Impact of STAT-signaling pathway on cancer-associated fibroblasts in colorectal cancer and its role in immunosuppression

Colorectal cancer(CRC)remains one of the most commonly diagnosed and deadliest types of cancer worldwide.CRC displays a desmoplastic reaction(DR)that has been inversely associated with poor prognosis;less DR is associated with a better prognosis.This reaction generates excessive connective tissue,in which cancer-associated fibroblasts(CAFs)are critical cells that form a part of the tumor microenvironment.CAFs are directly involved in tumorigenesis through different mechanisms.However,their role in immunosuppression in CRC is not well understood,and the precise role of signal transducers and activators of transcription(STATs)in mediating CAF activity in CRC remains unclear.Among the myriad chemical and biological factors that affect CAFs,different cytokines mediate their function by activating STAT signaling pathways.Thus,the harmful effects of CAFs in favoring tumor growth and invasion may be modulated using STAT inhibitors.Here,we analyze the impact of different STATs on CAF activity and their immunoregulatory role.

Commitment of human mesenchymal stromal cells to skeletal lineages is independent of their morphogenetic capacity

BACKGROUND Mesenchymal stromal cells(MSCs)are multipotent cell populations obtained from fetal and adult tissues.They share some characteristics with limb bud mesodermal cells such as differentiation potential into osteogenic,chondrogenic,and tenogenic lineages and an embryonic mesodermal origin.Although MSCs differentiate into skeletal-related lineages in vitro,they have not been shown to selforganize into complex skeletal structures or connective tissues,as in the limb.In this work,we demonstrate that the expression of molecular markers to commit MSCs to skeletal lineages is not sufficient to generate skeletal elements in vivo.AIM To evaluate the potential of MSCs to differentiate into skeletal lineages and generate complex skeletal structures using the recombinant limb(RL)system.METHODS We used the experimental system of RLs from dissociated-reaggregated human placenta(PL)and umbilical cord blood(UCB)MSCs.After being harvested and reaggregated in a pellet,cultured cells were introduced into an ectodermal cover obtained from an early chicken limb bud.Next,this filled ectoderm was grafted into the back of a donor chick embryo.Under these conditions,the cells received and responded to the ectoderm’s embryonic signals in a spatiotemporal manner to differentiate and pattern into skeletal elements.Their response to differentiation and morphogenetic signals was evaluated by quantitative poly-merase chain reaction,histology,immunofluorescence,scanning electron microscopy,and in situ hybridization.RESULTS We found that human PL-MSCs and UCB-MSCs constituting the RLs expressed chondrogenic,osteogenic,and tenogenic molecular markers while differentially committing into limb lineages but could not generate complex structures in vivo.MSCs-RL from PL or UCB were committed early to chondrogenic lineage.Nevertheless,the UCB-RL osteogenic commitment was favored,although preferentially to a tenogenic cell fate.These findings suggest that the commitment of MSCs to differentiate into skeletal lineages differs according to the source and is independent of their capacity to generate skeletal elements or connective tissue in vivo.Our results suggest that the failure to form skeletal structures may be due to the intrinsic characteristics of MSCs.Thus,it is necessary to thoroughly evaluate the biological aspects of MSCs and how they respond to morphogenetic signals in an in vivo context.CONCLUSION PL-MSCs and UCB-MSCs express molecular markers of differentiation into skeletal lineages,but they are not sufficient to generate complex skeletal structures in vivo.

Case Series of 11 Patients Operated with Axial-LIF Technique in a Single Center in Mexico

