Downregulation of Serotonergic System Components in an Experimentally Induced Cryptorchidism in Rabbits.

Cryptorchidism (CO) or undescended testes is defined as the failure of one or both testes to be positioned inside the scrotum. Typically, cryptorchidism is detected at birth or shortly thereafter, and in humans, it is considered to be part of the testicular dysgenesis syndrome (TDS), a complex pathology regarding the male reproductive system that apparently involves the interaction of both genetic and environmental harmful factors, mainly during embryonic development. Serotonin (5-HT) is an ancient molecule that participates in a broad range of body functions, and in recent years, its importance in reproduction has started to be elucidated. In male pathologies such as infertility, varicocele, erectile dysfunction, and primary carcinoid tumors, an increase in 5-HT concentration or its metabolites in the blood, semen, and urine has been directly related; nevertheless, the role of 5-HT in CO remains unknown. In the present work, our goal was to answer two important questions: (1) whether some serotonergic system components are present in adult male Oryctolagus cuniculus (chinchilla rabbit) and (2) if there are changes in their expression in an experimental model of CO. Using histological, molecular, and biochemical approaches, we found the presence of some serotonergic system components in the adult chinchilla rabbit, and we demonstrated that its expression is downregulated after CO was pharmacologically induced. Although we did not test the role of 5-HT in the etiology of CO, our results suggest that this indoleamine could be important for the regulation of steroidogenesis and spermatogenesis processes in the chinchilla rabbit during adulthood. Finally, in parallel experimental series, we found downregulation of kynurenine concentration in COI rabbits when compared to control ones, suggesting that CO could be affecting the kynurenine pathway and probably testicular immune privilege which in turn could lead to infertility/sterility conditions in this disorder.

Expanding the concept of serotoninomics: perspectives for serotonin studies in the 20's of the 21st century.

Surely, Vittorio Erspamer, discoverer of Enteramine in 1935, and Irvine Page, Maurice M. Rapport and Arda Green, discoverers of Serotonin in 1948, never imagined the biological importance that this fundamental molecule has in the living beings of our planet; from its physiological, passing through endocrine, neural, developmental and reproductive functions and even its role in evolution. For this reason, our workgroup is commemorating these researchers and celebrating their great discovery, which deeply influenced science and medicine, in the present perspective article. As a consequence of their seminal work, and the work of many other researchers in the field of serotonin over the following years, now we stand in front of the practical concept of "Serotoninomics," which we think will contribute to find out precise answers regarding basic, clinical, and translational research related to serotonin, just as the emerging medical and "omics" sciences have done before.

National sex- and age-specific burden of blindness and vision impairment by cause in Mexico in 2019: a secondary analysis of the Global Burden of Disease Study 2019.

Background: Reliable national estimations for blindness and vision impairment are fundamental to assessing their burden and developing public health policies. However, no comprehensive analysis is available for Mexico. Therefore, in this observational study we describe the national burden of blindness and vision loss by cause and severity during 2019. Methods: Using public data from the Global Burden of Disease (GBD) study 2019, we present national prevalence and years lived with disability (YLDs) counts and crude and age-standardized rates (per 100,000 people) of total, severity- and cause-specific blindness and vision impairment with 95% uncertainty intervals (UIs) by sex and age group. Findings: In Mexico, the burden of blindness and vision impairment was estimated at 11.01 million (95% UI, 9.25-13.11) prevalent cases and 384.96 thousand (259.57-544.24) YLDs during 2019. Uncorrected presbyopia caused the highest burden (6.06 million cases, 4.36-8.08), whereas severe vision loss and blindness affected 619.40 thousand (539.40-717.73) and 513.84 thousand (450.59-570.98) people, respectively. Near vision loss and refraction disorders caused 78.7% of the cases, whereas neonatal disorders and age-related macular degeneration were among the least frequent. Refraction disorders were the main cause of moderate and severe vision loss (61.44 and 35.43%), and cataracts were the second most frequent cause of blindness (26.73%). Females suffered an overall higher burden of blindness and vision impairment (54.99% and 52.85% of the total cases and YLDs), and people >50 years of age suffered the highest burden, with people between 70 and 74 years being the most affected. Interpretation: Vision loss represents a public health problem in Mexico, with women and older people being the most affected. Although the causes of vision loss contribute differentially to the severity of visual impairment, most of the impairment is avoidable. Consequently, a concerted effort at different levels is needed to alleviate this burden. Funding: This study received no funding.

