Targeting the purinergic pathway in breast cancer and its therapeutic applications.

Breast cancer (BC) is the most frequent cause of death among women, representing a global public health problem. Here, we aimed to discuss the correlation between the purinergic system and BC, recognizing therapeutic targets. For this, we analyzed the interaction of extracellular nucleotides and nucleosides with the purinergic receptors P1 and P2, as well as the influence of ectonucleotidase enzymes (CD39 and CD73) on tumor progression. A comprehensive bibliographic search was carried out. The relevant articles for this review were found in the PubMed, Scielo, Lilacs, and ScienceDirect databases. It was observed that among the P1 receptors, the A1, A2A, and A2B receptors are involved in the proliferation and invasion of BC, while the A3 receptor is related to the inhibition of tumor growth. Among the P2 receptors, the P2X7 has a dual function. When activated for a short time, it promotes metastasis, but when activated for long periods, it is related to BC cell death. P2Y2 and P2Y6 receptors are related to BC proliferation and invasiveness. Also, the high expression of CD39 and CD73 in BC is strongly related to a worse prognosis. The receptors and ectonucleotidases involved with BC become possible therapeutic targets. Several purinergic pathways have been found to be involved in BC cell survival and progression. In this review, in addition to analyzing the pathways involved, we reviewed the therapeutic interventions already studied for BC related to the purinergic system, as well as to other possible therapeutic targets.

Influence of biosafety materials of the laser output power.

Biosafety materials used in the correct handling of low power laser equipment may interfere on the power delivered at the target tissue and, possibly, on the effects on biological tissues. The aim of this study was to evaluate the interference of the use of polyvinyl chloride (PVC) and polyethylene (PEAD) protection materials on the output power of low power lasers. Two low power diode laser devices with different wavelengths (red and infrared) were used. For each wavelength, two protection materials and two evaluation times (before and after protection) were considered. The output power (mW) was measured with the tip positioned in close contact with the power meter receiver. Parametric statistical test, two-way ANOVA for repeated measures (protection material and time), was performed considering the level of significance of 5%. In respect to "time", all groups had the output power reduced after placing the protective material (p < 0.05). Comparing the protection materials, the PEAD showed a greater reduction in output power than the PVC for both red and infrared wavelengths. It was concluded that, among the biosafety materials tested, PVC is the most suitable for the protection of the tip of the low power lasers.

IAEA contribution to the development of 64Cu radiopharmaceuticals for theranostic applications.

Copper-64 is a very attractive radioisotope with unique nuclear properties that allow using it as both a diagnostic and therapeutic agent, thus providing an almost ideal example of a theranostic radionuclide. A characteristic of Cu-64 stems from the intrinsic biological nature of copper ions that play a fundamental role in a large number of cellular processes. Cu-64 is a radionuclide that reflects the natural biochemical pathways of Cu-64 ions, therefore, can be exploited for the detection and therapy of certain malignancies and metabolic diseases. Beside these applications of Cu-64 ions, this radionuclide can be also used for radiolabelling bifunctional chelators carrying a variety of pharmacophores for targeting different biological substrates. These include peptide-based substrates and immunoconjugates as well as small-molecule bioactive moieties. Fueled by the growing interest of Member States (MS) belonging to the International Atomic Energy Agency (IAEA) community, a dedicated Coordinated Research Project (CRP) was initiated in 2016, which recruited thirteen participating MS from four continents. Research activities and collaborations between the participating countries allowed for collection of an impressive series of results, particularly on the production, preclinical evaluation and, in a few cases, clinical evaluation of various 64Cu-radiopharmaceuticals that may have potential impact on future development of the field. Since this CRP was finalized at the beginning of 2020, this short review summarizes outcomes, outputs and results of this project with the purpose to propagate to other MS and to the whole scientific community, some of the most recent achievements on this novel class of theranostic 64Cu-pharmaceuticals.

Trophic dynamics (Dissolved Inorganic Nitrogen-DIN and Dissolved Inorganic Phosphorus-DIP) in tropical urban estuarine systems during periods of high and low river discharge rates.

