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1.
Biochemistry (Mosc) ; 86(4): 389-396, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33941061

RESUMEN

The novel coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major public health emergency worldwide with over 118.27-million confirmed COVID-19 cases and 2.62-million deaths recorded, as of March 12, 2021. Although this disease primarily targets lungs, damages in other organs, such as heart, kidney, liver, and testis, may occur. Testis is the cornerstone of male reproduction, while reproductive health is the most valuable resource for continuity of the human race. Given the unique nature of SARS-CoV-2, the mechanisms of its impact on the testes have yet to be fully explored. Notably, coronaviruses have been found to invade target cells through the angiotensin-converting enzyme 2 receptor, which can be found in the respiratory, gastrointestinal, cardiovascular, urinary tract, and reproductive organs, such as testes. Coronavirus studies have suggested that testes might be a potential target for SARS-CoV-2 infection. The first etiopathogenic concept proposed by current hypotheses indicates that the virus can invade testes through the angiotensin-converting enzyme 2 receptor. Next, the activated inflammatory response in the testes, disease-associated fever, and COVID-19 medications might be implicated in testicular alterations. Although evidence regarding the presence of SARS-CoV-2 mRNA in semen remains controversial, this emphasizes the need for researchers to pay closer attention to sexually transmitted diseases and male fertility after recovering from COVID-19. In this review the latest updates regarding COVID-19-associated testicular dysfunction are summarized and possible pathogenic mechanisms are discussed.


Asunto(s)
/metabolismo , Fertilidad , Pandemias , Testículo/metabolismo , /mortalidad , Humanos , Masculino , Testículo/patología , Testículo/virología
2.
Int J Mol Sci ; 22(6)2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33809872

RESUMEN

The epigenetic mechanisms controlling germ cell development and differentiation are still not well understood. Sirtuin-1 (SIRT1) is a nicotinamide adenosine dinucleotide (NAD)-dependent histone deacetylase and belongs to the sirtuin family of deacetylases. It catalyzes the removal of acetyl groups from a number of protein substrates. Some studies reported a role of SIRT1 in the central and peripheral regulation of reproduction in various non-primate species. However, testicular SIRT1 expression and its possible role in the testis have not been analyzed in primates. Here, we document expression of SIRT1 in testes of different primates and some non-primate species. SIRT1 is expressed mainly in the cells of seminiferous tubules, particularly in germ cells. The majority of SIRT1-positive germ cells were in the meiotic and postmeiotic phase of differentiation. However, SIRT1 expression was also observed in selected premeiotic germ cells, i.e., spermatogonia. SIRT1 co-localized in spermatogonia with irisin, an endocrine factor specifically expressed in primate spermatogonia. In marmoset testicular explant cultures, SIRT1 transcript levels are upregulated by the addition of irisin as compared to untreated controls explants. Rhesus macaques are seasonal breeders with high testicular activity in winter and low testicular activity in summer. Of note, SIRT1 mRNA and SIRT1 protein expression are changed between nonbreeding (low spermatogenesis) and breeding (high spermatogenesis) season. Our data suggest that SIRT1 is a relevant factor for the regulation of spermatogenesis in primates. Further mechanistic studies are required to better understand the role of SIRT1 during spermatogenesis.


Asunto(s)
Regulación de la Expresión Génica , Sirtuina 1/genética , Testículo/metabolismo , Animales , Callithrix , Fibronectinas/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Inmunohistoquímica , Macaca mulatta , Masculino , Primates , Estaciones del Año , Sirtuina 1/metabolismo , Transcripción Genética
3.
Toxicol Appl Pharmacol ; 419: 115514, 2021 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-33798595