The Clinical Utility of lncRNAs and Their Application as Molecular Biomarkers in Breast Cancer.

Given their tumor-specific and stage-specific gene expression, long non-coding RNAs (lncRNAs) have demonstrated to be potential molecular biomarkers for diagnosis, prognosis, and treatment response. Particularly, the lncRNAs DSCAM-AS1 and GATA3-AS1 serve as examples of this because of their high subtype-specific expression profile in luminal B-like breast cancer. This makes them candidates to use as molecular biomarkers in clinical practice. However, lncRNA studies in breast cancer are limited in sample size and are restricted to the determination of their biological function, which represents an obstacle for its inclusion as molecular biomarkers of clinical utility. Nevertheless, due to their expression specificity among diseases, such as cancer, and their stability in body fluids, lncRNAs are promising molecular biomarkers that could improve the reliability, sensitivity, and specificity of molecular techniques used in clinical diagnosis. The development of lncRNA-based diagnostics and lncRNA-based therapeutics will be useful in routine medical practice to improve patient clinical management and quality of life.

Transcriptomics and RNA-Based Therapeutics as Potential Approaches to Manage SARS-CoV-2 Infection.

SARS-CoV-2 is a coronavirus family member that appeared in China in December 2019 and caused the disease called COVID-19, which was declared a pandemic in 2020 by the World Health Organization. In recent months, great efforts have been made in the field of basic and clinical research to understand the biology and infection processes of SARS-CoV-2. In particular, transcriptome analysis has contributed to generating new knowledge of the viral sequences and intracellular signaling pathways that regulate the infection and pathogenesis of SARS-CoV-2, generating new information about its biology. Furthermore, transcriptomics approaches including spatial transcriptomics, single-cell transcriptomics and direct RNA sequencing have been used for clinical applications in monitoring, detection, diagnosis, and treatment to generate new clinical predictive models for SARS-CoV-2. Consequently, RNA-based therapeutics and their relationship with SARS-CoV-2 have emerged as promising strategies to battle the SARS-CoV-2 pandemic with the assistance of novel approaches such as CRISPR-CAS, ASOs, and siRNA systems. Lastly, we discuss the importance of precision public health in the management of patients infected with SARS-CoV-2 and establish that the fusion of transcriptomics, RNA-based therapeutics, and precision public health will allow a linkage for developing health systems that facilitate the acquisition of relevant clinical strategies for rapid decision making to assist in the management and treatment of the SARS-CoV-2-infected population to combat this global public health problem.

Incidence, Mortality, and Trends of Prostate Cancer in Mexico from 2000 to 2019: Results from the Global Burden of Disease Study 2019.

In 2019, the Global Burden of Disease (GBD) estimated that prostate cancer (PC) was the 16th most common cause of death globally in males. In Mexico, PC epidemiology has been studied by a number of metrics and over various periods, although without including the most up-to-date estimates. Herein, we describe and compare the burdens and trends of PC in Mexico and its 32 states from 2000 to 2019. For this study, we extracted online available data from the GBD 2019 to estimate the crude and age-standardized rates (ASR per 100,000 people) of the incidence and mortality of PC. In Mexico, PC caused 27.1 thousand (95% uncertainty intervals, 20.6-36.0 thousand) incident cases and 9.2 thousand (7.7-12.7 thousand) deaths in males of all ages in 2019. Among the states, Sinaloa had the greatest ASR of incidence, and Guerrero had the highest mortality. The burden of PC showed an increasing trend, although the magnitude of change differed between metrics and locations. We found both an increasing national trend and subnational variation in the burden of PC. Our results confirm the need for updated and timely estimates to design effective diagnostic and treatment campaigns in locations where the burden of PC is the highest.

