Laboratory Animal Studies Research Articles

A Review of Human Exposure to Microplastics and Insights Into Microplastics as Obesogens.

The ubiquitous exposure of humans to microplastics (MPs) through inhalation of particles in air and ingestion in dust, water, and diet is well established. Humans are estimated to ingest tens of thousands to millions of MP particles annually, or on the order of several milligrams daily. Available information suggests that inhalation of indoor air and ingestion of drinking water bottled in plastic are the major sources of MP exposure. Little is known on the occurrence of MPs in human diet. Evidence is accumulating that feeding bottles and medical devices can contribute to MP exposure in newborns and infants. Biomonitoring studies of human stool, fetus, and placenta provide direct evidence of MP exposure in infants and children. MPs <20 µm were reported to cross biological membranes. Although plastics were once perceived as inert materials, MP exposure in laboratory animals is linked to various forms of inflammation, immunological response, endocrine disruption, alteration of lipid and energy metabolism, and other disorders. Whereas exposure to MPs itself is a concern, MPs can also be sources of exposure to plastic additives and other toxicants. Exposure of human cell lines to MP additives such as phthalates, bisphenols, and organotins causes adverse effects through the activation of nuclear receptors, peroxisome proliferator-activated receptors (PPARs) α, β, and γ, and retinoid X receptor (RXR), leading to oxidative stress, cytotoxicity, immunotoxicity, thyroid hormone disruption, and altered adipogenesis and energy production. The size, shape, chemical composition, surface charge, and hydrophobicity of MPs influence their toxicity. Maternal transfer of MPs to the developing fetus has been demonstrated in exposed laboratory animals and through the analysis of human placenta. In laboratory animal studies, maternal exposure to MPs altered energy and lipid metabolism in offspring and subsequent generations. Moreover, concomitant with the global increase in plastics production, the prevalence of overweight and obesity in human populations has increased over the past five decades, and there is evidence to support the hypothesis that MPs and their additives are potential obesogens. Even though MP exposures are ubiquitous and toxic effects from such exposures are a concern, systematic studies on this topic remain urgently needed.

Neurophysiological correlate of incubation of craving in individuals with methamphetamine use disorder.

Previous studies both in laboratory animals and humans have reported that abstinence induces incubation of cue-induced drug craving for nicotine, alcohol, cocaine, and methamphetamine. However, current experimental procedures utilized to study incubation of methamphetamine craving do not incorporate the temporal dynamics of neuropsychological measures and electrophysiological activities associated with this incubation process. This study utilized the high-density electroencephalogram (EEG) signals as a rapid, inexpensive, and noninvasive measure of cue-induced craving potential. A total of 156 male individuals with methamphetamine use disorder (MUD) enrolled in this multisite, cross-sectional study. Structured clinical interview data, self-report questionnaires (cued craving, quality of sleep, impulsivity, anxiety, and depression) and resting-state, eye-closed 128 high-density channel EEG signals were collected at 5 abstinence duration time points (<1, 1-3, 3-6, 6-12, and 12-24 months) to track the neuropsychological and neurophysiological signatures. Cue-induced craving was higher after 1-3 months than after the other time points. This incubation effect was also observed for sleep quality but not for anxiety, depression, and impulsivity symptoms, along with exhibited decreased power spectrum for theta (5.5-8 Hz) and alpha (8-13 Hz), and increased in beta (16.5-26.5 Hz) frequency band. Source reconstructed resting-state EEG analysis showed increased synchronization of medial prefrontal cortex (MPFC) for the beta frequency band in 1-3 months abstinent MUD group, and associated with the incubation of craving. Remarkably, the robust incubation-related abnormalities may be driven by beta-band source space connectivity between MPFC and bilateral orbital gyrus (ORB). Our findings suggest the enhancement of beta activity in the incubation period most likely originates from a dysfunction involving frontal brain regions. This neurophysiological signature of incubation of craving can be used to identify individuals who might be most susceptible to relapse, providing a potential insight into future therapeutic interventions for MUD via neuromodulation of beta activity.

LiftPose3D, a deep learning-based approach for transforming two-dimensional to three-dimensional poses in laboratory animals.