Introduction: Since the earliest description of spinal fusion in 1911 and later by Dr. Fred H. Albee, it has become one of the most commonly performed procedures by orthopedist and neurosurgeons. The spinal fusion is now used to treat a variety of indications, such as traumatic injuries, deformities, primary and secondary tumors, infections and degenerative conditions of the spine. The risk of iatrogenic injury during traditional anterior, posterior, and transforaminal open fusion surgery is significant. The axial lumbar interbody fusion (Axia-LIF) is a minimal invasive technique which uses the retroperitoneumpresacral anatomical corridor to fuse the lumbar vertebral bodies L4-L5-S1 avoiding manipulation of the annular ligament, paravertebral muscles and facet joints. Methods: In this retrospective series, we report all the cases made in the Centro Medico Naval in México City in two years. A total of eleven patients with degenerative disc disease and spondylolisthesis underwent Axia-LIF one or two level systems with a 36 months clinical and radiographic follow-up. The outcomes included Oswestry Disability Index (ODI) score and leg/back pain severity. Radiographic outcome was evaluated with dynamics and orthogonal x-ray, as well as lumbosacral tomography scan to evaluate fusion status. Results: Nine patients underwent Axia-LIF one level system (L5-S1) and the rest two levels system (L4-S1). Ten patients were fixated with transpedicular percutaneous screws and one with facets joints screws. No intraoperative complications were reported. The mean back pain severity improved 57% in 12 months, and the mean leg pain severity improved 50% in the same time (P < 0.001). Mean ODI scores improved 58%, from 60% ± 16% at baseline to 25% ± 8% at twelve months (P < 0.001). At one year, a patient developed pseudoarthrosis that required posterolateral arthrodesis with transpedicular percutaneous screws. At 36 months monitoring, 100% patients presented a total interbody fusion in the tomography scans. At final follow-up, mean ODI score improved 73% (16% ± 5%;P < 0.001). Conclusion: The Axial Lumbar Interbody Fusion has demonstrated to be a safe treatment for the degenerative disc disease L5-S1 and L4-S1. The patients who underwent one or two level Axia-LIF showed an improvement in ODI and back/leg pain severity scores, with no intraoperative complications. The use of this technique and its indications are still in controversy;nevertheless, its use has increased as for pathologies such as spondylitis, scoliosis, patients with residual pain with previous surgeries. We recommended complementary pedicular fixation to avoid complications and improved interbody fusion.

Occult hepatitis B virus infection among Mexican human immunodeficiency virus-1-infected patients

AIM: To determine the frequency of occult hepatitis B infection (OHBI) in a group of human immunodeficiency virus (HIV)-1+/ hepatitis B surface antigen negative (HBsAg)- patients from Mexico.

Tibolone modulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice

Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles （NFTs）; these hormones can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone （TIB） have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB （0.01 mg/kg and 1mg/kg, intragastrically for 12 weeks） on the content of total and hyperphosphorylated Tau （PHF-1） proteins and the regulation of GSK3β/Akt/PI3K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3β or PI3K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB： it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3β/Akt/PI3K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes.

Clinical,radiological and molecular diagnosis correlation in serum samples from patients with osteoarticular tuberculosis

Objective:To assess the role of polymerase chain reaction(PCR)in serum sauples,in the diagnosis of osteoarticular tuberculosis(OTB)in a setting where only clinical and imaging diagnoses determine the treatment.Methods:A total of 44 consecutive serum specimens were collected from clinically suspected OTB patients,based on clinical and radiological[X-ray or magnetic resonance imagng/computecl tomography]features.They were scrcened by in-house nested PCR.In addition,a few specimens were examined by Gram stain,acid-fast bacilli stain,histand routine bacterial culture.A total of 39 specimens were collected from patients suffering from other bone diseases of nontuberculous origin and included as negative controls.Results:of the 44 clinically suspected OTB patients,in-house nested PCR was positive in 40(91%)cases;PCR was negative in 38(97%)negative controls.Sensitivity and specificity of our in—house nested PCR was 90.3%and 97.4%,respectively.The PCR report was available within 48 h.It was possible to standardize serum PCR technique and in positive cases,a good n was observed in terms of an adequate treatment response.Conclusions:Nested PCR in serum samples is a rapid,highly sensitive and specific modality for OTB detection,PCR should be performed in addition to clinical evaluation,imaging studies,acidfast bacilli staining,culture and histopathology diagnosis,if possible.