The promising role of new molecular biomarkers in prostate cancer: from coding and non-coding genes to artificial intelligence approaches.

BACKGROUND: Risk stratification or progression in prostate cancer is performed with the support of clinical-pathological data such as the sum of the Gleason score and serum levels PSA. For several decades, methods aimed at the early detection of prostate cancer have included the determination of PSA serum levels. The aim of this systematic review is to provide an overview about recent advances in the discovery of new molecular biomarkers through transcriptomics, genomics and artificial intelligence that are expected to improve clinical management of the prostate cancer patient. METHODS: An exhaustive search was conducted by Pubmed, Google Scholar and Connected Papers using keywords relating to the genetics, genomics and artificial intelligence in prostate cancer, it includes "biomarkers", "non-coding RNAs", "lncRNAs", "microRNAs", "repetitive sequence", "prognosis", "prediction", "whole-genome sequencing", "RNA-Seq", "transcriptome", "machine learning", and "deep learning". RESULTS: New advances, including the search for changes in novel biomarkers such as mRNAs, microRNAs, lncRNAs, and repetitive sequences, are expected to contribute to an earlier and accurate diagnosis for each patient in the context of precision medicine, thus improving the prognosis and quality of life of patients. We analyze several aspects that are relevant for prostate cancer including its new molecular markers associated with diagnosis, prognosis, and prediction to therapy and how bioinformatic approaches such as machine learning and deep learning can contribute to clinic. Furthermore, we also include current techniques that will allow an earlier diagnosis, such as Spatial Transcriptomics, Exome Sequencing, and Whole-Genome Sequencing. CONCLUSION: Transcriptomic and genomic analysis have contributed to generate knowledge in the field of prostate carcinogenesis, new information about coding and non-coding genes as biomarkers has emerged. Synergies created by the implementation of artificial intelligence to analyze and understand sequencing data have allowed the development of clinical strategies that facilitate decision-making and improve personalized management in prostate cancer.

Prevalence, main serovars and anti-microbial resistance profiles of non-typhoidal Salmonella in poultry samples from the Americas: A systematic review and meta-analysis.

Poultry and poultry-derived products such as meat and eggs are among the main sources of non-typhoidal Salmonella (NTS) transmission to humans. Therefore, we performed a systematic review and used random-effects meta-analyses to (1) estimate the prevalence of NTS in poultry samples from birds, products and subproducts and environmental samples, (2) examine the diversity and frequency of their serovars and (3) estimate the prevalence and profiles of anti-microbial resistance (AMR) in NTS isolates reported in studies from the Americas. We included 157 studies from 15 countries comprising 261,408 poultry samples and estimated an overall pooled prevalence of 17.9% (95% Confidence Interval: 10.8-26.3) in birds, 21.8% (17.7-26.1) in products and subproducts and 29.5% (24.2-35.1) in environmental samples. At the national level, the prevalence of NTS was heterogeneous across countries with the highest values in Mexico, the United States and Canada. In total, 131 serovars were identified from 13,388 isolates; Heidelberg, Kentucky, Enteritidis and Typhimurium were the most prevalent in the overall top 10 ranking (range 6.5%-20.8%). At the national level, Enteritidis and Typhimurium were identified in most of the countries, though with national differences in their ranks. The prevalence of AMR increased from 24.1% for 1 antibiotic to 36.2% for 2-3 antibiotics and 49.6% for ≥ 4 antibiotics. Kentucky, Heidelberg, Typhimurium and Enteritidis were the serovars with the highest prevalence of AMR. Besides, tetracycline, ampicillin, streptomycin, ceftiofur and amoxicillin-clavulanic acid were the most frequent antibiotics to which NTS showed resistance. In conclusion, NTS was distributed through the avian production chain with high and heterogeneous values of prevalence in poultry samples. Besides, there were distinctive patterns of serovars distribution across countries and an alarming prevalence of AMR among zoonotic serovars.

