Pubertal Rats Research Articles

Neonatal Sevoflurane Exposure Exerts Sex-Specific Effects on Cognitive Function via C3- and TLR4-Related M1/M2 Microglial Cell Polarisation in Rats.

In this study, we aimed to explore the sex-specific effects and mechanisms of sevoflurane exposure on the neural development of pubertal rats on the basis of M1/M2 microglial cell polarisation and related signalling pathways. A total of 48 rat pups (24 males and 24 females) were assigned to the 0- or 2-h sevoflurane exposure group on the seventh day after birth. The Morris water maze (MWM) test was subsequently conducted on the 32nd to 38th days after birth. M1/M2 microglial cell polarisation, C3 and TLR4 expression, and synapse growth were analysed within specific brain zones by immunofluorescence after the MWM test. We found that the negative effects caused by sevoflurane exposure were weaker in female rats than in male rats and had less influence on spatial memory. Sevoflurane exposure has opposite effects on microglial M1 polarisation in the different sexes but can promote M2 polarisation, with more obvious effects seen in female rats. In addition, sevoflurane exposure had bidirectional effects on C3 expression in different zones, while it clearly downregulated C3 expression in female rats. Moreover, sevoflurane decreased TLR4 expression in the hippocampus, whereas female rats exhibited better resistance, especially in the dentate gyrus. Compared with male rats, female rats were more resistant to the synaptic reduction effect of sevoflurane exposure. In conclusion, we found that neonatal sevoflurane exposure could exhibit sex-specific effects via the regulation of C3- and TLR4-related microglial cell polarisation. In addition, subregional regulation in the hippocampus might also contribute to its sex-specific effects.

Improving the Dehydroepiandrosterone Induced PCOS Rat Model: Interplay of Age, High Fat Diet, and Treatment Regimen on Reproductive and Metabolic Phenotypes

Polycystic ovary syndrome (PCOS) is a ubiquitous reproductive condition with triggering hallmarks such as glucose intolerance, hyperandrogenism, and dyslipidemia. Despite the existence of various PCOS animal models, an ideal model which could encompass all PCOS-specific phenotype is of dire need. Dehydroepiandrosterone (DHEA) induced PCOS rats are frequently employed; though, determining the superior model among pubertal and prepubertal rats, incorporation of high fat diet (HFD), and their sustainability remains uncertain. This study aims to examine the age factor, impact of HFD, and DHEA regimen in model development. Prepubertal and pubertal Sprague–Dawley rats were subcutaneously injected with DHEA (6 mg/kg and 60 mg/kg/day, respectively) with and without HFD up to 21 days. Serum testosterone, glucose, lipid profile, ovary morphology, and estrous cycle were evaluated. Following 21 days of treatment with DHEA, pubertal PCOS rats exhibited better reproductive phenotype than prepubertal rats. However, there was no significant difference in the lipid profile. Accordingly, both the age-group rats were concomitantly treated with DHEA and HFD for additional 3 weeks on alternate day basis after model development. The persistence of reproductive and metabolic features on treatment withdrawal were also simultaneously investigated by alienating the rats into continuous and stop dosing groups. The DHEA + HFD and DHEA treated pubertal rats in continuous dosing group showed significant PCOS features (p < 0.05) compared to stop dosing, prepubertal, and control groups. To conclude, continual dosing with DHEA on alternate days for 3 weeks is necessary to sustain metabolic and reproductive phenotypes of PCOS.

Peripubertal exposure to oxyfluorfen, a diphenyl herbicide, delays pubertal development in the male rat by antagonizing androgen receptor activity.