RESUMEN

Phthalates as plasticizers are widely used in many consumer products. Dipentyl phthalate (DPeP) is one of phthalates. However, there are currently few data on whether DPeP exposure affects rat Leydig cell development. In this study, we investigated the effects of in utero DPeP exposure on Leydig cell development in the testes of male newborn and adult rats. From gestational days 14 to 21, Sprague-Dawley pregnant rats were gavaged vehicle (corn oil, control) or DPeP (10, 50, 100, and 500 mg/kg body weight/day). Testosterone and the expression of Leydig cell genes and proteins in the testis at birth and at postnatal day 56 were examined. DPeP dose-dependently reduced serum testosterone levels of male offspring at birth and at postnatal day 56 at 100 and 500 mg/kg and lowered serum luteinizing hormone levels at adult males at ≥10 mg/kg when compared with the control. In addition, DPeP increased number of fetal Leydig cells by inducing their proliferation but down-regulated the expression of Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, and Insl3 in fetal Leydig cells per se. DPeP reduced number of adult Leydig cells by inducing cell apoptosis and down-regulated the expression of Lhcgr and Star in adult Leydig cells at postnatal day 56. DPeP lowered SIRT1 and BCL2 levels in the testis of adult rats. In conclusion, DPeP adversely affects both fetal and adult Leydig cell development after in utero exposure.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Intersticiales del Testículo/efectos de los fármacos , Ácidos Ftálicos/toxicidad , Plastificantes/toxicidad , Efectos Tardíos de la Exposición Prenatal , Testículo/efectos de los fármacos , Factores de Edad , Animales , Apoptosis/efectos de los fármacos , Femenino , Regulación del Desarrollo de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Edad Gestacional , Células Intersticiales del Testículo/metabolismo , Células Intersticiales del Testículo/patología , Hormona Luteinizante/sangre , Masculino , Exposición Materna , Embarazo , Ratas Sprague-Dawley , Testículo/embriología , Testículo/metabolismo , Testosterona/sangre
4.
Molecules ; 26(6)2021 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-33803601

RESUMEN

Hypogonadism, associated with low levels of testosterone synthesis, has been implicated in several diseases. Recently, the quest for natural alternatives to prevent and treat hypogonadism has gained increasing research interest. To this end, the present study explored the effect of S-allyl cysteine (SAC), a characteristic organosulfur compound in aged-garlic extract, on testosterone production. SAC was administered at 50 mg/kg body weight intraperitoneally into 7-week-old BALB/c male mice in a single-dose experiment. Plasma levels of testosterone and luteinizing hormone (LH) and testis levels of proteins involved in steroidogenesis were measured by enzymatic immunoassay and Western blot, respectively. In addition, mouse testis-derived I-10 cells were also used to investigate the effect of SAC on steroidogenesis. In the animal experiment, SAC significantly elevated testosterone levels in both the plasma and the testis without changing the LH level in plasma and increased phosphorylated protein kinase A (p-PKA) levels. Similar results were also observed in I-10 cells. The findings demonstrating the increasing effect of SAC on p-PKA and mRNA levels of Cyp11a suggest that SAC increases the testosterone level by activating the PKA pathway and could be a potential target for hypogonadism therapeutics.


Asunto(s)
Cisteína/análogos & derivados , Testículo/efectos de los fármacos , Testículo/metabolismo , Testosterona/biosíntesis , Animales , Línea Celular , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Cisteína/farmacología , Activación Enzimática/efectos de los fármacos , Ajo/química , Células Intersticiales del Testículo/efectos de los fármacos , Células Intersticiales del Testículo/metabolismo , Hormona Luteinizante/sangre , Masculino , Ratones , Ratones Endogámicos BALB C , Fosforilación , Testículo/citología , Testosterona/sangre
5.
Environ Pollut ; 278: 116835, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33706242

RESUMEN

Pendimethalin (PDM) is a dinitroaniline crop pesticide that is extensively utilized worldwide. However, the reproductive toxicity and cellular mechanisms of PDM have not been identified. Therefore, we elucidated the adverse effects of PDM on the reproductive system using mouse testicular Leydig and Sertoli cells (TM3 and TM4 cells, respectively). Our results demonstrated that PDM suppressed the viability and proliferation of TM3 and TM4 cells. Additionally, PDM induced cytosolic calcium upregulation and permeabilization of mitochondrial membrane potential in both TM3 and TM4 cells. We also verified that PDM activates the endoplasmic reticulum (ER) stress pathway and autophagy. Furthermore, we confirmed that activation of ER stress and autophagy were blocked by 2-aminoethoxydiphenyl borate (2-APB) treatment. Finally, we confirmed PDM-induced cell cycle arrest and apoptosis in TM3 and TM4 cells. Thus, we first demonstrated that PDM impedes the survival of testis cells, and further, their function.


Asunto(s)
Mitocondrias , Testículo , Compuestos de Anilina , Animales , Apoptosis , Autofagia , Estrés del Retículo Endoplásmico , Masculino , Ratones , Testículo/metabolismo
6.
Int J Mol Sci ; 22(4)2021 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-33669425

RESUMEN

Thanks to the analysis of an Interspecific Recombinant Congenic Strain (IRCS), we previously defined the Mafq1 quantitative trait locus as an interval on mouse Chromosome 1 associated with male hypofertility and ultrastructural abnormalities. We identified the Spermatogenesis associated protein 3 gene (Spata3 or Tsarg1) as a pertinent candidate within the Mafq1 locus and performed the CRISPR-Cas9 mediated complete deletion of the gene to investigate its function. Male mice deleted for Spata3 were normally fertile in vivo but exhibited a drastic reduction of efficiency in in vitro fertilization assays. Mobility parameters were normal but ultrastructural analyses revealed acrosome defects and an overabundance of lipids droplets in cytoplasmic remnants. The deletion of the Spata3 gene reproduces therefore partially the phenotype of the hypofertile IRCS strain.