Occult hepatitis B virus co-infection in human immunodeficiency virus-positive patients: A review of prevalence, diagnosis and clinical significance

The prevalence of human immunodeficiency virus(HIV) and hepatitis B virus(HBV) co-infection is high as they share similar mechanisms of transmission. The development and widespread use of highly sensitive tests for HBV diagnosis has demonstrated that a significant proportion of apparently healthy individuals with evidence of exposure to HBV continue to carry fully functional HBV DNA in their hepatocytes, a situation that predisposes them to the development of progressive liver disease and hepatocellular carcinoma. The presence of co-infections frequently influences the natural evolution of each of the participating infections present by either facilitating their virulence or competing for resources. Furthermore, the drugs used to treat these infections may also contribute to changes in the natural course of these infections, making the analysis of the impact of co-infection more difficult. The majority of studies has examined the impact of HIV on overt chronic hepatitis B, finding that co-infection carries an increased risk of progressive liver disease and the development of hepatocellular carcinoma. Although the effect of HIV on the natural history of occult hepatitis B infection(OBI) has not been fully assessed, all available data suggest a persisting risk of repeated flares of hepatitis and progressive liver disease. We describe studies regarding the diagnosis, prevalence and clinical significance of OBI in HIVpositive patients in this short review. Discrepancies in worldwide prevalence show the urgent need for the standardization of diagnostic criteria, as established by the Taormina statements. Ideally, standardized protocols for testing should be employed to enable the comparison of data from different groups. Additional studies are needed to define the differences in risk for OBI without HIV and in HIV-HBV co-infected patients with or without overt disease.

Effects of estrogen receptor modulators on cytoskeletal proteins in the central nervous system

Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer treatment and osteoporosis in postmenopausal women, as well as for the treatment of climacteric symptoms. Similar to estrogens, neuroprotective effects of estrogen receptor modulators have been described in different models. However, the mechanisms of action of these compounds in the central nervous system have not been fully described. We conducted a systematic search to investigate the effects of estrogen receptor modulators in the central nervous system, focusing on the modulation of cytoskeletal proteins. We found that raloxifene, tamoxifen, and tibolone modulate some cytoskeletal proteins such as tau, microtuble-associated protein 1（MAP1）, MAP2, neurofilament 38（NF38） by different mechanisms of action and at different levels： neuronal microfilaments, intermediate filaments, and microtubule-associated proteins. Finally, we emphasize the importance of the study of these compounds in the treatment of neurodegenerative diseases since they present the benefits of estrogens without their side effects.

Interstitial lung disease in rheumatoid arthritis:Current concepts in pathogenesis,diagnosis and therapeutics

Rheumatoid arthritis(RA) is the most common chronic autoimmune inflammatory joint disease. RA-associated interstitial lung disease(RA-ILD) is a major extraarticular complication and causes symptoms that lead to a deterioration in the quality of life, high utilization of health resources, and an increased risk of earlier mortality. Early in the course of RA-ILD, symptoms are highly variable, making the diagnosis difficult. Therefore, a rational diagnostic strategy that combines an adequate clinical assessment with the appropriate use of clinical tests, including pulmonary function tests and high-resolution computed tomography, should be used. In special cases, lung biopsy or bronchioalveolar lavage should be performed to achieve an early diagnosis. Several distinct histopathological subtypes of RA-ILD are currently recognized. These subtypes also have different clinical presentations, which vary in therapeutic response and prognosis. This article reviews current evidence about the epidemiology of RA-ILD and discusses the varying prevalence rates observed in different studies. Additionally, aspects of RA-ILD pathogenesis, including the role of cytokines and other molecules such as autoantibodies, as well as the evidence linking several drugs used to treat RA with lung damage will be discussed. Some aspects of the clinical characteristics of RA-ILD are noted, and diagnostic strategies are reviewed. Finally, this article analyzes current treatments for RA-ILD, including immunosuppressive therapies and biologic agents, as well as other therapeutic modalities. The prognosis of this severe complication of RA is discussed. Additionally, this paper examines updated evidence from studies identifying an association between drugs used for the treatment of RA and the development of ILD.

General Anesthesia for Cesarean Section in a Pregnant Woman with Immune Thrombocytopenic Purpura (ITP): A Case Report and Review of the Literature

Background: Management of immune thrombocytopenia (ITP) during pre- gnancy can be challenging, particularly by identifying a threshold for safe administration of neuraxial/general anesthesia and minimizing postpartum hemorrhage. There is controversy over the safety of cesarean section (CS) in ITP patients. In this case report, we discuss general anesthesia management in a patient with ITP with severe thrombocytopenia. Case Presentation: A 28-year-old female with relapsed/refractory ITP and severe thrombocytopenia underwent general anesthesia and emergent cesarean section with successful outcomes and minimal bleeding. Platelet counts before CS were 5000 × 109 L, the patient received 1 unit of platelets before the procedure and 1 unit of platelet and tranexamic acid 500 mg was injected slowly during the procedure. No evidence of bleeding and no complications were observed in the patient or newborn. Conclusions: In an emergent circumstance, general anesthesia and cesarean section procedure were performed safely in a patient with severe thrombocytopenia, no hemorrhagic complications were seen for this patient or neonate. Objective of This Manuscript: To share our experience of a safe emergent CS procedure and general anesthesia in a patient with severe thrombocytopenia. Our experience may guide the management of ITP patients in emergent delivery circumstances.