We recently identified the herbicide oxyfluorfen as an inhibitor of iodide uptake by the sodium iodide symporter (NIS), a key step in thyroid hormone synthesis, using in vitro assays. We also observed a suppression of serum T4 and T3 in juvenile rats exposed orally to oxyfluorfen for 4-8 days. The purpose of the present study was to further evaluate effects of an extended 31-day oral exposure using a male pubertal rat study (15 to 500 mg/kg). Oxyfluorfen delayed puberty at all doses (1.3 -3.5 days) suppressing ventral prostate at 62.5 mg/kg and above and seminal vesicle weights at 31.25 mg/kg and above with no effect on testosterone or luteinizing hormone. Serum T4 and T3 were suppressed by all doses up to 80%, with a linear increase in serum TSH. Based on delayed puberty without changes in testosterone, we hypothesized that oxyfluorfen interferes with androgen receptor (AR) function. Results from our Hershberger study, with oxyfluorfen (62.5 and 125 mg/kg) co-treated with testosterone proprionate (TP , 1 mg/kg) for 10 days showed 3 of 5 of the androgenic tissue weights were suppressed compared to TP alone indicating AR antagonism. We next confirmed this effect in an in vitro AR transcriptional activation reporter assay (0-20 μM) with 125 pM 5αDH-11-ketotestosterone and found concentration-dependent inhibition of AR luminescence activity (EC50 1.75 µM) without cytotoxicity. Here, we confirmed the endocrine disrupting effects of oxyfluorfen using both in vitro and in vivo evaluations of the thyroid hormone and AR pathways. This abstract doesn't necessarily reflect U.S. EPA policy.

Lisdexamfetamine dimesylate-exposition in male rats during the peripubertal period impairs inflammatory mechanisms, antioxidant activity, and apoptosis process in kidneys of male pubertal rats.

Lisdexamfetamine dimesylate (LDX) is a prodrug of dextroamphetamine, which has been widely recommended for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). There are still no data in the literature relating the possible toxic effects of LDX in the kidney. Therefore, the present study aims to evaluate the effects of LDX exposure on morphological, oxidative stress, cell death and inflammation parameters in the kidneys of male pubertal Wistar rats, since the kidneys are organs related to the excretion of most drugs. For this, twenty male Wistar rats were distributed randomly into two experimental groups: LDX group-received 11,3 mg/kg/day of LDX; and Control group-received tap water. Animals were treated by gavage from postnatal day (PND) 25 to 65. At PND 66, plasma was collected to the biochemical dosage, and the kidneys were collected for determinations of the inflammatory profile, oxidative status, cell death, and for histochemical, and morphometric analyses. Our results show that there was an increase in the number of cells marked for cell death, and a reduction of proximal and distal convoluted tubules mean diameter in the group that received LDX. In addition, our results also showed an increase in MPO and NAG activity, indicating an inflammatory response. The oxidative status showed that the antioxidant system is working undisrupted and avoiding oxidative stress. Therefore, LDX-exposition in male rats during the peripubertal period causes renal changes in pubertal age involving inflammatory mechanisms, antioxidant activity and apoptosis process.

Effects of Vaccination against Recombinant FSH or LH Receptor Subunits on Gonadal Development and Functioning Male Rats.

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) play key roles in regulating testosterone secretion and spermatogenesis in male mammals, respectively, and they maintain the fertility of male animals by binding to their corresponding receptors. We designed and prepared a recombinant LH receptor (LHR) subunit vaccine and a recombinant FSH receptor (FSHR) subunit vaccine and used male Sprague Dawley (SD) rats as a model to examine their effects on testicular development, spermatogenesis, and testosterone secretion in prepubertal and pubertal mammals. Both vaccines (LHR-DTT and FSHR-DTT) significantly decreased the serum testosterone level in prepubertal rats (p < 0.05) but had no effect on the testosterone secretion in pubertal rats; both vaccines decreased the number of cell layers in the seminiferous tubules and reduced spermatogenesis in prepubertal and pubertal rats. Subunit vaccine FSHR-DTT decreased the sperm density in the epididymis in both prepubertal and pubertal rats (p < 0.01) and lowered testicular index and sperm motility in pubertal rats (p < 0.05), whereas LHR-DTT only reduced the sperm density in the epididymis in pubertal rats (p < 0.05). These results indicate that the FSHR subunit vaccine may be a promising approach for immunocastration, but it still needs improvements in effectiveness.

Chlorocholine chloride exposure induced spermatogenic dysfunction via iron overload caused by AhR/PERK axis-dependent ferritinophagy activation