Asunto(s)
Acrosoma/patología , Fertilización In Vitro/métodos , Eliminación de Gen , Infertilidad Masculina/genética , Proteínas/genética , Acrosoma/metabolismo , Acrosoma/ultraestructura , Animales , Sistemas CRISPR-Cas , Modelos Animales de Enfermedad , Femenino , Infertilidad Masculina/metabolismo , Gotas Lipídicas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fenotipo , Embarazo , Proteínas/metabolismo , Motilidad Espermática/genética , Espermatogénesis/genética , Testículo/metabolismo
7.
Artículo en Inglés | MEDLINE | ID: mdl-33670275

RESUMEN

Advancement in the field of nanotechnology has prompted the need to elucidate the deleterious effects of nanoparticles (NPs) on reproductive health. Many studies have reported on the health safety issues related to NPs by investigating their exposure routes, deposition and toxic effects on different primary and secondary organs but few studies have focused on NPs' deposition in reproductive organs. Noteworthy, even fewer studies have dealt with the toxic effects of NPs on reproductive indices and sperm parameters (such as sperm number, motility and morphology) by evaluating, for instance, the histopathology of seminiferous tubules and testosterone levels. To date, the research suggests that NPs can easily cross the blood testes barrier and, after accumulation in the testis, induce adverse effects on spermatogenesis. This review aims to summarize the available literature on the risks induced by NPs on the male reproductive system.


Asunto(s)
Infertilidad Masculina , Nanopartículas , Humanos , Infertilidad Masculina/inducido químicamente , Masculino , Nanopartículas/toxicidad , Estrés Oxidativo , Recuento de Espermatozoides , Motilidad Espermática , Espermatogénesis , Espermatozoides/metabolismo , Testículo/metabolismo , Testosterona/metabolismo
8.
Environ Toxicol ; 36(6): 1206-1216, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33683001

RESUMEN

Perfluorotridecanoic acid (PFTrDA) is a long-chain perfluoroalkyl substance, and its effect on the differentiation of fetal Leydig cells remains unclear. The objective of this study is to explore the effect of in utero PFTrDA exposure on the differentiation of fetal Leydig cells and investigate its underlying mechanisms. Pregnant Sprague-Dawley female rats were daily administered by gavage of PFTrDA at doses of 0, 1, 5, and 10 mg/kg from gestational day 14 to 21. PFTrDA had no effect on the body weight of dams, but significantly reduced the body weight and anogenital distance of male pups at birth at a dose of 10 mg/kg. PFTrDA significantly decreased serum testosterone levels as low as 1 mg/kg. PFTrDA did not affect fetal Leydig cell number, but promoted abnormal aggregation of fetal Leydig cells at doses of 5 and 10 mg/kg. PFTrDA down-regulated the expression of Insl3, Lhcgr, Scarb1, Star, Hsd3b1, Cyp17a1, Nr5a1, and Dhh as well as their proteins. PFTrDA lowered the levels of antioxidants (SOD1, CAT, and GPX1), induced autophagy as shown by increased levels of LC3II and beclin1, and reduced the phosphorylation of mTOR. In conclusion, PFTrDA inhibits the differentiation of fetal Leydig cells in male pups after in utero exposure mainly through increasing oxidative stress and inducing autophagy.


Asunto(s)
Testículo , Testosterona , Animales , Autofagia , Diferenciación Celular , Femenino , Células Intersticiales del Testículo/metabolismo , Masculino , Estrés Oxidativo , Embarazo , Ratas , Ratas Sprague-Dawley , Testículo/metabolismo , Testosterona/metabolismo
9.
Int J Mol Sci ; 22(5)2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33652607