Markerless 3D pose estimation has become an indispensable tool for kinematic studies of laboratory animals. Most current methods recover 3D pose by multi-view triangulation of deep network-based 2D pose estimates. However, triangulation requires multiple, synchronized cameras and elaborate calibration protocols that hinder its widespread adoption in laboratory studies. Here we describe LiftPose3D, a deep network-based method that overcomes these barriers by reconstructing 3D poses from a single 2D camera view. We illustrate LiftPose3D’s versatility by applying it to multiple experimental systems using flies, mice, rats, and macaque monkeys and in circumstances where 3D triangulation is impractical or impossible. Our framework achieves accurate lifting for stereotyped and non-stereotyped behaviors from different camera angles. Thus, LiftPose3D permits high-quality 3D pose estimation in the absence of complex camera arrays, tedious calibration procedures, and despite occluded body parts in freely behaving animals.

Implications of the use of Strontium Ranelate (SRAN) in periodontics, dental implantology, oral surgery, orthodontics and endodontics and its possibility of application as storage media for avulsed teeth

Dental avulsion is still public health problem and tooth replantation has important unsuccess rates due to root resorption. Strontium ranelate (SRAN) presents antiresorptive property on the bone tissue and stimulates bone formation. So we aimed to comprehensively review the literature to 1- understand the mechanism of action of SRAN regarding to its propaedeutic in periodontics, dental implantology, oral surgery, orthodontics and endodontics, 2- present the current scientific knowledge about the SRAN efficiency on tooth avulsion; 3- observe fails and gaps in the literature and open up for unexplored ideas for SRAN uses and applications. An electronic search was performed crossing the key words ‘strontium ranelate’, ‘periodontics’, ‘dental implantology’, ‘oral surgery’, ‘orthodontics’ and ‘endodontics’, PubMed/Medline, Lilacs and BBO electronic databases were searched for research articles, reviews of literature, animal laboratory studies and laboratory studies, which had been published in English until July 2020. Twenty-five articles fulfilled the inclusion and exclusion criteria. The available literature demonstrates that SRAN provides a really better propaedeutic on the bone tissue and that the topical applications show a lower risk of side effects. That open up new perspectives and for the use of SRAN as a potential storage media for avulsed teeth.

When Is Temporary Threshold Shift Injurious to Marine Mammals?

Evidence for synaptopathy, the acute loss of afferent auditory nerve terminals, and degeneration of spiral ganglion cells associated with temporary threshold shift (TTS) in traditional laboratory animal models (e.g., mice, guinea pigs) has brought into question whether TTS should be considered a non-injurious form of noise impact in marine mammals. Laboratory animal studies also demonstrate that both neuropathic and non-neuropathic forms of TTS exist, with synaptopathy and neural degeneration beginning over a narrow range of noise exposures differing by ~6–9 dB, all of which result in significant TTS. Most TTS studies in marine mammals characterize TTS within minutes of noise exposure cessation, and TTS generally does not achieve the levels measured in neuropathic laboratory animals, which have had initial TTS measurements made 6–24 h post-exposure. Given the recovery of the ear following the cessation of noise exposure, it seems unlikely that the magnitude of nearly all shifts studied in marine mammals to date would be sufficient to induce neuropathy. Although no empirical evidence in marine mammals exists to support this proposition, the regulatory application of impact thresholds based on the onset of TTS (6 dB) is certain to capture the onset of recoverable fatigue without tissue destruction.

Oxygen Toxicity in Critically Ill Adults.

Oxygen supplementation is one of the most common interventions in critically ill patients. Despite over a century of data suggesting both beneficial and detrimental effects of supplemental oxygen, optimal arterial oxygenation targets in adult patients remain unclear. Laboratory animal studies have consistently showed that exposure to a high FiO2 causes respiratory failure and early death. Human autopsy studies from the 1960s purported to provide histologic evidence of pulmonary oxygen toxicity in the form of diffuse alveolar damage. However, concomitant ventilator-induced lung injury and/or other causes of acute lung injury may explain these findings. Although some observational studies in general populations of critically adults showed higher mortality in association with higher oxygen exposures, this finding has not been consistent. For some specific populations, such as those with cardiac arrest, studies have suggested harm from targeting supraphysiologic PaO2 levels. More recently, randomized clinical trials of arterial oxygenation targets in narrower physiologic ranges were conducted in critically ill adult patients. Although two smaller trials came to opposite conclusions, the two largest of these trials showed no differences in clinical outcomes in study groups that received conservative versus liberal oxygen targets, suggesting that either strategy is reasonable. It is possible that some strategies are of benefit in some subpopulations, and this remains an important ongoing area of research. Because of the ubiquity of oxygen supplementation in critically ill adults, even small treatment effects could have a large impact on a global scale.