Chlorocholine chloride (CCC) is a plant growth regulator used worldwide that is detectable in cereals, fruits and animal products. The health effects of CCC exposure have raised public concern. Our previous research showed that CCC exposure decreased testosterone synthesis in pubertal rats. However, little is known about whether and how pubertal CCC exposure impacts spermatogenesis. In this study, we used BALB/c mice and spermatogonia-derived GC-1 cells to examine CCC-induced spermatogenic dysfunction. In vivo, pubertal CCC exposure led to decreased testicular weight, decreased testicular germ cells and poor sperm quality. This effect worsened after cessation of CCC exposure for the next 30 days. RNA-seq and western blot analysis revealed that CCC induced aryl hydrocarbon receptor (AhR) signaling, endoplasmic reticulum stress (ERS) and ferritinophagy. Increased iron content and lipid peroxidation levels were also observed in CCC-treated testes. In vitro, it was identified that iron overload mediated by enhanced ferritinophagy occurred in CCC-treated GC-1 cells, which might be attributed to the PERK pathway in ERS. Further, for the first time, our study elucidated the involvement of AhR in CCC-induced iron overload, which aggravated testicular oxidative damage via lipid peroxidation. Considering the adverse impact of CCC exposure on rodents, supportive evidence from GC-1 cells, and the critical importance of spermatogenesis on male development, the effects of CCC on the male reproduction warrant increased attention.

Embryonic and Neonatal Exposure to High-Fat Diet Disrupted Pancreatic Oxidative and Endoplasmic Reticulum Homeostasis Alongside Islet Insulin Output in Pubertal Rats

Embryonic and Neonatal Exposure to High-Fat Diet Disrupted Pancreatic Oxidative and Endoplasmic Reticulum Homeostasis Alongside Islet Insulin Output in Pubertal Rats

Morphine compromises androgen biosynthesis by immature Leydig cells from pubertal rat testes in vitro.

Morphine is an analgesic in the opiate family, isolated from many plants. It can inhibit androgen biosynthesis by Leydig cells. Whether morphine directly inhibits androgen biosynthesis and underlying mechanism remains unclear. To investigate the influence of morphine on androgen secretion by rat immature Leydig cells (ILCs) and possible mechanism. Rat ILCs were treated with 0.5-50μM morphine for 3h in vitro. Morphine at ≥0.5μM significantly reduced total androgen secretion. Morphine at 50μM also compromised luteinizing hormone (LH, 10mg/kg), 8Br-cAMP (1mM), and 22R-hydroxycholesterol (20μM) stimulated total androgen, androstanediol, and testosterone secretion, without affecting pregnenolone, progesterone, androstenedione mediated androgen secretion and testosterone and dihydrotestosterone mediated androstanediol secretion. Further analysis revealed that morphine at ≥0.5μM downregulated Star expression and at ≥5μM downregulated Cyp11a1 expression. Morphine also significantly reduced STAR (≥0.5μM) and reduced CYP11A1 (≥5μM) levels. 0.5μM naloxone significantly antagonized morphine-mediated action. In conclusion, morphine might cause side effects by suppressing androgen biosynthesis via u opioid receptor.

Mono-(2-ethylhexyl) phthalate (MEHP) reversibly disrupts the blood-testis barrier (BTB) in pubertal rats.

The blood-testis barrier (BTB) is constituted by tight junctions between adjacent Sertoli cells (SC) that create a specialized adluminal microenvironment to foster the development of spermatocytes and spermatids. The BTB is a well-studied target of numerous environmental toxicants, including di-(2-ethylhexyl) phthalate (DEHP), a compound widely used in various consumer products. MEHP is the active toxic metabolite of DEHP that has long been recognized in postnatal rodents to disrupt SC function. This study evaluates the impact of MEHP on the integrity of the BTB in both pubertal and adult rats and the signal transduction pathways known to be involved in the disruption of the BTB. Treatment of prepubertal rats with 700 mg/kg MEHP for 24 hours functionally disrupted the BTB integrity. A similar treatment of adult rats with MEHP did not disrupt the integrity of the BTB. The observed disruption of the BTB integrity in the MEHP-treated prepubertal rats occurred concomitantly with a decreased expression and mislocalization of both the ZO1 and occludin tight junction-associated proteins, as well as sloughing of spermatocytes and spermatids. At this same time, MEHP treatment induced a transient surge of p44/42 mitogen-activated protein kinase (MAPK) pathway. Interestingly, after a recovery period of 5 weeks, the BTB recovered and was functionally intact. This is the first report to indicate that acute MEHP exposure of prepubertal rats, but not adult rats, disrupts the functional integrity of the BTB and that this effect on the BTB is reversible.