RESUMEN

Spermatogenesis is a complex process, in which spermatogonial cells proliferate and differentiate in the seminiferous tubules of the testis to generate sperm. This process is under the regulation of endocrine and testicular paracrine/autocrine factors. In the present study, we demonstrated that colony stimulating factor-1 (CSF-1) is produced by mouse testicular macrophages, Leydig, Sertoli, peritubular cells and spermatogonial cells (such as CDH1-positively stained cells; a marker of spermatogonial cells). In addition, we demonstrated the presence of CSF-1 and its receptor (CSF-1R) in testicular macrophages, Leydig, Sertoli, peritubular cells and spermatogonial cells of human testis. We also show that the protein levels of CSF-1 were the highest in testis of 1-week-old mice and significantly decreased with age (2-12-week-old). However, the transcriptome levels of CSF-1 significantly increased in 2-3-week-old compared to 1-week-old, and thereafter significantly decreased with age. On the other hand, the transcriptome levels of CSF-1R was significantly higher in mouse testicular tissue of all examined ages (2-12-week-old) compared to 1-week-old. Our results demonstrate the involvement of CSF-1 in the induction the proliferation and differentiation of spermatogonial cells to meiotic and postmeiotic stages (BOULE- and ACROSIN-positive cells) under in vitro culture conditions, using methylcellulose culture system (MCS). Thus, it is possible to suggest that CSF-1 system, as a testicular paracrine/autocrine system, is involved in the development of different stages of spermatogenesis and may be used in the development of future therapeutic strategies for treatment of male infertility.


Asunto(s)
Factor Estimulante de Colonias de Macrófagos/metabolismo , Espermatogénesis , Testículo/metabolismo , Animales , Humanos , Masculino , Ratones , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Testículo/citología
10.
Ecotoxicol Environ Saf ; 214: 112121, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33721578

RESUMEN

Perfluorooctane sulfonate is related to male reproductive dysfunction in rats and humans. However, the underlying mechanism remains unknown. Here, we reported the effects of short-term exposure to perfluorooctane sulfonate on the regeneration of Leydig cells in vivo and investigated possible mechanisms in vitro. After adult male Sprague-Dawley rats were gavaged perfluorooctane sulfonate (0, 5 or 10 mg/kg/day) for 7 days and then injected intraperitoneally ethane dimethane sulfonate next day to eliminate Leydig cells, the Leydig cell regeneration process was monitored. Perfluorooctane sulfonate significantly lowered serum testosterone levels, reduced the number of regenerated Leydig cells, down-regulated the expression of Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, and Dhh) and their proteins at doses of 5 and 10 mg/kg 35 and 56 days after ethane dimethane sulfonate. Using a 3D seminiferous tubule culture system to study the development of stem Leydig cells, we found that perfluorooctane sulfonate inhibited stem Leydig cell proliferation and differentiation and hedgehog signaling pathway. In conclusion, a short-term exposure to perfluorooctane sulfonate can inhibit the development of stem Leydig cells into the Leydig cell lineage via direct suppression of hedgehog signaling pathway and indirect inhibition of desert hedgehog section by Sertoli cells.


Asunto(s)
Ácidos Alcanesulfónicos/toxicidad , Fluorocarburos/toxicidad , Testículo/efectos de los fármacos , Animales , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Proteínas Hedgehog/metabolismo , Masculino , Mesilatos , Ratas Sprague-Dawley , Regeneración , Transducción de Señal/efectos de los fármacos , Testículo/citología , Testículo/metabolismo , Testículo/fisiología , Testosterona/sangre
11.
Arch Insect Biochem Physiol ; 106(4): e21779, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33660341

RESUMEN

Shrub (CG8055) encodes the vps32/snf7 protein, a filament-forming subunit of the ESCRT (endosomal sorting complexes required for transport)-III complex involved in inward membrane budding. It was reported that shrub was required for abscission in female germline stem cells. In this study, we showed that the expression level of shrub in the testis was significantly higher than that in the ovary of 1-day-old Drosophila melanogaster, suggesting a role in male reproduction. Then we used nosGal4 driver to knockdown shrub specifically in the fly testis and found that this resulted in a significantly lower paternal effect egg hatch rate relative to the control group. Immunofluorescence staining showed that shrub knockdown in fly testes caused an accumulation of early-stage germ cells and lack of spectrin caps. In the late stages (spermiogenesis), the control testis contained multiple compacted spermatid bundles and individualization complexes (ICs) consisting of actin cones, whereas there were scattered spermatid nuclei and only a few ICs with disorganized actin cones in the shrub knockdown testis. Finally, the control seminal vesicle was full of mature sperms with needle-like heads, but in shrub knockdown testis 75% of seminal vesicles had no mature sperms. We also found that knockdown of shrub in fly testes led to upregulated expression of several cytoskeleton-associated genes, and an accumulation of ubiquitylated proteins. These results suggest that knockdown of shrub in fly testes might damage spermatogenesis by affecting transportability.