Transcriptome Analysis Identifies GATA3-AS1 as a Long Noncoding RNA Associated with Resistance to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients.

Breast cancer is one of the leading causes of mortality in women worldwide, and neoadjuvant chemotherapy has emerged as an option for the management of locally advanced breast cancer. Extensive efforts have been made to identify new molecular markers to predict the response to neoadjuvant chemotherapy. Transcripts that do not encode proteins, termed long noncoding RNAs (lncRNAs), have been shown to display abnormal expression profiles in different types of cancer, but their role as biomarkers in response to neoadjuvant chemotherapy has not been extensively studied. Herein, lncRNA expression was profiled using RNA sequencing in biopsies from patients who subsequently showed either response or no response to treatment. GATA3-AS1 was overexpressed in the nonresponder group and was the most stable feature when performing selection in multiple random forest models. GATA3-AS1 was experimentally validated by quantitative RT-PCR in an extended group of 68 patients. Expression analysis confirmed that GATA3-AS1 is overexpressed primarily in patients who were nonresponsive to neoadjuvant chemotherapy, with a sensitivity of 92.9% and a specificity of 75.0%. The statistical model was based on luminal B-like patients and adjusted by menopausal status and phenotype (odds ratio, 37.49; 95% CI, 6.74-208.42; P = 0.001); GATA3-AS1 was established as an independent predictor of response. Thus, lncRNA GATA3-AS1 is proposed as a potential predictive biomarker of nonresponse to neoadjuvant chemotherapy.

Modulation of Renal Function in a Metabolic Syndrome Rat Model by Antioxidants in Hibiscus sabdariffa L.

Metabolic syndrome (MS) is the association of three or more pathologies among which obesity, hypertension, insulin resistance, dyslipidemia, and diabetes are included. It causes oxidative stress (OS) and renal dysfunction. Hibiscus sabdariffa L. (HSL) is a source of natural antioxidants that may control the renal damage caused by the MS. The objective of this work was to evaluate the effect of a 2% HSL infusion on renal function in a MS rat model induced by the administration of 30% sucrose in drinking water. 24 male Wistar rats were divided into 3 groups: Control rats, MS rats and MS + HSL rats. MS rats had increased body weight, systolic blood pressure, triglycerides, insulin, HOMA index, and leptin (p ≤ 0.04). Renal function was impaired by an increase in perfusion pressure in the isolated and perfused kidney, albuminuria (p ≤ 0.03), and by a decrease in clearance of creatinine (p ≤ 0.04). The activity of some antioxidant enzymes including the superoxide dismutase isoforms, peroxidases, glutathione peroxidase, glutathione-S-transferase was decreased (p ≤ 0.05). Lipoperoxidation and carbonylation were increased (p ≤ 0.001). The nitrates/nitrites ratio, total antioxidant capacity, glutathione levels and vitamin C were decreased (p ≤ 0.03). The treatment with 2% HSL reversed these alterations. The results suggest that the treatment with 2% HSL infusion protects renal function through its natural antioxidants which favor an improved renal vascular response. The infusion contributes to the increase in the glomerular filtration rate, by promoting an increase in the enzymatic and non-enzymatic antioxidant systems leading to a decrease in OS and reestablishing the normal renal function.

Indolaminergic System in Adult Rat Testes: Evidence for a Local Serotonin System.