Adipoz dokudan izole edilen mezenkimal kök hücrelerin donör yaşına bağlı olarak mTOR aktivitesinin belirlenmesi

Purpose: Aging in living organisms is an inevitable physiological consequence. Cellular senescence occurs not only in cells that have completed their differentiation, but also in stem cells. Mammalian target of Rapamycin protein complex (mTOR) has an important role in cell growth and metabolism. mTOR, which plays an important role in cell proliferation, also regulates cellular aging and directs the bionergetic infrastructure. The aim of the study is to determine the mTOR expression of mesenchymal stem cell (MSC) obtained from adipose tissue depending on the donor age.&#x0D; Materials and methods: 6-week-old pubertal rats were named Group 1 (n=6), 10-12-week-old reproductive period rats were named Group 2 (n=6), and 20-month-old rats were named Group 3 (n=6). MSC isolation was performed by primary explant culture method from adipose tissue taken from groups. Characterization and differentiation experiments were performed in MSC obtained. mTOR activity (mTORC1 and mTORC2) in MSC was determined by RT-PCR method. Caspase 3, 8, 9, Bax and Bcl-2 expressions were evaluated by RT-PCR method.&#x0D; Results: In our study, it was determined that the highest expression of apoptotic markers was in Group 1 and the lowest expression was in Group 2. When mTOR expression was evaluated, mTORC1 was found to be highest in Group 2 and lowest in Group 1. mTORC2 expression in Group 1 was lower than in other groups. Although the expression of mTORC1 and mTORC2 in Group 3 was not as high as in Group 2, it was statistically significant (p

Hormonal and non-hormonal oral contraceptives given long-term to pubertal rats differently affect bone mass, quality and metabolism.

We investigated the effects of hormonal and non-hormonal oral contraceptives (OCs) on bone mass, mineralization, composition, mechanical properties, and metabolites in pubertal female SD rats. OCs were given for 3-, and 7 months at human equivalent doses. The combined hormonal contraceptive (CHC) was ethinyl estradiol and progestin, whereas the non-hormonal contraceptive (NHC) was ormeloxifene. MicroCT was used to assess bone microarchitecture and BMD. Bone formation and mineralization were assessed by static and dynamic histomorphometry. The 3-point bending test, nanoindentation, FTIR, and cyclic reference point indentation (cRPI) measured the changes in bone strength and material composition. Bone and serum metabolomes were studied to identify potential biomarkers of drug efficacy and safety and gain insight into the underlying mechanisms of action of the OCs. NHC increased bone mass in the femur metaphysis after 3 months, but the gain was lost after 7 months. After 7 months, both OCs decreased bone mass and deteriorated trabecular microarchitecture in the femur metaphysis and lumbar spine. Also, both OCs decreased the mineral: matrix ratio and increased the unmineralized matrix after 7 months. After 3 months, the OCs increased carbonate: phosphate and carbonate: amide I ratios, indicating a disordered hydroxyapatite crystal structure susceptible to resorption, but these changes mostly reversed after 7 months, indicating that the early changes contributed to demineralization at the later time. In the femur 3-point bending test, CHC reduced energy storage, resilience, and ultimate stress, indicating increased susceptibility to micro-damage and fracture, while NHC only decreased energy storage. In the cyclic loading test, both OCs decreased creep indentation distance, but CHC increased the average unloading slope, implying decreased microdamage risk and improved deformation resistance by the OCs. Thus, reduced bone mineralization by the OCs appears to affect bone mechanical properties under static loading, but not its cyclic loading ability. When compared to an age-matched control, after 7 months, CHC affected 24 metabolic pathways in bone and 9 in serum, whereas NHC altered 17 in bone and none in serum. 6 metabolites were common between the serum and bone of CHC rats, suggesting their potential as biomarkers of bone health in women taking CHC. Both OCs have adverse effects on various skeletal parameters, with CHC having a greater negative impact on bone strength.

Effects of Metformin and Preparations With Pleiotropic Effects on Testicular Biochemical Indices of Rats With Juvenile-Onset Metabolic Syndrome