Лечебная коррекция ишемических повреждений головного мозга у брахицефалических пород собак

The article presents data on the features of cerebral circulation disorders in dogs of brachycephalic breeds. The anatomical breed prerequisites that overload the small circulatory system and, as a result, increase the state of hypoxia are listed. Data from neurological examinations and laboratory studies of such animals are presented. The effectiveness and expediency of using the drug Mexidol-Vet® in animals of this group have been proved. Recommendations for taking the drug to prevent relapses are given.

Методи оцінки нейротоксичного впливу хімічних речовин на розвиток організму в пре- і постнатальному періодах

Aim of the research. Analysis of approaches to the assessment of neurotoxic effects of chemicals during ontogenesis. The dangerous tendency of the increase in the incidence of pathology of the nervous system in the child and the mother, who during pregnancy was exposed to neurotoxicants, necessitates the protection of the child’s body from such a negative effect of chemicals. One of the possible preventive ways to solve this problem is screening of xenobiotics before their widespread application, as well as identification of their ability to cause neurotoxic effects on the body during its development, and banning substances, neurotoxic effects of which on the development of progeny are proven. Materials and Methods. Detection of adverse effects at the stage of foetal development and then at the beginning of the functioning of a nervous system in the postnatal period requires complex experimental studies in laboratory animals, which are described in the recommendations of OECD guideline 426 (OECD Guideline for Testing of Chemicals; Guideline 426: Developmental Neurotoxicity Study, 2007). The OECD guideline 426 protocol provides for a wide range of methods for assessing sensory, motor, behavioural and cognitive functions. Conclusions. Analysis of data given in publications and methodological approaches to research and evaluation of neurotoxic effects of chemicals on the developing organism showed that to obtain representative results it is important to take into account all factors that may affect the result, select adequate informative tests and comply with all requirements. In Ukraine, international methodological approaches to the study of neurotoxic effects of pesticides on the body at the stage of development in the process of ontogenesis are applied at the L.I. Medved’s Research Center of Preventive Toxicology, Food and Chemical Safety, Ministry of Health, Ukraine (State Enterprise), Kyiv, Ukraine. Key Words: nervous system, neurotoxic effects, OECD guideline 426, neurobehavioral tests.

Responding Fails to Extinguish During Human-Laboratory Experiments of Resurgence

Resurgence is observed when a previously extinguished behavior reemerges while a more recently reinforced behavior is extinguished. Resurgence is further defined as responding that is greater than an inactive control response that has never produced reinforcement. Recent studies of resurgence using neurotypical adults as participants in human-laboratory investigations have produced discrepant patterns of responding compared to nonhuman animal laboratory studies when comparing control response performance. Namely, human-laboratory investigations have produced no differences between target and control responding, and persistence of all response types across the resurgence-test phase. In the present study, we conducted two human-laboratory experiments to determine if these effects were a product of the history of reinforcement associated with the target response as well as the types of technology used in human-laboratory studies. For all participants, we found no differences in levels of resurgence and occurrence for the target and control response, respectively. Moreover, we observed persistence of all response types across the resurgence-test phase in a manner consistent with prior research. This finding was apparent even when the length of baseline (i.e., reinforcement for the target) was increased, when the length of extinction was increased, and when low-technology stimuli were used. We highlight the implications of this outcome in the context of recent human-laboratory studies that have used arbitrary responses to study resurgence, and discuss the possible role of verbal mediation in these investigations.

Daily Lifestyle Modifications to Improve Quality of Life and Survival in Glioblastoma: A Review.

Survival in glioblastoma remains poor despite advancements in standard-of-care treatment. Some patients wish to take a more active role in their cancer treatment by adopting daily lifestyle changes to improve their quality of life or overall survival. We review the available literature through PubMed and Google Scholar to identify laboratory animal studies, human studies, and ongoing clinical trials. We discuss which health habits patients adopt and which have the most promise in glioblastoma. While results of clinical trials available on these topics are limited, dietary restrictions, exercise, use of supplements and cannabis, and smoking cessation all show some benefit in the comprehensive treatment of glioblastoma. Marital status also has an impact on survival. Further clinical trials combining standard treatments with lifestyle modifications are necessary to quantify their survival advantages.