Serotonin (5-HT) is member of a family of indolamine molecules that participate in a wide variety of biological processes. Despite its important role in the regulation of local blood systems, little is known about the physiological function of 5-HT in reproductive organs, its functional implications, and its role in the reproduction of mammals. In the present work, we evaluated the localization and distribution of 5-HT (using histochemical analysis of indolamines) and different components of the serotoninergic system in rat testes. We detected local synthesis and degradation through immunofluorescence and western blot analyses against the TPH1, MAOA, 5-HTT, and VMAT1 serotonin transporters. We also identified the localization and distribution of the 5-HT1B, 5-HT2A, and 5-HT3A receptors. RT-PCR results showed the presence of the Tph1, Maoa, Slc6a4, and Htr3a genes in testes and in the brain stem (Tph1 was used as a negative control). High-performance liquid chromatography was used to determine the presence of 5-HT and the activity of tryptophan hydroxylase in testes homogenates in vitro. Our observations suggest that TPH1 activity and local 5-HT synthesis befall in rat testes. We propose that 5-HT could participate in the regulation of testosterone synthesis and in the spermatogenesis process via local serotoninergic system. However, more studies are needed before concluding that rat testes, or those of other mammals, contain an active form of tryptophan hydroxylase and produce 5-HT.

Impact of heat stress on the reproductive performance and physiology of ewes: a systematic review and meta-analyses.

High values of ambient temperature and relative humidity negatively affect livestock because they induce heat stress. In heat-stressed ewes, the reproduction is affected, although there apparently is a different effect depending on their physiological status. Therefore, we conducted a systematic review and meta-analyses to estimate the effect of heat stress on the reproductive performance and physiology of cycling or pregnant ewes. We included studies in which pregnant or cycling ewes were exposed to heat stress and included a comparison group. We assessed the risk of bias and used meta-analyses that included the period of exposure to calculate pooled estimates. We included 36 studies comprising 20,626 ewes, and the meta-analyses demonstrated that heat stress decreased 7.09 h (95% CI, - 10.75, - 3.43) the duration of estrus in cycling ewes but increased 0.57 days (95% CI, 0.23, 0.92) the length of the cycle, although differentially affecting the expression of sexual behavior. Heat-stressed cycling ewes had greater odds of embryo mortality (OR = 12.36; 95% CI, 7.10, 21.54) and a decreased chance of impregnation (OR = 0.41; 95% CI, 0.23, 0.75). In heat-stressed pregnant ewes, placental and fetal weights were reduced, respectively in 183.62 g (95%CI, - 252.25, - 114.99) and 1665.18 g (95% CI, - 2136.82, - 1193.55). Heat stress increased ewes' body temperature 1.13 °C (95% CI, 0.85, 1.42) and respiratory rate 93.53 breaths/min (95% CI, 63.5, 123.5) without affecting heart rate. In a sub-group analyses, the period of exposure was shown to cause a significant effect. In conclusion, our results revealed a differential effect of heat stress that depends on both the physiological status of ewes and the period of exposure, and identify susceptible reproductive stages during which the severe effects of heat stress can be prevented/ameliorated.

Epigallocatechin-3-gallate protects the testis from damage generated by experimental cryptorchidism in rabbits.

Cryptorchidism (CO) is a risk factor for infertility in men. It is associated with an increase in oxidative stress which alters the differentiation of the gonocytes to spermatogonia. Epigallocatechin-3-gallate (EGCG) is an antioxidant that acts as a free radical scavenger and activates the antioxidant enzymes. The aim of this work was to investigate if EGCG plays a role in the protection of the testicle from alterations generated by CO and its possible mechanism. Male rabbits 7 days old were divided into four groups and distributed as follows: 1) control (C) treated with EGCG vehicle (V) (C/V); 2) C with administration of EGCG from 65 to 120 days postpartum (dpp) (C/EGCG); 3) CO induced by administration of 17ß-estradiol plus EGCG vehicle (CO/V) and 4) CO plus EGCG administration (CO/EGCG). The animals were euthanized at 120 dpp and their testes were processed to evaluate lipid peroxidation, activities of superoxide dismutase (SOD) and catalase (CAT) enzymes as well as serum testosterone (T) concentrations. In addition, the rates of apoptosis, cell proliferation and histological alterations were determined. The CO/EGCG group showed a significant reduction in lipid peroxidation, a significant increase in the anti-oxidant enzyme activities and concentrations of T. Also, there was a significant decrease in the histological alterations, absence of gonocytes and active spermatogenesis when compared with CO/V group. These results show that EGCG reduces lipid peroxidation and increases the activity of the endogenous anti-oxidant system which protects the testes from alterations produced by oxidative stress generated during experimental CO.