Interferon γ in patients with HIV/AIDS and suspicion or latent tuberculosis infection

Objective:To assess the usefulness of IGRA test(QuantiFERON? -Cell mediated immune) compared with the tuberculin skin test.Methods:A cross-sectional study was carried out in Mexico,25 infected patients with HIV-AIDS and the suspicion or with latent tuberculous infection （LTBI） who were】18 years of age and without treatment for tuberculosis（TB）,were enrolled in the study.Results:Median cluster of differentiation（CD4） count was 364 cells/μL and median HIV viral load was 50 copies/mL.Overall,20 patients（80%） had at least one positive diagnostic test for LTBI:four（16%） had a positive tuberculin skin test and 19（76%）,a positive QuantiFERON ? -tuberculosis.Conclusions:No agreement is found between the two diagnostic tests:k = -0.004,95%confidence interval（-0.2219,0.2210）.Additional longitudinal studies among HIV-infected populations with high prevalence of TB are needed to further assess the usefulness of IGRAs in this patient population.

Detection of <i>Helicobacter pylori</i>in dental plaque of mexican children by real-time PCR

Dental plaque in adult patients is well identified as a reservoir for Helicobacter pylori. This question still remains unclear in children. The aim of this study is to identify the presence of this bacterium in dental plaque of Mexican pediatric patients, using Real Time Polymerase Chain Reaction (qPCR). Forty patients from 2 to 11 years without dyspeptic symptoms were enrolled. Samples were collected from the subgingival space of the lingual side of the lower molars and cultured in selective medium. Therefore, qPCR analysis was conducted. According to the results obtained in this study, it was found that 35% of the pediatric population who participated tested qPCR positive for the presence of H. pylori in dental plaque samples. No significant associations were detected among isolation rate by gender or age. We found that dental plaque may be a reservoir for H. pylori. However, more research is needed to establish the way of the infection of pediatric population.

Long-term effect of autologous progenitor cell therapy to induce neo angiogenesis in patients with critical limb ischemia transplantated via intramuscular vs combined intramuscular and distal retrograde intra venous

Critical limb ischemia is a medical condition that decreases blood flow and limb oxygen supply;this disease in its late stages of progression leads to only two possible options: either surgical bypass revascularization or limb amputation. We investigated a novel method using autologous transplantation of progenitor cells derived from mobilized peripheral blood bone marrow mononuclear cells to evaluate its long-term effect as a cell therapy to induce neo-angiogenesis and restore blood flow in the affected ischemic limbs. A total of 20 ischemic limbs from critical limb ischemia diagnosed patients, non candidates to surgical revascularization were transplanted with autologous progenitor cells by either intramuscular combined with intravenous (group A) or intramuscular (group B) procedure. Patients were monitored during 31 months. Treatment efficacy was evaluated according to the following parameters: ankle brachial index which increased at a range of 0.29-1.0 in group A and 0.40-0.90 in group B;pain-free walking distance which increased at a range of 50-600 m in group A and 50-300 m in group B;and blood perfusion (measured by Laser Doppler) which increased at a range of 48-299 in group A and 135-225 in group B. We achieved 90% treated ischemic limbs free of amputation in both transplanted groups. Results here described provide a safe, efficient and minimally invasive therapy with progenitor cells to induce angiogenesis and preserve limbs from amputation in CLI diagnosed patients.