This paper focused on the use of the biogeochemical LOICZ (Land Ocean Interactions in the Coastal Zone) to investigate the dynamics of DIN and DIP nutrients among three highly urbanized tropical estuaries (Barra das Jangadas (BJ), Recife (RE) and Timbó (TB)), located in the northeastern region of Brazil. The input data were obtained through in situ measurements (2007) and governmental agency databases (2001-2007). The balances of the non-conservative elements showed that the RE and TB systems alternated between sources and sinks during the observation periods (0.2-0.8 mmoles DIP m-2 d-1 and 0.1-10 mmoles DIN m-2 d-1). The metabolism rates in the systems indicated that the BJ system was autotrophic during the two observation periods (10-26 mmoles C m-2 d-1), while the RE system was heterotrophic (9-12 mmoles C m-2 d-1). The river discharge rates observed during the period 2001-2007 showed averages ranging from 9.4±3.8 to 18.4±7.7 m3s-1. Measurements of the trophic status in the RE system during 2007 characterized the system as eutrophic, thereby demonstrating high levels of chlorophyll-a and inorganic nutrients. The applications of balance sheets modeling proved to be very useful toward understanding the dynamics of estuarine systems dominated by large urban centers.

Environmental obesogen tributyltin chloride leads to abnormal hypothalamic-pituitary-gonadal axis function by disruption in kisspeptin/leptin signaling in female rats.

Tributyltin chloride (TBT) is a xenobiotic used as a biocide in antifouling paints that has been demonstrated to induce endocrine-disrupting effects, such as obesity and reproductive abnormalities. An integrative metabolic control in the hypothalamus-pituitary-gonadal (HPG) axis was exerted by leptin. However, studies that have investigated the obesogenic TBT effects on the HPG axis are especially rare. We investigated whether metabolic disorders as a result of TBT are correlated with abnormal hypothalamus-pituitary-gonadal (HPG) axis function, as well as kisspeptin (Kiss) action. Female Wistar rats were administered vehicle and TBT (100ng/kg/day) for 15days via gavage. We analyzed their effects on the tin serum and ovary accumulation (as biomarker of TBT exposure), estrous cyclicity, surge LH levels, GnRH expression, Kiss action, fertility, testosterone levels, ovarian apoptosis, uterine inflammation, fibrosis, estrogen negative feedback, body weight gain, insulin, leptin, adiponectin levels, as well as the glucose tolerance (GTT) and insulin sensitivity tests (IST). TBT led to increased serum and ovary tin levels, irregular estrous cyclicity, and decreased surge LH levels, GnRH expression and Kiss responsiveness. A strong negative correlation between the serum and ovary tin levels with lower Kiss responsiveness and GnRH mRNA expression was observed in TBT rats. An increase in the testosterone levels, ovarian and uterine fibrosis, ovarian apoptosis, and uterine inflammation and a decrease in fertility and estrogen negative feedback were demonstrated in the TBT rats. We also identified an increase in the body weight gain and abnormal GTT and IST tests, which were associated with hyperinsulinemia, hyperleptinemia and hypoadiponectinemia, in the TBT rats. TBT disrupted proper functioning of the HPG axis as a result of abnormal Kiss action. The metabolic dysfunctions co-occur with the HPG axis abnormalities. Hyperleptinemia as a result of obesity induced by TBT may be associated with abnormal HPG function. A strong negative correlation between the hyperleptinemia and lower Kiss responsiveness was observed in the TBT rats. These findings provide evidence that TBT leads to toxic effects direct on the HPG axis and/or indirectly by abnormal metabolic regulation of the HPG axis.

Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats.

Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposure increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration-response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT1 receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O2(-) production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease.

Effects of meteo-oceanographic conditions on the weathering processes of oil spills in northeastern Brazil.

This paper presents the graphical results of the Lagrangian-model and the weathering processes associated with oil spills in the tropical South Atlantic, taking into account the meteorological and oceanographic conditions of the study region. The scenarios were created in the Brazilian-NE waters adjacent, with simulation times of 670 h, and densities of 35, 25, and 15API with volume of 1590 m3 were considered. The main results showed that the meteo-oceanographic characteristics of the study region influence the trajectories and weathering processes in the oil spill. The trajectories varied for each launch point and reached the continent severely in January and October. The associated weathering processes showed higher rates in September and lower rates in April, indicative of the influence of phenomena such as Intertropical Tropical Convergence Zone and warm pool in the South Atlantic region. Sea surface temperature and wind speed are key factors that correlate positively with these months.

Pancreatic metastasis from osteosarcoma and Ewing sarcoma: literature review.