Diet and gut microbiome enterotype are associated at the population level in African buffalo

Studies in humans and laboratory animals link stable gut microbiome “enterotypes” with long-term diet and host health. Understanding how this paradigm manifests in wild herbivores could provide a mechanistic explanation of the relationships between microbiome dynamics, changes in dietary resources, and outcomes for host health. We identify two putative enterotypes in the African buffalo gut microbiome. The enterotype prevalent under resource-abundant dietary regimes, regardless of environmental conditions, has high richness, low between- and within-host beta diversity, and enrichment of genus Ruminococcaceae-UCG-005. The second enterotype, prevalent under restricted dietary conditions, has reduced richness, elevated beta diversity, and enrichment of genus Solibacillus. Population-level gamma diversity is maintained during resource restriction by increased beta diversity between individuals, suggesting a mechanism for population-level microbiome resilience. We identify three pathogens associated with microbiome variation depending on host diet, indicating that nutritional background may impact microbiome-pathogen dynamics. Overall, this study reveals diet-driven enterotype plasticity, illustrates ecological processes that maintain microbiome diversity, and identifies potential associations between diet, enterotype, and disease.

Acute and Subacute Toxicity Assessment of Ethyl Acetate Extracts from Aerial Parts of Clerodendrum thomsoniae Balf.f in Rodents

Clerodendrum is a genus of about 500 species belongs to the family Lamiaceae. Several species of this genus have been proved for the treatment of various diseases. Clerodendrum thomsoniae Balf.f were selected in this study; according to the literature available, there is no systematic toxicity studies for this plant were described. The current study was therefore carried out to evaluate the acute and sub-acute toxicity in mice and rats. The acute oral toxicity study was performed in mice following OECD guidelines 425, and the sub-acute toxicity was performed in male and female rats following OECD guidelines 407. The results showed that mice given a single dose of up to 2000 mg/kg orally did not show any toxicity signs or mortality. In the sub-acute toxicity analysis in rats, 3 specific daily doses of 150, 300, and 600 mg/kg for 28 days did not induce any major changes to the hematological and biochemical parameters. Histopathological studies revealed normal architecture that did not indicate any morphological disturbances. In our study, no deaths or any signs of toxicity were found in acute and subacute toxicity studies after oral administration according to OECD guidelines, which concluded that ethyl acetate extract of Clerodendrum thomsoniae Balf (EACT) could use for in vivo biological activity studies in laboratory animals to explore its various medicinal activity before study in human subjects.

Effects of Low-level Laser Therapy on Fibroblast Density in Achilles Tendon Rupture Healing

Objective: To investigate the effect of low-level laser therapy (LLLT) on fibroblast proliferation as a part of the tendon healing cascade. Methods: This was an unpaired comparative experimental animal laboratory study with one control groups and two experimental groups, each consisted of 10 Sprague Dawley rats. The experimental groups 1 and 2 were given infrared irradiation for 15 minutes and 30 minutes per day, respectively, after having their achilles tendon partially cut. Histological assessment was carried out to assess the fibroblast density in healing site after three weeks on intervention. Results: The median values of fibroblast density in group 1, group 2, and control group were 1, 2, and 1, respectively, with a p-value of 0.014. No significant difference (p = 0.123) was identified on Mann-Whitney test between the fibroblast density of group 1 and group 2. The same was also true forgroup 1 and control group (p = 0.315). A significant difference was found between group 2 and control group (p = 0.005). Conclusions: A regime of LLLT irradiation of 30 min/day for two weeks (1080 J cm-2) improves the fibroblast proliferation amidst tendon healing in a partially injured achilles tendon in a rat model, which is not seen in the regime with a 15 min/day duration. This emphasizes the significance of irradiation time to improve tendon healing, despite the deficient understanding of the mechanism.

The Paradoxical Roles of Orphan Nuclear Receptor 4A (NR4A) in Cancer

The three-orphan nuclear receptor 4A genes are induced by diverse stressors and stimuli, and there is increasing evidence that NR4A1 (Nur77), NR4A2 (Nurr1), and NR4A3 (Nor1) play an important role in maintaining cellular homeostasis and in pathophysiology. In blood-derived tumors (leukemias and lymphomas), NR4A expression is low and NR4A1-/-/NR4A3-/- double knockout mice rapidly develop acute myelocytic leukemia, suggesting that these receptors exhibit tumor suppressor activity. Treatment of leukemia and most lymphoma cells with drugs that induce expression of NR4A1and NR4A3 enhances apoptosis, and this represents a potential clinical application for treating this disease. In contrast, most solid tumor-derived cell lines express high levels of NR4A1 and NR4A2, and both receptors exhibit pro-oncogenic activities in solid tumors, whereas NR4A3 exhibits tumor-specific activities. Initial studies with retinoids and apoptosis-inducing agents demonstrated that their cytotoxic activity is NR4A1 dependent and involved drug-induced nuclear export of NR4A1 and formation of a mitochondrial proapoptotic NR4A1-bcl-2 complex. Drug-induced nuclear export of NR4A1 has been reported for many agents/biologics and involves interactions with multiple mitochondrial and extramitochondrial factors to induce apoptosis. Synthetic ligands for NR4A1, NR4A2, and NR4A3 have been identified, and among these compounds, bis-indole derived (CDIM) NR4A1 ligands primarily act on nuclear NR4A1 to inhibit NR4A1-regulated pro-oncogenic pathways/genes and similar results have been observed for CDIMs that bind NR4A2. Based on results of laboratory animal studies development of NR4A inducers (blood-derived cancers) and NR4A1/NR4A2 antagonists (solid tumors) may be promising for cancer therapy and also for enhancing immune surveillance.

