Farah Hanan Fathihah Jaffar

Background: Diabetes mellitus is characterized by chronic hyperglycemia, which promotes oxidative stress and endothelial dysfunction. MicroRNAs (miRNAs) have emerged as important regulators of diabetic vascular complications. Our previous RNA-sequencing study identified putative novel miR-1133 as an upregulated miRNA in hyperglycemia-induced human umbilical vein endothelial cells (HUVECs). This study aimed to investigate the potential involvement of putative novel miR-1133 in oxidative stress in hyperglycemia-induced HUVECs. Methods: Functional enrichment and protein–protein interaction (PPI) network analyses were performed to identify biologically relevant predicted target genes of putative novel miR-1133. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) was selected for further investigation because it was identified as a hub gene in the PPI network and was involved in the enriched PI3K/Akt signaling pathway. HUVECs were exposed to high glucose (33.3 mM) to establish an in vitro hyperglycemic model, and the effects of transfection with putative novel miR-1133 inhibitor on PIK3CA expression and oxidative stress markers were evaluated. Results: Bioinformatic analyses identified PIK3CA as a hub gene among the predicted targets of putative novel miR-1133 and identified the PI3K/Akt signaling pathway as significantly enriched. Experimentally, hyperglycemia significantly reduced PIK3CA expression, whereas putative novel miR-1133 inhibitor transfection increased PIK3CA expression. Furthermore, putative novel miR-1133 inhibitor transfection was associated with reduced reactive oxygen species and 8-hydroxy-2′-deoxyguanosine levels, together with increased superoxide dismutase 1 (SOD1) mRNA expression and total SOD activity. Conclusions: Transfection with putative novel miR-1133 inhibitor was associated with increased PIK3CA expression and reduced oxidative stress markers in hyperglycemia-induced endothelial cells. Together, bioinformatic and experimental findings support an association between putative novel miR-1133 inhibitor transfection, PIK3CA expression, and oxidative stress under hyperglycemic conditions. Further studies are required to validate the direct interaction between putative novel miR-1133 and PIK3CA and to determine the relevance of these findings in vivo.

Diabetes mellitus induces endothelial dysfunction and oxidative stress, contributing to the development of vascular complications. Although metformin exerts well-established vasculoprotective and antioxidant effects, the molecular mechanisms underlying these actions remain incompletely understood. Novel miR-1133 was previously identified as a metformin-responsive putative microRNA (miRNA), and bioinformatic analysis identified PIK3CA as a biologically plausible candidate target for further investigation. This study investigated the functional significance of novel miR-1133 in the antioxidant effects of metformin in hyperglycemia-induced human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to normal glucose (5.5 mmol/L), hyperglycemia (33.3 mmol/L), or hyperglycemia supplemented with metformin (10 μM) for 24 h. Metformin-treated hyperglycemic HUVECs were subsequently transfected with a novel miR-1133 mimic during continued hyperglycemic and metformin exposure. PIK3CA expression and oxidative stress markers, including reactive oxygen species (ROS), superoxide dismutase (SOD), and 8-hydroxy-2′-deoxyguanosine (8-OHdG), were evaluated. Hyperglycemia increased novel miR-1133 expression, whereas metformin reduced its expression. Metformin treatment was associated with increased PIK3CA mRNA and protein expression, reduced ROS and 8-OHdG levels, and increased SOD expression and activity. Novel miR-1133 mimic transfection was associated with reduced PIK3CA expression, increased ROS and 8-OHdG levels, and decreased SOD expression and activity compared with the corresponding transfection control. Collectively, these findings demonstrate that metformin attenuates oxidative stress in hyperglycemia-induced endothelial cells and overall provide the first functional characterization of novel miR-1133. The reciprocal changes in PIK3CA expression and oxidative stress observed following novel miR-1133 mimic transfection suggest that novel miR-1133 may represent a candidate mediator of the endothelial antioxidant responses associated with metformin. Further studies are required to validate the direct interaction between novel miR-1133 and PIK3CA and to elucidate the underlying molecular mechanisms.