OBJECTIVES: Pancreatic metastasis from osteosarcoma and Ewing sarcoma is extremely rare. Differential diagnosis with primary pancreatic carcinoma is crucial before any treatment, but may be very difficult. MATERIAL AND METHODS: We searched for and reviewed the cases reported in the English literature. RESULTS: Twelve cases were identified, including nine osteosarcoma patients and three Ewing sarcoma cases. The median time between the sarcoma diagnosis and that of pancreatic metastasis was 3 years. In most of the cases, the pancreatic relapse followed or was associated with relapse(s) in one or more sites. Two out of eight patients with available follow-up were alive without disease 6+ and 11+ months after complete surgical removal, whereas five patients died from disease. Histological diagnosis was obtained before surgery in only five cases using percutaneous Tru-Cut biopsy in three cases and endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) in the two most recent ones. CONCLUSIONS: Osteosarcoma or Ewing sarcoma metastasis should be included in the differential diagnosis of pancreatic solid lesion, particularly in patients with a primary tumor. In this context, EUS and EUS-FNAB are reliable methods for the pre-operative diagnosis and should thus be discussed before any therapeutic decision.

Idealized hydrodynamical numerical model dataset with no-river runoff at the western tropical North Atlantic.

The western tropical North Atlantic (WTNA) is a very complex region, with the influence of intense western boundary currents in connection with equatorial zonal currents, important atmospheric forcings (e.g Intertropical Convergence Zone), mesoscale activities (e.g NBC rings), and the world's largest river discharge as the Amazon River runoff. The volume discharge is equivalent to more than one-third of the Atlantic river freshwater input, with a plume that spreads over the region reaching the northwestward Caribbean Sea and eastward longitudes of 30°W, and influencing from physical to biological structures. Therefore, in order to enable and encourage more understanding of the region, here we present a dataset based on an idealized scenario of no river runoff of the Amazon River and Par ´a River in the WTNA. The numerical simulations were conducted with a regional oceanic modeling system (ROMS) model and three pairs of files were generated with the model outputs: (i) ROMS-files, with the parameters of the ROMS-outputs raw data in a NetCDF format and monthly and weekly frequencies; (ii) MATLAB-files, which contain oceanographic parameters also in monthly and weekly frequencies; and (iii) NetCDF-files, with oceanographic parameters again in monthly and weekly frequencies. For each file, we present the coordinates and variable names, descriptions, and correspondent units. The dataset is available in the Science Data Bank repository (doi: https://doi.org/10.57760/sciencedb.02145).

Hunting for Genes Underlying Emotionality in the Laboratory Rat: Maps, Tools and Traps.

Scientists have systematically investigated the hereditary bases of behaviors since the 19th century, moved by either evolutionary questions or clinically-motivated purposes. The pioneer studies on the genetic selection of laboratory animals had already indicated, one hundred years ago, the immense complexity of analyzing behaviors that were influenced by a large number of small-effect genes and an incalculable amount of environmental factors. Merging Mendelian, quantitative and molecular approaches in the 1990s made it possible to map specific rodent behaviors to known chromosome regions. From that point on, Quantitative Trait Locus (QTL) analyses coupled with behavioral and molecular techniques, which involved in vivo isolation of relevant blocks of genes, opened new avenues for gene mapping and characterization. This review examines the QTL strategy applied to the behavioral study of emotionality, with a focus on the laboratory rat. We discuss the challenges, advances and limitations of the search for Quantitative Trait Genes (QTG) playing a role in regulating emotionality. For the past 25 years, we have marched the long journey from emotionality-related behaviors to genes. In this context, our experiences are used to illustrate why and how one should move forward in the molecular understanding of complex psychiatric illnesses. The promise of exploring genetic links between immunological and emotional responses are also discussed. New strategies based on humans, rodents and other animals (such as zebrafish) are also acknowledged, as they are likely to allow substantial progress to be made in the near future.

Retinol Levels and Severity of Patients with COVID-19.

The new coronavirus infection represents a serious threat to global health and economies. In this sense, it is paramount to know the nutritional factors that may be related to the prognosis of the disease. Evidence shows that vitamin A may play an important preventive and therapeutic role in supporting respiratory infections as in COVID-19. The aim of our study was to evaluate the association of vitamin A (retinol) status with the prognosis of the disease. A case-control study from a cohort study was conducted in Brazil between May and October 2020. The study population was chosen by convenience, consisting of participants diagnosed with COVID-19. Recruitment was carried out using different approaches, including through dissemination on social media and in four hospitals in the city of Natal/RN, Brazil, recruiting participants from the COVID-19 ward and hospitalized participants who tested positive for the disease. The participants were allocated into two groups according to severity, with a group of mild (n = 88) or critical (n = 106) patients and compared to a control group (selected before the pandemic, n = 46). The extraction of retinol serum was performed and analyzed using the high-performance liquid chromatography method (HPLC). The retinol level was calculated in mmol/L, and levels below 0.7 µmol/L (20 µg/dL) were considered to be a vitamin A deficiency. Our findings suggest that the participants with mild and critical COVID-19 had lower retinol levels compared to the healthy controls (p = 0.03). In addition, milder cases of COVID-19 were associated with increased symptoms and prolonged symptoms after 90 days since the beginning of infection. However, the survival analysis showed no association with higher cases of death among participants with vitamin A deficiency (p = 0.509). More studies are needed to understand how nutritional status, including vitamin A levels, can influence prognosis and is a risk factor for the development of long COVID syndrome.