Background. Metabolic syndrome (MS) is a complex of disorders characterized by abdominal obesity, insulin resistance and glucose tolerance, arterial hypertension, and all types of metabolic disorders. Taking into account the wide range of symptoms accompanying MS, the use of preparations with pleiotropic effects on metabolic processes in the body could be promising for its treatment.&#x0D; Objective. The aim of this study is comparative estimation of metformin or its combination with vitamins' complex or liposomal preparation treatment effects on DNA, RNA, histones, ATP, ADP, AMP contents, and DNA fragmentation processes in testes of rats with MS induced in juvenile age.&#x0D; Methods. MS model was induced by full replacement of drinking water with 10% fructose solution in Wistar male rats of 21–23 days age (50–70 g). DNA, RNA, histones, ATP, ADP, AMP contents, and DNA fragmentation processes investigations were carried out after 60 days of MS modeling and metformin or its combination with vitamins' complex or liposomal preparation treatment.&#x0D; Results. In experiments with pubertal rats with MS and metformin or its combination vitamins' complex or liposomal preparation treatment, we established partially corrective effects of these medications for DNA, RNA, histones, ATP, ADP, AMP contents, and DNA fragmentation processes changes caused by MS development.&#x0D; Conclusions. A comparative analysis of the studied preparations' effects under MS simulation in the juvenile age showed that none of these drugs was able to completely normalize the disorders in studied indicators caused by MS. However, both combinations of metformin with vitamins' complex or liposomal preparation were still more effective in these negative changes' correction then metformin itself. Metformin with vitamins' complex caused a more pronounced influence on the processes of DNA fragmentation, the levels of adenyl nucleotides, and the energy charge of rat testicular cells, while the corrective effect of metformin with liposomal preparation was more noticeable with respect to the content of chromatin components.

Leydig cell development in pubertal male rats is blocked by perfluorotetradecanoic acid through decreasing AMPK-mTOR-autophagy pathway

Perfluorotetradecanoic acid (PFTeDA) is a type of perfluoroalkyl acid that has been linked to various health effects in animals and humans. The study aimed to investigate the potential impact of PFTeDA exposure on Leydig cell development in rats during puberty. Understanding the effects of PFTeDA on Leydig cells is crucial as these cells play a significant role in male reproductive function. Male Sprague-Dawley rats were gavaged with PFTeDA at doses of 0, 1, 5, and 10 mg/kg/day from postnatal day 35–56. The serum hormone levels were measured and testicular transcriptome changes were analyzed by RNA-seq and verified by qPCR, and the levels of steroidogenesis-related proteins and energy regulators were measured. PFTeDA significantly reduced serum testosterone levels while slightly increasing LH levels. RNA-seq and qPCR analysis showed that genes responsive to oxidative phosphorylation (Naufa1 and Ndufs6) and steroidogenesis (Ldlr, Star, Cyp11a1) were markedly downregulated at ≥ 5 mg/kg, while those related to ferroptosis (Alox15) and cell senescence (Map2k3 and RT1-CE3) were significantly upregulated. PFTeDA markedly reduced SIRT1 (silent information regulator 1) /PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1α) and AMPKA (AMP activated kinase A), LC3B and Beclin1 (biomarkers for autophagy) levels while increasing phosphorylated mTOR. In vitro treatment of PFTeDA at 5 μM significantly reduced androgen output of Leydig cells from 35-day-old male rats while ferrostatin 1 (10 μM) reversed PFTeDA-mediated inhibition. In conclusion, the inhibitory effects of PFTeDA on pubertal rat Leydig cell development are possibly regulated by inducing ferroptosis thereby downregulating SIRT1/AMPKA/ autophagy pathways, eventually resulting in reduced steroidogenesis.

METABOLIC DYSFUNCTIONS CAUSED BY EARLY FRUCTOSE INGESTION ARE PREVENTED IN CONCURRENTLY EXERCISED ADULT MALE RATS

This study evaluated whether fructose ingestion at adolescence programs the development ofmetabolic syndrome (MetS) in adult rats and whether moderate-intensity combined exercisecan attenuate fructose-induced MetS compounds. Pubertal rats were trained on a treadmill(55-65% VO 2max ), 3 times/week, 44 min/session, for one month. They were allocated into fourgroups: sedentary control (SC), trained control (TC), sedentary fructose (SF), and trainedfructose (TF). Groups F ingested 10% fructose. Food intake (AI) and body weight (BW) weremeasured weekly. At 60 and 120 days of age, metabolic parameters were evaluated. Fructoseintake mainly affected animals in adult life, and these changes were related to glucoseintolerance (p=0.001), periepididymal fat (p&amp;lt;0.03), and increase in total cholesterol (TC) (p&amp;lt;0.001), triglycerides (TAGs) (p&amp;lt;0.0001) and insulin (p&amp;lt;0.0001) levels. Early physicalexercise was able to decrease periepididymal (p&amp;lt;0.003) and retroperitoneal (p&amp;lt;0.0002)adipose tissue, TC levels (p&amp;lt;0.0001) and glucose tolerance (p=0.21). Rats that receivedcombined treatments during adolescence showed low glycemia (p=0.003) and insulinemia(p&amp;lt;0.0001) during the intraperitoneal glucose tolerance test (ipGTT). HOMA-IR (p=0.02) andTYG (p=0.0003) scores also improved in these rats. We conclude that early ingestion of 10%fructose was effective in programming adult rats to MetS, and simultaneous moderateexercise attenuated these aggressions, causing changes in glycemic homeostasis and lipidmetabolism.