Asunto(s)
Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Proteínas del Tejido Nervioso/metabolismo , Espermatogénesis/fisiología , Animales , Drosophila melanogaster/metabolismo , Drosophila melanogaster/fisiología , Femenino , Masculino , Ovario/metabolismo , Testículo/metabolismo
12.
Cell Prolif ; 54(5): e13000, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33666296

RESUMEN

OBJECTIVES: Mammalian spermatogenesis is a biological process of male gamete formation. Gonocytes are the only precursors of spermatogonial stem cells (SSCs) which develop into mature spermatozoa. DDX5 is one of DEAD-box RNA helicases and expresses in male germ cells, suggesting that Ddx5 plays important functions during spermatogenesis. Here, we explore the functions of Ddx5 in regulating the specification of gonocytes. MATERIALS AND METHODS: Germ cell-specific Ddx5 knockout (Ddx5-/- ) mice were generated. The morphology of testes and epididymides and fertility in both wild-type and Ddx5-/- mice were analysed. Single-cell RNA sequencing (scRNA-seq) was used to profile the transcriptome in testes from wild-type and Ddx5-/- mice at postnatal day (P) 2. Dysregulated genes were validated by single-cell qRT-PCR and immunofluorescent staining. RESULTS: In male mice, Ddx5 was expressed in germ cells at different stages of development. Germ cell-specific Ddx5 knockout adult male mice were sterile due to completely devoid of germ cells. Male germ cells gradually disappeared in Ddx5-/- mice from E18.5 to P6. Single-cell transcriptome analysis showed that genes involved in cell cycle and glial cell line-derived neurotrophic factor (GDNF) pathway were significantly decreased in Ddx5-deficient gonocytes. Notably, Ddx5 ablation impeded the proliferation of gonocytes. CONCLUSIONS: Our study reveals the critical roles of Ddx5 in fate determination of gonocytes, offering a novel insight into the pathogenesis of male sterility.


Asunto(s)
ARN Helicasas DEAD-box/metabolismo , Células Germinativas/metabolismo , Animales , Animales Recién Nacidos , ARN Helicasas DEAD-box/genética , Regulación del Desarrollo de la Expresión Génica , Genotipo , Células Germinativas/citología , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Infertilidad/metabolismo , Infertilidad/patología , Masculino , Ratones , Ratones Noqueados , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Testículo/metabolismo , Testículo/patología
13.
Toxicol Appl Pharmacol ; 418: 115510, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33775663

RESUMEN

Prevention or repair of DNA damage is critical to inhibit carcinogenesis in living organisms. Using quantitative RT2 Profiler™ PCR array, we investigated if trans-resveratrol could modulate the transcription of DNA damage sensing/repair pathway genes in euglycemic and non-obese type 2 diabetic Goto-Kakizaki rat testis. Trans-resveratrol imparted disparate effects on gene expressions. In euglycemic rats, it downregulated 79% and upregulated 2% of genes. However, in diabetic rats, it upregulated only 2% and downregulated 4% of genes. As such, diabetes upregulated 16% and downregulated 4% of genes. Trans-resveratrol normalized the expression of 9 (60%) out of 15 upregulated genes in diabetic rats. In euglycemic rats, trans-resveratrol inhibited ATM/ATR, DNA damage repair, pro-cell cycle progression, and apoptosis signaling genes. However, it increased Cdkn1a and Sumo1, indicating cell cycle arrest, apoptosis, and cytostasis in conjunction with increased DNA double-strand breaks and apoptosis. Diabetes increased DNA damage and apoptosis but did not affect ATM/ATR and double-strand break repair genes, although it increased few single-strand repair genes. Diabetes increased Abl1 and Sirt1, which may be related to apoptosis, but their increase may well suggest the enhanced cell cycle progression and putative carcinogenicity. The transcription of Rad17 and Smc1a increased in diabetic rats indicating G2 phase arrest and increases in a few DNA single-strand breaks repair genes suggesting DNA damage repair. Trans-resveratrol inhibits the cell cycle and causes cell death in euglycemic rat testis but normalizes diabetes-induced genes related to DNA damage and cell cycle control, suggesting its usefulness in maintaining DNA integrity in diabetes.