Incidence of Intestinal Infectious Diseases due to Protozoa and Bacteria in Mexico: Analysis of National Surveillance Records from 2003 to 2012.

BACKGROUND: According to national epidemiological surveillance records, in Mexico six intestinal infectious diseases (IID) are among the top infectious communicable diseases. However, their incidence, relative importance, and spatial patterns have not been studied in detail. AIMS: We examine the epidemiology of IID due to bacteria and protozoa to identify which diseases are most important at two spatial scales, what is their integrated importance locally, and how their incidence correlates with Human Development Index (HDI). METHODS: We retrieved yearly number of new cases of eight IID from the national epidemiological morbidity report from 2003 to 2012 at the national level, by state, and to assess such information at a higher spatial resolution we included the municipalities for Mexico City. However, no comparisons were made to other municipalities due to unavailability of data. We compared incidence, obtained the disease-specific relative importance, and inspected spatial patterns for the integrated incidence. Finally, we tested whether HDI is correlated with incidence. RESULTS: We found that, except for two diseases, the relative importance of the other six IID contrasted not only between the national level and Mexico City, but also among states and municipalities in Mexico City. Besides, at both scales the distribution of the incidence showed disease-specific spatial patterns. Finally, there was a lack of consistent correlation between HDI and individual IID at both scales. CONCLUSION: Our results emphasize the need for local disease-focused selective models for control and prevention of IID. The maps displaying our analyses of epidemiological similarities may be used in orienting such effort.

The use of long non-coding RNAs as prognostic biomarkers and therapeutic targets in prostate cancer.

Prostate cancer is the most common cancer in men and the second leading cause of cancer-related deaths. The most used biomarker to detect prostate cancer is Prostate Specific Antigen (PSA), whose levels are measured in serum. However, it has been recently established that molecular markers of cancer should not be based solely on genes and proteins but should also reflect other genomic traits; long non-coding RNAs (lncRNAs) serve this purpose. lncRNAs are transcripts of >200 bases that do not encode proteins and that have been shown to display abnormal expression profiles in different types of cancer. Experimental studies have highlighted lncRNAs as potential biomarkers for prognoses and treatments in patients with different types of cancer, including prostate cancer, where the PCA3 lncRNA is currently used as a diagnostic tool and management strategy. With the development of genomic technologies, particularly next-generation sequencing (NGS), several other lncRNAs have been linked to prostate cancer and are currently under validation for their medical use. In this review, we will discuss different strategies for the discovery of novel lncRNAs that can be evaluated as prognostic biomarkers, the clinical impact of these lncRNAs and how lncRNAs can be used as potential therapeutic targets.

Epigenetic and risk factors of testicular germ cell tumors: a brief review.

Testicular germ cell cancer (TGCT) is the most common malignancy among young adult males, which has become important due to its increased incidence and mortality in the population worldwide. The etiology is multifactorial. Recent studies have shown some associations between the development of isolated TGCT and certain risk factors, such as exposure to endocrine disruptors, cryptorchidism, and family history of cancer, in order to identify the key pieces in carcinogenesis. Some of the most important findings in recent years is the association of different genes, such as c-KIT/KITLG, expression of the miR-371-373 cluster and protein expression as c-KIT and POU5F1 in the development of this neoplasia, and the identification of new molecular markers as TGFBR3 gene, identifying aberrant methylation patterns in promoter regions of several genes, expression of miR-1297 which regulates PTEN and protein expression as DMTR1. In the future, a multidisciplinary research strategy could provide valuable new insights into the etiology of TGCTs, which support clinical diagnosis of TGCT in the next years to increase survival in this kind of patients.