Protective Role of Kelulut Honey against Toxicity Effects of Polystyrene Microplastics on Morphology, Hormones, and Sex Steroid Receptor Expression in the Uterus of Rats.

Microplastics (MPs) are an emerging global pollutant. Previous studies have revealed that chronic exposure to MPs can affect animal and human reproductive health, particularly by impairing the reproductive system's normal functions, which may increase the risk of infertility in both males and females. Kelulut honey (KH), an excellent source of antioxidants, has been used to counteract the disruptive effects of Polystyrene microplastics (PS-MPs) in the rat uterus. Thus, this study aimed to investigate the potential protective effects of Kelulut honey against PS-MPs-induced uterine toxicity in pubertal rats. Prepubertal female Sprague Dawley rats were divided into four groups (n = 8): (i) normal control group (NC: treated with deionized water), MPs-exposed group (M: exposed to PS-MPs at 2.5 mg/kg), (iii) Kelulut honey group (DM: pretreated with 1200 mg/kg of KH 30 minutes before they were administered with PS-MPs at 2.5 mg/kg), and (iv) Kelulut honey control group (DC: only treated with KH at 2.5 mg/kg). The rats were treated orally once daily for six consecutive weeks. Uterine abnormalities in PS-MPs-exposed rats were significantly improved after concurrent treatment with Kelulut honey. Morphology improvement was observed and luminal epithelial cells seemed thicker with more goblet cells, glandular cells had a more regular and circular shape, stromal cell increased in size, interstitial gaps between stromal cells expanded, and the myometrium layer was thicker. Kelulut honey treatment also effectively normalized the suppressive effect of PS-MPs on the expression and distribution of sex steroid receptors (ERα and ERβ), as well as the level of serum gonadotropin (LH and FSH) and sex steroid (estradiol and progesterone) hormones. Kelulut honey can protect the female reproductive system against the disruptive effects of PS-MPs. The phytochemical properties of Kelulut honey might be responsible for these beneficial benefits. However, future studies are warranted to identify the mechanisms involved.

Effects of noopept on ocular, pancreatic and renal histopathology in streptozotocin induced prepubertal diabetic rats

ABSTRACT Diabetes mellitus (DM) is a chronic disease at all ages including childhood and puberty. Failure to treat DM can cause retinopathy, nephropathy and neuropathy. Endocrine and metabolic changes during the pubertal period complicate management of DM. Noopept is a cognitive enhancer that exhibits antidiabetic properties. We investigated the effect of noopept on the histopathology of the cornea, retina, kidney and pancreas in pubertal diabetic rats. We allocated 60 prepubertal male rats randomly into six groups of 10: untreated control (C), DM control (DC), noopept control (NC), DM + noopept (D + N), DM + insulin (D + I) and DM + insulin + noopept (D + I + N). DM was induced by streptozotocin in the DC, D + N, D + I and D + I + N groups. Noopept was administered to the NC, D + N and D + I + N groups; insulin was administered to the D + I and D + I + N groups for 14 days. On day 18 of the experiment, animals were sacrificed and eyes, kidneys and pancreata were excised for histological investigation. Renal tubule diameter and corneal and retinal thickness were increased significantly in DC groups compared to the control group. The D + I, D + N and D + I + N groups exhibited fewer DM induced pathological changes than the DC group. The D + I + N group exhibited no significant differences in renal tubule diameter and corneal and retinal thickness compared to the DC group. Our findings suggest that noopept is protective against DM end organ complications in streptozotocin induced diabetic pubertal rats.