Effectiveness of management zones for recovering parrotfish species within the largest coastal marine protected area in Brazil.

The establishment of multiple zones offering different protection levels within a Marine Protected Area (MPA) can minimize social conflicts while maintaining associated biodiversity benefits such as fish population replenishment. Parrotfishes are among one of the most ecologically important reef fishes; yet extremely overexploited worldwide. In this context, well-designed priority management areas allowing no fishing activity (no-take zones) could help recover fish species, such as parrotfishes, through a MPA zoning process. Here, we tested this hypothesis by identifying the spatial configuration of zones that maximize the recovery of endangered parrotfish species (Scarus trispinosus; Scarus zelindae; Sparisoma amplum; Sparisoma axillare; Sparisoma frondosum) at the largest MPA in Brazil protecting nearshore coral reefs (MPA Costa dos Corais). We used parrotfish distribution data to produce species distribution models (SDMs) and combined them with conservation planning tools to delineate priority zones following a systematic approach. Then, we contrasted priority zones against non-systematic, newly designed no-take zones based on managers' and stakeholders' perspectives. After mapping the predicted abundance of each species within both zones based upon field surveys, we found that priority zones were more effective than non-systematic ones for the protection of two out of the five species: Scarus trispinosus and Sparisoma amplum. Thus, we considered that designing systematic zones was particularly relevant for increased protection of the two parrotfish species facing the largest decline. The prioritization analyses also showed that priority areas for parrotfish conservation following a systematic approach were mostly located surrounding and within no-take zones delineated by local stakeholders. The spatial overlap between systematic and non-systematic zones was of 38%. Hence, our study reinforces the importance of considering scientific information and methods (e.g., spatial distribution data and prioritization analyses) as a complementary strategy along with local stakeholders' knowledge, for delineating and refining management zones within MPAs.

Telomeres: the role of shortening and senescence in major depressive disorder and its therapeutic implications.

Major depressive disorder (MDD) is one of the most prevalent and debilitating psychiatric disorders, with a large number of patients not showing an effective therapeutic response to available treatments. Several biopsychosocial factors, such as stress in childhood and throughout life, and factors related to biological aging, may increase the susceptibility to MDD development. Included in critical biological processes related to aging and underlying biological mechanisms associated with MDD is the shortening of telomeres and changes in telomerase activity. This comprehensive review discusses studies that assessed the length of telomeres or telomerase activity and function in peripheral blood cells and brain tissues of MDD individuals. Also, results from in vitro protocols and animal models of stress and depressive-like behaviors were included. We also expand our discussion to include the role of telomere biology as it relates to other relevant biological mechanisms, such as the hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, inflammation, genetics, and epigenetic changes. In the text and the discussion, conflicting results in the literature were observed, especially considering the size of telomeres in the central nervous system, on which there are different protocols with divergent results in the literature. Finally, the context of this review is considering cell signaling, transcription factors, and neurotransmission, which are involved in MDD and can be underlying to senescence, telomere shortening, and telomerase functions.

Anti-inflammatory Therapy by Cholinergic and Purinergic Modulation in Multiple Sclerosis Associated with SARS-CoV-2 Infection.