The rapid expansion of 5G technology has increased exposure to high-frequency radiofrequency electromagnetic fields (RF-EMF), raising concerns about male reproductive health. This study investigated the effects of 5G frequencies at 3.5 GHz and 24 GHz on male libido, reproductive hormones, the testosterone-to-oestrogen (T/E) ratio, and androgen receptor expression in rats. Eighteen male Sprague–Dawley rats were randomly assigned to Control, 3.5 GHz, and 24 GHz (n = 6/group). Exposed groups received 7 h/day RF-EMF exposure for 60 consecutive days, while the Control underwent sham exposure. During the final week of exposure, mating behaviours were assessed using mount frequency, mount latency, intromission frequency, ejaculation latency, and post-ejaculatory interval. Serum testosterone and oestrogen levels, the T/E ratio and androgen receptor expression in the testis and hypothalamus were evaluated. The 3.5 GHz group demonstrated statistically significantly prolonged ejaculation latency (3480 ± 1576.956, p < 0.01, Hedges’ g = 1.03) compared with the Control group. In contrast, 24 GHz exposure statistically significantly reduced mount frequency (4.80 ± 0.837, p < 0.01, Hedges’ g = −0.65) and prolonged the post-ejaculatory interval (588.83 ± 206.41 s, p < 0.01, Hedges’ g = 1.63) compared with the Control group. Hormonal analysis revealed statistically significant elevation of testosterone levels in the 3.5 GHz group, whereas the 24 GHz group showed statistically significant reductions in testosterone and oestrogen. Androgen receptor expression was unchanged. These findings suggest frequency-dependent effects of 5G RF-EMF on male libido and endocrine balance.

Background and objectives: The advancement of 5G technology is highly anticipated due to its faster data transmission, yet its potential impact on male fertility remains unclear. This study evaluated the effects of 5G frequencies at 3.5 GHz and 24 GHz on sperm parameters, mating success, and offspring outcomes. Methods: A total of 18 male Sprague Dawley rats (n=18) were divided into three groups: a Control group, a 3.5 GHz group, and a 24 GHz group (n=6). The Control group was sham-exposed. In contrast, the 3.5 GHz and 24 GHz groups were exposed to their respective frequencies for 7 h daily over 60 d. Following 46 d of exposure, a 1:1 mating procedure was conducted. Female rats (n=18) were monitored until gestation d 28 to assess pregnancy rates and birth metrics. Later, the male rats were sacrificed, and sperm quality was evaluated. Results: Both exposed groups exhibited a significant decrease in sperm concentration and motility ( P P < 0.001). Interpretation and conclusions: The findings suggest prolonged exposure to 5G frequencies may have a negative impact on male fertility, pregnancy outcomes, and the birth metrics.

Bees are social insects belonging to the Apidae family, which includes stingless bees, honeybees, and related groups. Their ability to produce various products, such as bee bread, bee pollen, propolis, beeswax, and royal jelly, has attracted scientific interest due to their nutritional composition, biological activities, and potential therapeutic value. Bee bread is a fermented mixture of pollen, honey, and salivary bee enzymes, rich in bioactive compounds with potential benefits for reproductive health and other biological activities. However, bee bread remains one of the least explored bee products in relation to reproductive health. This narrative review summarises the potential health benefits of bee bread from stingless bees for male and female reproductive function. Evidence from animal studies shows that bee bread has promising effects on reproductive function, possibly through its antioxidant properties, support of spermatogenesis and steroidogenesis, improvement of pregnancy outcomes, enhancement of ovarian function, regulation of metabolism, and modulation of inflammatory activity. Findings from animal studies suggest potential benefits for both male and female reproductive health. However, well-designed randomised controlled trials are needed to evaluate its efficacy, optimal dosage, safety profile, and long-term effects on reproductive outcomes in both males and females.

The brain and testes are connected via the hypothalamic–pituitary–gonadal (HPG) axis. Both are vulnerable to radiofrequency electromagnetic radiation (RF-EMR). However, no comprehensive study had evaluated the effects of RF-EMR on key hormones along this axis. Hereby, this study evaluated the effect of RF-EMR on the hormonal changes along the axis, including the neuropeptide kisspeptin. A total of 18 (N = 18) adult Sprague–Dawley rats were divided into three groups (n = 6): Control, 4 h, and 24 h. The Control group was sham-exposed to an inactive router. The exposed groups were subjected to 2.45 GHz RF-EMR for 4 and 24 h daily, for 60 days at a 20 cm distance. The power density was 0.141 W/m² with a whole-body specific absorption rate (SAR) of 0.41 W/kg. No significant changes were observed in hypothalamic Kiss1 gene expression or serum kisspeptin levels. GnRH levels increased significantly in both exposed groups, while FSH and LH remained unchanged. Testicular testosterone was significantly reduced in the 24 h group, while serum testosterone was elevated in the 24 h group compared to the 4 h group. In conclusion, prolonged 2.45 GHz RF-EMR exposure caused selective changes in components of the HPG axis, particularly involving GnRH and testosterone, suggesting potential endocrine effects on male reproductive regulation.