Asunto(s)
Glucemia/metabolismo , Daño del ADN , Reparación del ADN , Diabetes Mellitus Tipo 2/sangre , Resveratrol/toxicidad , Testículo/efectos de los fármacos , Transcripción Genética/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Biomarcadores/sangre , Puntos de Control del Ciclo Celular , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Masculino , Ratas Wistar , Testículo/metabolismo , Testículo/patología
14.
Mol Med Rep ; 23(5)2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33760102

RESUMEN

Gene expression analyses have revealed that there are >2,300 testis-enriched genes in mice, and gene knockout models have shown that a number of them are responsible for male fertility. However, the functions of numerous genes have yet to be clarified. The aim of the present study was to identify the expression pattern of testis-expressed protein 33 (TEX33) in mice and explore the role of TEX33 in male reproduction. Reverse transcription-polymerase chain reaction and western blot assays were used to investigate the mRNA and protein levels of TEX33 in mouse testes during the first wave of spermatogenesis. Immunofluorescence analysis was also performed to identify the cellular and structural localization of TEX33 protein in the testes. Tex33 knockout mice were generated by CRISPR/Cas9 gene-editing. Histological analysis with hematoxylin and eosin or periodic acid-Schiff (PAS) staining, computer-assisted sperm analysis (CASA) and fertility testing, were also carried out to evaluate the effect of TEX33 on mouse spermiogenesis and male reproduction. The results showed that Tex33 mRNA and protein were exclusively expressed in mouse testes and were first detected on postnatal days 21-28 (spermiogenesis phase); their expression then remained into adulthood. Immunofluorescence analysis revealed that TEX33 protein was located in the spermatids and sperm within the seminiferous tubules of the mouse testes, and exhibited specific localization to the acrosome, flagellum and manchette during spermiogenesis. These results suggested that TEX33 may play a role in mouse spermiogenesis. However, Tex33 knockout mice presented no detectable difference in testis-to-body weight ratios when compared with wild-type mice. PAS staining and CASA revealed that spermatogenesis and sperm quality were normal in mice lacking Tex33. In addition, fertility testing suggested that the Tex33 knockout mice had normal reproductive functions. In summary, the findings of the present study indicate that TEX33 is associated with spermiogenesis but is not essential for sperm development and male fertility.


Asunto(s)
Fertilidad/genética , Infertilidad Masculina/genética , Espermatogénesis/genética , Testículo/metabolismo , Acrosoma/metabolismo , Acrosoma/patología , Animales , Regulación del Desarrollo de la Expresión Génica/genética , Humanos , Infertilidad Masculina/patología , Masculino , Ratones , Ratones Noqueados , Espermatozoides/crecimiento & desarrollo , Espermatozoides/patología , Testículo/patología
15.
Nat Commun ; 12(1): 1361, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33649327

RESUMEN

Sperm contributes diverse RNAs to the zygote. While sperm small RNAs have been shown to impact offspring phenotypes, our knowledge of the sperm transcriptome, especially the composition of long RNAs, has been limited by the lack of sensitive, high-throughput experimental techniques that can distinguish intact RNAs from fragmented RNAs, known to abound in sperm. Here, we integrate single-molecule long-read sequencing with short-read sequencing to detect sperm intact RNAs (spiRNAs). We identify 3440 spiRNA species in mice and 4100 in humans. The spiRNA profile consists of both mRNAs and long non-coding RNAs, is evolutionarily conserved between mice and humans, and displays an enrichment in mRNAs encoding for ribosome. In sum, we characterize the landscape of intact long RNAs in sperm, paving the way for future studies on their biogenesis and functions. Our experimental and bioinformatics approaches can be applied to other tissues and organisms to detect intact transcripts.


Asunto(s)
Secuencia Conservada/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , ARN/genética , Imagen Individual de Molécula , Espermatozoides/metabolismo , Animales , Evolución Molecular , Ontología de Genes , Humanos , Masculino , Ratones Endogámicos C57BL , ARN/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ribosomas/metabolismo , Testículo/metabolismo , Transcriptoma/genética
16.
Sci Total Environ ; 770: 144727, 2021 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-33736362

RESUMEN

Melamine poisoning incidents and potential health risks raise global attention. Recent studies imply that melamine exposure is related to male reproductive dysfunction, however, the underlying mechanisms are unclear. In this study, 32 male Kunming mice were administered with 0, 12.5, 25, and 50 mg/L melamine via drinking water for 13 weeks, respectively. Sperm quality, testicular morphology, and the mRNA expression levels of MAPK family members p38, ERK5, ERK1/2, JNK1/2/3 and their downstream transcription factors GADD153, MAX, MEF2C, CREB, c-Myc, JunD, c-JUN, Sap1a, p53, ATF-2, Elk1, and Nur77 in testes were investigated. The results revealed that low-dose melamine exposure reduced sperm quality, altered the testicular histological structure, and reduced the mRNA expression levels of p38, ERK1/2, MAX and Sap1a in the testes. The p38 and phosphorylated-p38 expressions analysis further suggested that the down-regulated phosphorylation of p38 and downstream transcription factors MAX and Sap1a play key roles in male reproductive dysfunction caused by melamine. Altogether, our study provides a new insight to elucidate the underlying mechanisms by which melamine induces male reproductive toxicity, and to evaluate the health risks of melamine.