Mechanism of autophagy mediated by IGF-1 signaling pathway in the neurotoxicity of lead in pubertal rats

Lead can damage neuron synapses in the hippocampus and cause synaptic plasticity losses, and learning, memory, and intelligence impairments. Previous studies have focused on the functional and structural plasticity of hippocampal synapses; however, the specific molecular mechanisms behind such impairments are not fully understood. This study aimed to elucidate the molecular mechanisms of cognitive impairment in rats following chronic lead exposure and mitigate or prevent lead toxicity in the central nervous system. We found that lead exposure caused significant damage to rat nervous systems, that is, compared with the control group, the lead treatment group had more autophagosomes in their hippocampal neurons; lower serum and hippocampal IGF-1 levels; lower hippocampal IGF-1, IGF-1R, PI3K, Akt, and mTOR gene expression; and upregulated hippocampal autophagy-associated proteins levels. Brain stereotactic technology was used to conduct autophagy inhibitor in vivo intervention experiments, and the results of these experiments suggest that the autophagy inhibitor DC661 inhibited lead-exposure-induced autophagy and autophagy-related gene expression in the rat hippocampus, possibly through activation of the IGF-1 pathway. Overall, our findings suggest that lead might activate hippocampal autophagy through the IGF-1/PI3K/Akt/mTOR signaling pathway. Therefore, this study provides a novel molecular mechanism underlying developmental toxicity in pubertal rats induced by lead exposure and provides a new target for anticipation and reversal of such neurotoxicity.

Retraction: Nuclear Morphometric Analysis of Leydig Cells of Male Pubertal Rats Exposed In Utero to Di(n-butyl) Phthalate

[This retracts the article on p. 439 in vol. 26, PMID: 24526819.].

Endocrine adverse effects of mono(2-ethylhexyl) phthalate and monobutyl phthalate in male pubertal rats.

Considering that research of adverse effects of mono(2-ethylhexyl) phthalate (MEHP) and monobutyl phthalate (MBP), two key metabolites of the most common phthalates used as plasticisers in various daily-life products, has been scattered and limited, the aim of our study was to provide a more comprehensive analysis by focusing on major organ systems, including blood, liver, kidney, and pancreas in 66 male pubertal rats randomised into eleven groups of six. The animals were receiving either metabolite at doses of 25, 50, 100, 200, or 400 mg/kg bw a day by gavage for 28 days. The control group was receiving corn oil. At the end of the experiment, blood samples were collected for biochemical, haematological, and immunological analyses. Samples of kidney, liver, and pancreas were dissected for histopathological analyses. Exposure to either compound resulted in increased liver and decreased pancreas weight, especially at the highest doses. Exposed rats had increased ALT, AST, glucose, and triglyceride levels and decreased total protein and albumin levels. Both compounds increased MCV and decreased haemoglobin levels compared to control. Although they also lowered the insulin level, exposed rats had negative islet cell and insulin antibodies, same as control. Treatment-related histopathological changes included sinusoidal degeneration in the liver, glomerular degeneration in the kidney, and degeneration of pancreatic islets. Our findings document toxic outcomes of MEHP and MBP on endocrine organs in male pubertal rats but also suggest the need for additional studies to better understand the mechanisms behind adverse effects in chronic exposure.

A comparative assessment of artificial and natural energy drinks in the epididymal and testicular milieu

"Artificial and natural energy drinks are both taken for increased energy, physical stamina, and alertness, although they differ in composition. This study investigated the effects of artificial and natural energy drinks on the testicular milieu in male pubertal rats. Eighteen Wistar rats were randomly divided into 3 groups of 6 rats each and all animals had access to food ad libitum. Group 1: (control) received water only; Group 2: (artificial energy drink- AED) received AED; Group 3: (natural energy drink- NED) received NED. A dose of 1.41ml/day/150g animal was administered and this lasted for 28 days. Sperm and testicular variables, biochemical parameters, and hormonal assays were carried out. There were significant decreases in the levels of testosterone, Lactate dehydrogenase, glucose, 3β-Hydroxysteroid dehydrogenase, and 17β- Hydroxysteroid dehydrogenase activities in AED and NED groups when compared to the control group. There was a marked increment in sperm abnormalities in the NED group when compared to AED and control groups. Also, the intake of AED led to an elevated level of Glucose-6-phosphate dehydrogenase compared to the control while a significant reduction was observed in the NED group when compared to the AED group. Artificial and natural energy drinks although consumed for strength and vigor distorted epididymis and testicular integrity via alteration of the testicular metabolism, lowering sperm quality and androgenic hormones in pubertal male Wistar rats. Keywords: energy drink, jaggery, sperm quality, steroidogenic enzymes, lactate dehydrogenase."