The face of female dominance: Women with dominant faces have lower cortisol.

The human face displays a wealth of information, including information about dominance and fecundity. Dominance and fecundity are also associated with lower concentrations of the stress hormone cortisol, suggesting that cortisol may negatively predict facial dominance and attractiveness. We digitally photographed 61 women's faces, had these images rated by men and women for dominance, attractiveness, and femininity, and explored relationships between these perceptions and women's salivary cortisol concentrations. In a first study, we found that women with more dominant-appearing, but not more attractive, faces had lower cortisol levels. These associations were not due to age, ethnicity, time since waking, testosterone, or its interaction with cortisol. In a second study, composite images of women with low cortisol were perceived as more dominant than those of women with high cortisol significantly more often than chance by two samples of viewers, with a similar but non-significant trend in a third sample. However, data on perceptions of attractiveness were mixed; low-cortisol images were viewed as more attractive by two samples of US viewers and as less attractive by a sample of Mexican viewers. Our results suggest that having a more dominant-appearing face may be associated with lower stress and hence lower cortisol in women, and provide further evidence regarding the information content of the human face.

Serotonin in testes of bat Myotis velifer during annual reproductive cycle: expression, localization, and content variations.

The mechanism of reproduction in mammals is very complex and in some cases is quite particular. For example in some bat species, the male presents a reproductive mechanism characterized by an annual testicular cycle that goes from recrudescence to regression (spermatogenesis to inactivity period, respectively). After recrudescence, the spermatozoa arrive at epididymis and wait to be expelled at the time of ejaculation during the mating period, which occurs some months later. Because serotonin (5-HT) has gained reproductive importance in the last years, the aim of the present study was to analyze the expression of this indolamine and both tryptophan hydroxylase and monoamine oxidase isoform A-enzymes involved in its metabolism-in Myotis velifer testes, a seasonal reproductive bat species that shows temporal asynchrony in its sexual cycle, across the principal periods of their reproductive cycle. By using both Falck-Hillarp histochemistry and immunofluorescence techniques, we found serotonin in vesicles of Leydig cells and probably Sertoli cells too; interestingly, both intracellular localization and concentration was variable across the different stages of the reproductive cycle, being lower during spermatogenesis phase and increasing during the mating phase. These results suggest that 5-HT is present in bat testes and it could play an important role in testicular function during their reproductive cycle.

Evidence of 5-HT components in human sperm: implications for protein tyrosine phosphorylation and the physiology of motility.

Serotonin (5-hydroxytryptamine; C(10)H(12)N(2)O (5-HT)) is produced in the CNS and in some cells of peripheral tissues. In the mammalian male reproductive system, both 5-HT and tryptophan hydroxylase (TPH) have been described in Leydig cells of the testis and in principal cells of the caput epididymis. In capacitated hamster sperm, it has been shown that 5-HT promotes the acrosomal reaction. The aim of this work was to explore the existence of components of the serotoninergic system and their relevance in human sperm physiology. We used both immunocytochemistry and western blot to detect serotoninergic markers such as 5-HT, TPH1, MAO(A), 5-HT(1B), 5-HT(3), and 5HT(T); HPLC for TPH enzymatic activity; Computer Assisted Semen Analysis assays to measure sperm motility parameters and pharmacological approaches to show the effect of 5-HT in sperm motility and tyrosine phosphorylation was assessed by western blot. We found the presence of serotoninergic markers (5-HT, TPH1, MAO(A), 5-HT(1B), 5-HT(2A), 5-HT(3), 5-HT(T), and TPH enzymatic activity) in human sperm. In addition, we observed a significant increase in tyrosine phosphorylation and changes in sperm motility after 5-HT treatment. In conclusion, our data demonstrate the existence of components of a serotoninergic system in human sperm and support the notion for a functional role of 5-HT in mammalian sperm physiology, which can be modulated pharmacologically.