The virus "acute respiratory syndrome coronavirus 2" (SARS-CoV-2) is the etiologic agent of coronavirus disease 2019 (COVID-19), initially responsible for an outbreak of pneumonia in Wuhan, China, which, due to the high level of contagion and dissemination, has become a pandemic. The clinical picture varies from mild to critical cases; however, all of these signs already show neurological problems, from sensory loss to neurological diseases. Thus, patients with multiple sclerosis (MS) infected with the new coronavirus are more likely to develop severe conditions; in addition to worsening the disease, this is due to the high level of pro-inflammatory cytokines, which is closely associated with increased mortality both in COVID-19 and MS. This increase is uncontrolled and exaggerated, characterizing the cytokine storm, so a possible therapy for this neuronal inflammation is the modulation of the cholinergic anti-inflammatory pathway, since acetylcholine (ACh) acts to reduce pro-inflammatory cytokines and acts directly on the brain for being released by cholinergic neurons, as well as acting on other cells such as immune and blood cells. In addition, due to tissue damage, there is an exacerbated release of adenosine triphosphate (ATP), potentiating the inflammatory process and activating purinergic receptors which act directly on neuroinflammation and positively modulate the inflammatory cycle. Associated with this, in neurological pathologies, there is greater expression of P2X7 in the cells of the microglia, which positively activates the immune inflammatory response. Thus, the administration of blockers of this receptor can act in conjunction with the action of ACh in the anticholinergic inflammatory pathway. Finally, there will be a reduction in the cytokine storm and triggered hyperinflammation, as well as the level of mortality in patients with multiple sclerosis infected with SARS-CoV-2 and the development of possible neurological damage.

Green Tea Polyphenol Microparticles Based on the Oxidative Coupling of EGCG Inhibit Amyloid Aggregation/Cytotoxicity and Serve as a Platform for Drug Delivery.

The accumulation of cross-ß-sheet amyloid fibrils is a hallmark of all human amyloid diseases. The compound epigallocatechin-3-gallate (EGCG), the main polyphenol present in green tea, has been described to have beneficial effects in several pathologies, including amyloidogenic diseases. This polyphenol blocks amyloidogenesis and disaggregates a broad range of amyloidogenic peptides comprising amyloid fibrils in vitro. The mechanism by which EGCG acts in the context of amyloid aggregation is not clear. Most of the biological effects of EGCG are attributable to its antioxidant activity. However, EGCG-oxidized products appear to be sufficient for the majority of EGCG amyloid remodeling observed against some polypeptides. If controlled, EGCG oxidation can afford homogenous microparticles (MPs) and can serve as drug delivery agents. Herein, we produced EGCG MPs by oxidative coupling and analyzed their activity during the aggregation of the protein α-synuclein (α-syn), the main protein related to Parkinson's disease. The MPs modestly remodeled mature amyloid fibrils and efficiently inhibited the amyloidogenic aggregation of α-syn. The MPs showed low cytotoxicity against both dopaminergic cells and microglial cells. The MPs reduced the cytotoxic effects of α-syn oligomers. Interestingly, the MPs were loaded with another antiamyloidogenic compound, increasing their activity against amyloid aggregation. We propose the use of EGCG MPs as a bifunctional strategy, blocking amyloid aggregation directly and carrying a molecule that can act synergistically to alleviate the symptoms caused by the amyloidogenic pathway.

Disruption of fertility, placenta, pregnancy outcome, and multigenerational inheritance of hepatic steatosis by organotin exposure from contaminated seafood in rats.

Early life exposure to endocrine-disrupting chemicals (EDCs) is an emerging risk factor for development of complications later in life and in subsequent generations. We previously demonstrated that exposure to the EDC organotin (OT), which is present in contaminated seafood, resulted in reproductive abnormalities in female rats. However, few studies have explored the effect of OT accumulation in seafood on pregnancy outcomes. This led us to consider the potential effects of the OT present in seafood on fertility, pregnancy, the placenta, and the offspring. In this investigation, we assessed whether exposure to the OT in contaminated seafood resulted in abnormal fertility and pregnancy features and offspring complications. OT in contaminated seafood (LNI) was administered to female rats, and their fertility, pregnancy outcomes, and fetal liver morphology were assessed. LNI caused abnormal fertility, a reduction in the total number of pups, and an increase in serum testosterone levels compared to controls. Furthermore, LNI exposure caused irregular uterine morphology with inflammation and fibrosis and led to a reduction in embryonic implantation. In pregnant rats, LNI caused abnormal lipid profiles and livers with steatosis features. LNI exposure also causes placental morpho-physiology disruption, a high presence of glycogen and inflammatory cells, and irregular lipid profiles. In addition, LNI exposure caused an increase in large amounts of carbohydrate and lipid delivery to the fetus via an increase in placental nutrient sensor protein expressions (GLUT1, IRß/mTOR and Akt). In both genders of offspring, LNI exposure led to an increase in body weights, liver megakaryocytes, lipid accumulation, and oxidative stress (OS) levels. Collectively, these data suggest that OT exposure from contaminated seafood in female rats leads to reduced fertility, uterine implantation failure, pregnancy and placental metabolic outcome irregularities, offspring adiposity, liver steatosis, and an increase in OS. Furthermore, some of the effects of OT may be the result of obesogenic and multigenerational effects of OT in adult female rats.

