG‐positive cell number at the blastocyst stage, significantly lower body and placental weights, resulting in a higher fetal/placental ratio. These findings suggest a close association between nucleolar state at the four‐cell stage and subsequent developmental potential.

Aims: The current study aimed to explore in vitro antioxidant capacity and in vivo antidiabetic property of Citrus maxima leaf. Methods: Citrus maxima leaf extracts were prepared using methanol (MECML) and ethanol (EECML) in this study. Antioxidant capacity of both extracts was evaluated using total antioxidant capacity (TAC) assay, ferric reducing antioxidant power (FRAP) assay, DPPH free radical scavenging assay, and ABTS free radical scavenging assay. Cytotoxicity of MECML and EECML was assessed by brine shrimp lethality bioassay. To explore the in vivo antidiabetic property of MECML and EECML, diabetic mellitus (DM) was induced in Swiss albino mice by a single intraperitoneal injection of alloxan. Then diabetic mice were treated with both extracts for 28 days. Effects of both extracts on serum levels of glucose, liver function enzymes, and parameters of lipid profile associated with DM were evaluated. Results: In TAC and FRAP assays, MECML and EECML represented gradually increased reducing capacity in a dose-dependent manner. In DPPH and ABTS assays, both extracts showed notable free radical scavenging activity with lower IC50 values. Additionally, MECML and EECML showed very low toxicity with LC50 values of 80.46 and 105.59 μg/mL, respectively in brine shrimp lethality assay. Moreover, both extracts significantly augmented altered levels of serum glucose, parameters of lipid profile, SGPT, SGOT, and C-reactive protein with the treatment of MECML and EECML. Conclusion: This study suggests Citrus maxima leaf possesses significant antioxidant and antidiabetic properties and they might play a potential role to prevent diabetic mellitus and diabetic mellitus associated complications.