Asunto(s)
Testículo , Factores de Transcripción , Animales , Masculino , Ratones , Fosforilación , Testículo/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Triazinas/metabolismo , Triazinas/toxicidad
17.
Environ Health Prev Med ; 26(1): 31, 2021 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-33678156

RESUMEN

BACKGROUND: The industrial revolution has resulted in increased synthesis and the introduction of a variety of compounds into the environment and their potentially hazardous effects have been observed in the biota. The present study was aimed to evaluate the potential endocrine-disrupting effects of chronic exposure to the low concentrations of bisphenol S (BPS) in male rats. METHODS: Weaning male Sprague-Dawley rats (22 days old) were either exposed to water containing 0.1% ethanol for control or different concentrations of BPS (0.5, 5, and 50 µg/L) in drinking water for 48 weeks in the chronic exposure study. After completion of the experimental period, animals were dissected and different parameters (hormone concentrations, histology of testis and epididymis, oxidative stress and level of antioxidant enzymes in the testis, daily sperm production (DSP), and sperm parameters) were determined. RESULTS: Results of the present study showed a significant alteration in the gonadosomatic index (GSI) and relative reproductive organ weights. Oxidative stress in the testis was significantly elevated while sperm motility, daily sperm production, and the number of sperm in epididymis were reduced. Plasma testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) concentrations were reduced and estradiol levels were high in the 50 µg/L-exposed group. Histological observations involved a significant reduction in the epithelial height of the testis along with disrupted spermatogenesis, an empty lumen of the seminiferous tubules, and the caput region of the epididymis. CONCLUSION: These results suggest that exposure to 5 and 50 µg/L of BPS for the chronic duration started from an early age can induce structural changes in testicular tissue architecture and endocrine alterations in the male reproductive system which may lead to infertility in males.


Asunto(s)
Disruptores Endocrinos/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Ambientales/toxicidad , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Infertilidad Masculina/inducido químicamente , Fenoles/toxicidad , Sulfonas/toxicidad , Testículo/efectos de los fármacos , Animales , Biomarcadores , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiopatología , Infertilidad Masculina/metabolismo , Infertilidad Masculina/fisiopatología , Masculino , Ratas , Ratas Sprague-Dawley , Testículo/metabolismo , Testículo/fisiopatología , Pruebas de Toxicidad Crónica
18.
Pestic Biochem Physiol ; 173: 104773, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33771252

RESUMEN

Flufenoxuron is a benzoylurea pesticide that is used to eradicate insects and acarids in the farmland. Even though it specifically works on target animals, the possibilities of its bioaccumulation and harmful effects on non-target animals cannot be denied. As the usage and application of pesticides increases, exposure to them also increases through ingestion of food residues, inhalation, or dermal contact. Pesticides could also be considered as endocrine disruptor chemicals; however, the reproductive toxicity and cellular mechanisms of flufenoxuron have not been identified. Our results indicate that flufenoxuron inhibits cellular proliferation and hampers calcium homeostasis, especially by targeting mitochondria. We also confirmed the induction of endoplasmic reticulum (ER) stress and ER-mitochondrial contact signaling. Using pharmacological inhibitors, we also observed that the mitogen-activated protein kinase and Akt signaling pathways were upregulated by flufenoxuron. Further, by oral administration of flufenoxuron (100 mg/kg/bw) to C57BL/6 male mice, we observed transcriptional changes in the testis-related genes. Collectively, we demonstrated that flufenoxuron inhibits cell proliferation and alters gene expression in mouse testis cells and induces testicular dysfunction in mice. These results indicate that flufenoxuron may be harmful to male reproduction and fertility in the early stages of pregnancy.