Risk Factors for Starr-Edwards Prosthetic Valve Dysfunction: New Insights into an Old Prosthesis

Background: Starr-Edwards prosthetic valves were used for valve replacement, but due to their high thrombogenic risk, they were withdrawn from market. Nevertheless, there are some cases of Starr-Edwards prosthetic valve carriers that have shown long-term survival reaching up to 50 years. The objective of this study was to determine survival in 12 patients with mechanical Starr-Edwards?prosthetic valve and risk factors for predicting valve dysfunction. Methods: Cross-sectional study of patients who had valve replacement with a Starr-Edwards prosthetic valve in a single center from 1968 to 1990. Socio-demographic data, valvular dysfunction variables and mortality were recorded. Logistic regression models to determine valvular dysfunction were constructed. Survival was analyzed with Cox regression and Kaplan-Meier survival curves. Results: A total of 12 patients were analyzed. The median age was 59 years (48.5 - 64). Eleven patients had normal right and left ventricular function. The most common cause of valve replacement was rheumatic valve disease (75%) and it was more frequently in mitral position (50%). Valvular dysfunction was detected in 3 patients (25%). Atrial fibrillation had the highest association with valvular dysfunction (P = 0.005). Stroke was seen in 25% of the population and the overall mortality was 33.3%. Conclusions: The survival of patients with Starr-Edwards prosthetic valve was 66.66% in the 50-year follow-up. Atrial fibrillation had the highest association with prosthetic valvular dysfunction.

Obesity is associated with the Arg389Gly ADRB1 but not with the Trp64Arg ADRB3 polymorphism in children from San Luis Potosí and León,México

This research was designed to analyze the possible associations of Arg389 Gly ADRB1 and Trp64 Arg ADRB3polymorphisms in children with obesity.A cross-sectional study included 1,046 school-age Mexican participants（6-12 years old） from the cities of San Luis Potosi and Leon.Children were classified as non-obese or obese according to their body mass index（BMI） percentile;obese children had a BMI≥95th percentile for sex and age.Biochemical data were collected.Polymorphisms were detected using TaqMan qPCR assay.A logistic regression analysis was used to calculate the risk of obesity based on genotypes.Differences were found between groups where obese children had a significant increase in systolic and diastolic blood pressure,fasting plasma glucose,insulin,HOMAIR,LDL-cholesterol,triglycerides,and lower HDL-cholesterol compared with the normal weight group（P 〈 0.05）.The distribution of allele frequency in the population was Arg = 87.4 and Gly = 12.6（Hardy Weinberg equilibrium x^2= 3.16,P = 0.07）;Trp = 81.5 and Arg= 18.5（Hardy Weinberg equilibrium x^2 = 2.2,P = 0.14） for ADRB1 and ADRB3,respectively.Even though no different frequencies of Arg389 Gly polymoiphism between groups were found（P = 0.08）,children carriers of one Gly389,ADRB1 allele had a risk for obesity of OR = 1.40（95%CI,1.03-1.90,P =0.03） after adjustment for age and gender.No other association was found for Trp64 Arg ADRB3 polymorphism.Only the Arg389 Gly ADRB1 polymorphism was associated with risk for obesity in Mexican children.

CXCR4+ and SDF-1+ Bone Marrow Cells Are Mobilized into the Blood Stream in Acute Myocardial Infarction and Acute Ischemia