Mingjing granule, a traditional Chinese medicine in the treatment of neovascular age-related macular degeneration: study protocol for a randomized controlled trial

BackgroundNeovascular age-related macular degeneration (nAMD) is the most common cause of irreversible vision loss and blindness among the older people aged 50 and over. Although anti-vascular endothelial growth factor (anti-VEGF) therapies have resulted in improving patient outcomes, there are limitations associated with these treatments. In China, traditional Chinese medicine (TCM) has been used to treat eye diseases for more than 2000 years. Previous studies have shown that TCM may be beneficial for nAMD patients. However, explicit evidence has not been obtained. The purpose of the present trial is to examine the efficacy and safety of the Mingjing granule, a compound Chinese herbal medicine, for nAMD patients.Methods/designThis is a double-blind, placebo-controlled, randomized trial of Mingjing granule as an add-on to intravitreous ranibizumab for nAMD. One hundred eighty nAMD patients from six hospitals in China will be enrolled according to the inclusion and exclusion criteria and randomly allocated into two groups, 90 in each. All participants will receive a 24-week treatment and then be followed up for another 24 weeks. The primary outcome is the mean change of best-corrected visual acuity at week 24 and 48 as compared to the baseline. The secondary outcomes include mean change in central retinal thickness, area of retinal hemorrhage and exudation, and TCM syndrome score, mean number of intravitreal ranibizumab injection, and total cost of the treatment. Indexes of safety include blood regular test, urine regular test, liver function test, renal function test, and electrocardiogram from baseline to weeks 24 and 48. Qualitative control and some standard operating processes will be formed throughout the trial. Any ocular or systemic adverse events will be treated suitably, and related data will be recorded accurately and completely in the case report form.DiscussionBased on previous empirical and animal laboratory studies, this study will address the question of whether Mingjing granule could contribute to improving efficacy, safety, and efficiency with need for fewer intravitreal injections of anti-VEGF, improving compliance and visual outcomes in the management of persons with nAMD.Trial registrationChinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR2000035990. Registered on 21 August 2020.

Mechanisms of action of the erector spinae plane (ESP) block: a narrative review.

The erector spinae plane (ESP) block is an emerging regional anesthetic technique with significant potential for clinical benefit. Nevertheless, its exact mechanism(s) of action has been much debated. We reviewed the available literature to explore the possible mechanisms of analgesia for the ESP block. These include neural blockade and central inhibition from direct spread of local anesthetic to the paravertebral or epidural space; analgesia mediated by elevated local anesthetic plasma concentrations due to systemic absorption; immunomodulatory effects of local anesthetics; and an effect mediated through the mechanosensory properties of thoracolumbar fascia. Based on evidence from clinical, human cadaveric, animal, and mechanistic laboratory studies, the most probable primary mechanism is a direct effect of local anesthetic via physical spread and diffusion to neural structures in the fascial plane deep to the erector spinae muscles and adjacent tissue compartments. Biological plausibility of this primary mechanism is confirmed by injectate spread to the ventral rami of spinal nerves (though quite variable) in most studies. There is consistent involvement of dorsal rami; epidural spread is a less commonly observed phenomenon. A systemic effect of local anesthetic is also plausible, but unlikely to be a major contributor to clinical analgesic efficacy. The evidence for significant analgesia due to other proposed mechanisms, such as fascia-mediated analgesia or lymphatic spread, are currently limited and thus remain speculative. Understanding the mechanisms of action could assist clinicians in further investigating and refining ESP block performance, with the ultimate goal of optimizing analgesic efficacy and improving postoperative patient outcomes.