Asunto(s)
Mitocondrias , Testículo , Animales , Apoptosis , Proliferación Celular , Masculino , Ratones , Ratones Endogámicos C57BL , Compuestos de Fenilurea , Testículo/metabolismo
19.
Arch Insect Biochem Physiol ; 106(3): e21765, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33590535

RESUMEN

Sphingolipids are ubiquitous structural components of eukaryotic cell membranes which are vital for maintaining the integrity of cells. Alkaline ceramidase is a key enzyme in sphingolipid biosynthesis pathway; however, little is known about the role of the enzyme in the male reproductive system of Drosophila melanogaster. To investigate the impact of alkaline ceramidase (Dacer) on male Drosophila, we got Dacer deficiency mutants (MUs) and found they displayed apparent defects in the testis's phenotype. To profile the molecular changes associated with this abnormal phenotype, we performed de novo transcriptome analyses of the MU and wildtype (WT) testes; and revealed 1239 upregulated genes and 1102 downregulated genes. Then, six upregulated DEGs (papilin [Ppn], croquemort [Crq], terribly reduced optic lobes [Trol], Laminin, Wunen-2, collagen type IV alpha 1 [Cg25C]) and three downregulated DEGs (mucin related 18B [Mur18B], rhomboid-7 [Rho-7], CG3168) were confirmed through quantitative real-time polymerase chain reaction in WT and MU samples. The differentially expressed genes were mainly associated with catalytic activity, oxidoreductase activity and transmembrane transporter activity, which significantly contributed to extracellular matrix-receptor interaction, fatty acids biosynthesis as well as glycine, serine, and threonine metabolism. The results highlight the importance of Dacer in the reproductive system of D. melanogaster and provide valuable resources to dig out the specific biological functions of Dacer in insect reproduction.


Asunto(s)
Ceramidasa Alcalina/genética , Drosophila melanogaster/genética , Testículo/metabolismo , Ceramidasa Alcalina/metabolismo , Animales , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Expresión Génica , Perfilación de la Expresión Génica , Genes de Insecto , Masculino , Mutación , Receptores de Superficie Celular/metabolismo , Reproducción , Esfingolípidos/metabolismo , Testículo/patología
20.
Life Sci ; 271: 119179, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33577849

RESUMEN

BACKGROUND: Male infertility and reproductive dysfunctions have become major global health problems. Although several causative factors have been attributed to this challenge, of importance are alterations in maternal-foetal environment, diet-induced transcriptional changes and dysregulation in chemical signaling via hypothalamic-gonadal axis. AIM: The present study investigated the impact of maternal high-fat diet (HFD) consumption and the putative role of Quercetin-3-O-rutinoside on reproductive functions of male offspring rats at critical developmental stages with a quest to unravel the underpinned molecular changes. MATERIALS AND METHODS: Fifty-six pregnant rats (previously fed normal diet ND) or 45% HFD) were maintained on supplemented chow (150 mg/kg QR) - ND/QR, HFD/QR throughout gestation. Subsequently, dams (n = 7) and offspring (n = 6) were sacrificed at post-natal day (PND) 21, 28 and 35, respectively, and the blood, placenta, hypothalamus (HT), and testicular samples were processed for molecular analysis of Gonadotropin-releasing hormone (GnRH), Luteinizing hormone (LH), testosterone, chemerin, chemokine-like receptor 1 (CMKLR1), tumour necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and nuclear factor kappa B (NF-κB). KEY FINDINGS: We observed a significant decrease in GnRH level in the HFD group at PND21 and PND28 in male offspring and treatment with QR significantly reduced GnRH. There was a significant reduction in LH levels in the HFD group at PND 21 in the male offspring accompanied by a significant decrease in testosterone level at PND 28 and PND35 which appears to be age dependent. In the HT, Chemerin and CMKLR1 was significantly upregulated in the HFD group at PND 21 and PND 35 respectively while CMKLR1 was significantly downregulated in the HFD group of the placenta and testis at PND 21. TNF-α, IL-1ß and NF-κB were also expressed in the placenta, HT and testis at PND 21. SIGNIFICANCE: Male fertility is affected by maternal HFD consumption while chemerin, CMKLR1 and TNF-α, may play a significant role in male steroidogenesis. Treatment with QR had little or no ameliorative effect on HFD induced alterations in male reproductive functions.


Asunto(s)
Dieta Alta en Grasa/efectos adversos , Glucósidos/farmacología , Fenómenos Fisiologicos Nutricionales Maternos/fisiología , Efectos Tardíos de la Exposición Prenatal/metabolismo , Quercetina/análogos & derivados , Reproducción/fisiología , Testículo/metabolismo , Animales , Femenino , Hormona Liberadora de Gonadotropina/metabolismo , Masculino , Fenómenos Fisiologicos Nutricionales Maternos/efectos de los fármacos , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Quercetina/farmacología , Ratas , Ratas Sprague-Dawley , Reproducción/efectos de los fármacos , Testículo/efectos de los fármacos , Testosterona/metabolismo
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