Cell therapy has shown beneficial effects on ventricular function and tissue regeneration in patients with acute and chronic myocardial infarction, although with diverse grades of variability in the results, possibly by proportion, subtype and cell cycle status. Objective: Identify and phenotypically characterize, via CXCR4 and SDF-1 expression, the bone marrow cell subpopulations that are mobilized into the bloodstream in patients with Acute Myocardial Infarction (AMI) and Acute Ischemia (AI) such as acute angina and Chronic Ischemia (CI) such as chronic stable angina, and also determine the cell cycle status of these cells. Method: Patients with AMI and AI were recruited in the ICCU, and patients with CI in the departments of cardiology and cardiovascular surgery. The quantification of cellular subpopulations was made by cytofluorometry with a FACS caliburcyto fluorometry (Becton Dickinson) with specific FITC-labeled anti human monoclonal antibodies against CD34, CD133, CD117, CD48, CXCR4, SDF-1 and Ki67 (Becton Dickinson). Serum concentration of IL-6 and IL-8 were determined by a sequential solid phase chemiluminescent assay performed in a SIEMENS IMMULITE 1000 Analyzer. Statistical analysis was made with the SPSS version 20.0 for Windows. A p value 3/ml) than that in AI (9.2 ± 1.3 × 103/ml) and CI (6.6 ± 1.1 × 103/ml) patients (p p = 0.22 to 0.39), but interestingly in AMI and AI patients, cells were CXCR4+ in almost half of these mobilized cells, although the proportion was significantly higher in AMI patients (46.8% ± 7.1% to 55.7% ± 6.3% vs 23% ± 1.6% to 28.4% ± 2.1%, p = 0.03 to 0.05). A similar behavior was observed with the Ki67 antibody (29.9% ± 2.1% to 36.1% ± 6.3% vs 10% ± 1.2% to 24% ± 1.1%, p = 0.001 to 0.05). Bivariate analysis of the results showed a significant correlation of the cell proportion in AMI but not in AI and CI patients (p = 0.001 to 0.05;0.12 to 0.87 and 0.17 to 0.92 respectively). The amount of myocardial tissue infarcted did not show any correlation with the amount of cellular subpopulations mobilized to peripheral blood (r = 0.10 to 0.20;p = 0.21 to 0.64) from the bone marrow. Conclusion: The proportion of cellular subpopulations with regenerative potential mobilized to circulation during an event of Acute Myocardial Infarction is significantly higher than during an event of acute angina and chronic stable angina, with a significant proportion of mobilized cells that expressed CXCR4, most of which were already in some of the cell cycle phases.

Hypersensitivity to Aspirin as a Factor for Poor Control in Hereditary Angioedema

Background: Hereditary angioedema (HAE) is a primary immunodeficiency disorder characterized by C1 complement inhibitor deficiency and unregulated activation of complement. Aspirin hypersensitivity is related to an increase in the amount of leukotrienes with eosinophil and mast cell activation and increased levels of glandular kallikrein with upregulated local conversion of bradykinin. Both conditions can be present in the same patient. Objectives: We present five patients with HAE;they were all being treated in similar ways according to the therapeuthic options available in our institute (danazol). However, three of them had recurrent episodes of angioedema;in these cases, it was identified aspirin hypersensitivity as a cause of poor disease control. A review of the literature is included. Case Presentation: We present the cases of four females and one male (age range 21 - 58 years) with type I HAE. Subjects were all ISSSTE beneficiaries (state workers) treated at the National Medical Center “20 de Noviembre”. Aspirin hypersensitivity was identified in three patients. Elimination of NSAIDs along with dietary elimination of high salicylate-containing foods improved control of angioedema crisis (severe and/ or recurrent episodes). Discussion: Aspirin hypersensitivity was identified as a factor for poor control in our patients with HAE. Such cases improved with dietary elimination of high salicylate-containing foods and avoidance of NSAIDs. Conclusions: This is the first report of patients with HAE and aspirin hypersensitivity as a cause of poor control. We recommend a deliberate search of these comorbidities, especially in cases of poor disease control. Further studies are needed to continue the investigation on this topic.

Increased serotonin concentration and tryptophan hydroxylase activity in reproductive organs of copulator males:a case of adaptive plasticity

Individual male rats may systematically display or not copulatory behavior when paired with receptive females. Although these phenotypes are associated with differences in brain organization and function, they might also do so at the level of the reproductive organs. We then used high performance liquid chromatography to quantify serotonin concentration and the activity of tryptophan hydroxylase in the reproductive organs of copulator and non-copulator males. Sexual behavior display was compared between groups and parameters of fertility and reproductive fitness were determined for copulator males. Copulator males had higher concentrations of serotonin in the epididymis, testicle and ventral prostate than their non-copulator counterparts, as it was found for epididymal and testicular tryptophan hydroxylase activity. However, preliminary data shows that serotonin elevation occurs in copulator males only until they have accumulated several sexual encounters, so it might be a response to genital gratification or sexual rewarding. Interestingly, only epididymal serotonin concentration correlated with reproductive fitness, offspring number, mating success and seminal plug volume in copulator males. Our results support that copulator and non-copulator male rats feature a phenotype-specific serotoninergic tone in the epididymis, testicle and ventral prostate gland. The observation documenting that epididymal serotonin concentration correlated with parameters that monitor male fertility and reproductive fitness in copulator males predicts that epididymal factors increase their chances of parenting offspring.