The expansion of fifth-generation (5G) wireless networks has increased environmental exposure to mid-band and millimeter-wave radiofrequency electromagnetic fields (RF-EMF), but their molecular effects on male reproductive tissues remain insufficiently understood. This study evaluated whether repeated exposure to 3.5 GHz and 24 GHz RF-EMF alters testicular stress-associated molecular responses by integrating electromagnetic dosimetry with an in vivo rat model. Whole-body specific absorption rate (SAR) and 10 g peak SAR were estimated using a rat voxel model and scaled to the 20 cm antenna-to-cage geometry used during exposure. Thirty-six adult male Sprague Dawley rats were allocated to sham, 3.5 GHz, or 24 GHz groups and exposed for 1 h/day or 7 h/day over 60 days. Testes were examined histologically and assessed for HSP27, HSP70, and HSP90 protein expression. SAR values were low overall, although absorption was higher at 3.5 GHz than at 24 GHz. Histological evaluation showed preserved seminiferous tubule architecture without consistent structural injury. In contrast, molecular analysis demonstrated frequency- and duration-dependent modulation of heat shock proteins, including early HSP70 downregulation at both frequencies, followed by HSP90 upregulation at 3.5 GHz and HSP27 upregulation at 24 GHz. These findings indicate that low-level 5G-relevant RF-EMF exposure can modify molecular stress responses in testicular tissue even in the absence of overt histological damage.

Edible bird nest (EBN) has a longstanding tradition in Chinese herbal medicine as a natural supplement for enhancing health and well-being. Current scientific research indicates that EBN possesses properties conducive to improving male reproductive function. These properties include promoting cell proliferation, containing essential reproductive hormones, and exhibiting antioxidant activity. Despite these promising characteristics, the potential of EBN’s specific effects on male reproductive health, particularly in addressing infertility, remains sparsely discussed. Hereby, this review aims to present the available scientific evidence, discuss potential benefits, and underscore the importance of future research in advancing our understanding of EBN’s role in male reproductive health. This work is imperative to expand our knowledge of the biological underpinnings of EBN so that it can be developed as a food supplement and alternative treatment for male infertility.

Background/Objectives: The rapid rollout of 5G has renewed interest in potential reproductive effects of mid-band (3.5 GHz) and millimeter-wave (24 GHz) radiofrequency electromagnetic fields (RF-EMF). We examined frequency- and duration-dependent changes in testicular cytokines, apoptosis-related genes, and sperm quality in rats. Methods: Male Sprague Dawley rats (n = 6 per group) were exposed for 60 days to 3.5 GHz or 24 GHz RF-EMF for 1 h/day or 7 h/day. The sham controls were housed identically. Testicular expressions of IL-10, IL-6, IL-1β, and TNF-α were quantified; Tp53, Bax, Bcl2, and Casp3 mRNA expressions were measured; and sperm concentration, viability, and motility were evaluated. Results: IL-10 was significantly reduced in the 24 GHz group at both 1-h and 7-h exposure duration. At 7 h, TNF-α was also lower at 24 GHz. Casp3 expression was higher and Tp53 was lower at 3.5 GHz at 1-h exposure duration. Sperm concentration and viability were reduced after 24 GHz exposure at 7 h, while sperm motility was reduced after 3.5 GHz exposure at both durations. Conclusions: Exposure to RF-EMF 3.5 GHz primarily impacts sperm motility via extrinsic pro-apoptotic pathways, while exposure to 24 GHz impacts sperm concentration and viability potentially through immune–apoptotic mechanisms, with all negative effects amplified by 7-h daily exposure.

The adenosine monophosphate (AMP)-activated protein kinase (AMPK) signalling pathway regulates cell metabolism, inflammation and the immune response. This signalling pathway is essential for maintaining reproductive homeostasis and influencing steroidogenesis, implantation, and embryonic development. The central sensor, AMPK, regulates cell function in response to metabolic stress. The dysregulation of AMPK signalling has been implicated in several female reproductive disorders, including polycystic ovary syndrome (PCOS), endometriosis, infertility, and reproductive ageing. This review provides an overview of the role of AMPK in reproductive function and disorders, as well as potential therapeutic targets to restore balance in this signalling pathway. It discusses AMPK signalling in folliculogenesis, oocyte maturation, pregnancy maintenance, pre-eclampsia (PE) pathogenesis, PCOS, preterm birth, endometriosis, dysmenorrhoea and other disorders related to female reproduction. A deeper understanding of AMPK signalling in these contexts could provide new insights for the development of therapeutic interventions for reproductive health.