Imidacloprid as Reproductive Toxicant in Laboratory Animals: A Review

Imidacloprid is a neonicotinoid used worldwide in agriculture sector for controlling sucking insect pests. It has high specificity to insects and relatively low risk to non-targets including mammals. Chronic exposure to this insecticide is, however, toxic to mammalian systems. Biomagnification of residual effects in the food chain necessitates studies on their adverse effects. Hepatotoxic, neurotoxic, immunotoxic and genotoxic effects of imidacloprid intoxication are well known. The present review recapitulates knowledge about toxicity caused by imidacloprid to male and female reproductive systems based on studies in laboratory animals. Studies have revealed toxic effects of imidacloprid on parents as well as the offsprings. Reproductive toxicity of imidacloprid includes altered hormonal level, disturbance in estrous cyclicity, impaired fertility, spontaneous abortion, stillbirths and teratogenic defects. These changes are caused due to production of free radicals during metabolism which ultimately lead to oxidative stress and tissue damage.

Fundamentals of Nanocarriers and Probiotics in the Treatment of Cervical Cancer

Cancer is a pivotal disease, which is a serious concern towards scientific research. In the recent era of scientific discovery and innovation, probiotics have been proposed as a new preventive and therapeutic option in therapy and to control cancer growth. Probiotics may thus offer a new way in research to investigate active compounds in different probiotic strains having anticancer features. Studies in laboratory animals and cell lines with respect to cancer treatments are encouraging. With rare conventional treatments, the need for new alternatives as the transportation of chemotherapeutic agents by nanocarriers using nanotechnology is one such approach. This review considers various drug delivery systems used in the therapy of cervical cancer, such as dendrimers, liposomes and nanoparticles. These drug delivery systems assist in the improvement of pharmacological activity, solubility, bioavailability and, thus, facilitating new innovative therapeutic technologies. This review summarizes the application of nanotechnology and probiotics in the treatment of cervical cancer.

Continuous versus extended antipsychotic dosing in schizophrenia: Less is more

Antipsychotic drugs temper psychotic symptoms by interacting with dopamine D2 receptors to reduce dopamine neurotransmission. Currently, the standard of care involves antipsychotic treatment protocols that achieve steady-state levels of medication. Maintaining patients on continuous treatment is thought to be necessary to keep them stabilised. However, continuous antipsychotic exposure increases the risk of adverse effects over time. These effects include metabolic and cardiovascular disorders, extrapyramidal complications, and dopamine receptor supersensitivity, the latter of which could potentially promote both treatment tolerance and psychosis relapse. In the present review, we describe evidence showing that continuous exposure to antipsychotic drugs can not only worsen long-term outcome, but—past acute phase treatment—it is also unnecessary to effectively manage schizophrenia symptoms. We also describe evidence that regular but extended dosing, allowing predictable periods of lower antipsychotic levels/D2 occupancy, is both safe and effective in patients, and it greatly reduces drug exposure overall. Studies in laboratory animals show that compared to continuous antipsychotic exposure, regular but extended dosing actually has superior antipsychotic-like efficacy, and it also substantially reduces the likelihood of both motor side effects and dopamine receptor supersensitivity. We propose that regular, but extended dosing should be considered in the long-term treatment of people with schizophrenia, because the available evidence suggests it can be just as effective as continuous treatment, while decreasing overall drug exposure and potentially reducing harmful side effects.

Fetal and Postnatal Nicotine Exposure Modifies Maturation of Gonocytes to Spermatogonia in Mice.

Studies in laboratory animals have shown that male offspring from dams, exposed to nicotine during pregnancy and postnatal periods, show alterations in fertility, although the origin of this is still uncertain. In this study, we examined in a mouse model if the process of gonocyte maturation to spermatogonia was affected in male offspring from dams with nicotine administration during pregnancy and postnatal periods. BALB/C mice, with and without nicotine administrations in pregnancy and postnatal periods, were studied. The animals were euthanized at 3, 7, 10, 16, and 35 days postpartum (dpp). Testicular tissue samples were processed for histological, ultrastructural, and immunohistochemical studies; and testicular lipoperoxidation was determined. It was observed that in the nicotine-exposed animals, there was increased apoptosis and a reduction in the number of gonocytes that matured to spermatogonia. This gonocyte-spermatogonia maturation reduction was associated with a greater immunoreactivity to nicotinic acetylcholine receptors in the germ cells. Lipoperoxidation was similar in both groups until 16 dpp, with significant reduction at 35 dpp. Our findings suggest that nicotine intake during pregnancy and postnatal periods can affect the process of maturation of gonocytes to spermatogonia and the pool of available spermatogonia for spermatogenesis.