High Power Laser and Photobiomodulation in Oral Surgery: Case Report.

Introduction: The labial frenum is a fold of mucous membrane that attaches the lip and the cheek to the alveolar mucosa, the gingiva, and the underlying periosteum. In some cases, its presence can cause a midline diastema, periodontal diseases related to food impaction, or retention of biofilm, among others. In such cases, lip frenectomy is indicated as treatment, which can be performed with a scalpel (conventional method), an electric scalpel, or a surgical laser. Objective: To show a clinical case performed at Laser Extension Project in Dentistry, Federal University of Maranhão grounded in a literature review. Case Presentation: A laser frenectomy was performed on a female patient, aged 20, who had a diastema between the upper central incisors and an indication for frenum removal. The high-power diode laser is excellent for procedures in soft tissue because its wavelength is well absorbed by hemoglobin and other pigments; its use also allows a reduction in the amount of anesthetic and medicines used. The parameters used were 2 W, in a continuous mode, 808 nm infrared emission; with delivery of the beam through optical fiber 300 µM; energy of 120 J; 20 pps. Conclusion: the high power diode laser allowed a satisfactory result, the procedure was safe, the technique was a simple one and of reduced clinical time, as mentioned in the literature. It is worth noting that the technique is dependent on the skill of the professional performing it.

Organotin Exposure and Vertebrate Reproduction: A Review.

Organotin (OTs) compounds are organometallic compounds that are widely used in industry, such as in the manufacture of plastics, pesticides, paints, and others. OTs are released into the environment by anthropogenic actions, leading to contact with aquatic and terrestrial organisms that occur in animal feeding. Although OTs are degraded environmentally, reports have shown the effects of this contamination over the years because it can affect organisms of different trophic levels. OTs act as endocrine-disrupting chemicals (EDCs), which can lead to several abnormalities in organisms. In male animals, OTs decrease the weights of the testis and epididymis and reduce the spermatid count, among other dysfunctions. In female animals, OTs alter the weights of the ovaries and uteri and induce damage to the ovaries. In addition, OTs prevent fetal implantation and reduce mammalian pregnancy rates. OTs cross the placental barrier and accumulate in the placental and fetal tissues. Exposure to OTs in utero leads to the accumulation of lipid droplets in the Sertoli cells and gonocytes of male offspring in addition to inducing early puberty in females. In both genders, this damage is associated with the imbalance of sex hormones and the modulation of the hypothalamic-pituitary-gonadal axis. Here, we report that OTs act as reproductive disruptors in vertebrate studies; among the compounds are tetrabutyltin, tributyltin chloride, tributyltin acetate, triphenyltin chloride, triphenyltin hydroxide, dibutyltin chloride, dibutyltin dichloride, diphenyltin dichloride, monobutyltin, and azocyclotin.

The obesogen tributyltin induces abnormal ovarian adipogenesis in adult female rats.

Tributyltin chloride (TBT) is an obesogen associated with various metabolic and reproductive dysfunctions after in utero exposure. However, few studies have evaluated TBT's obesogenic effect on adult ovaries. In this study, we assessed whether TBT's obesogenic effects resulted in adult ovarian adipogenesis and other reproductive abnormalities. TBT was administered to adult female Wistar rats, and their reproductive tract morphophysiology was assessed. We further assessed the ovarian mRNA/protein expression of genes that regulate adipogenesis. Rats exposed to TBT displayed abnormal estrous cyclicity, ovarian sex hormone levels, ovarian follicular development and ovarian steroidogenic enzyme regulation. Rats exposed to TBT also demonstrated abnormal ovarian adipogenesis with increased cholesterol levels, lipid accumulation, and PPARγ, C/EBP-ß and Lipin-1 expression. A negative correlation between the ovarian PPARγ expression and aromatase expression was observed in the TBT rats. Furthermore, TBT exposure resulted in reproductive tract atrophy, inflammation, oxidative stress and fibrosis. Ovarian dysfunctions also co-occurred with the uterine irregularities. Abnormal ovarian adipogenic markers occurring after TBT exposure may be associated with uterine irregularities. A positive correlation between the ovarian cholesterol levels and uterine inflammation was observed in the TBT rats. These findings suggest that TBT leads to ovarian obesogenic effects directly by abnormal adipogenesis and/or indirectly through adult reproductive tract irregularities.