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1.
Nat Commun ; 12(1): 3184, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34075040

RESUMO

During spermatogenesis, meiosis is accompanied by a robust alteration in gene expression and chromatin status. However, it remains elusive how the meiotic transcriptional program is established to ensure completion of meiotic prophase. Here, we identify a protein complex that consists of germ-cell-specific zinc-finger protein ZFP541 and its interactor KCTD19 as the key transcriptional regulators in mouse meiotic prophase progression. Our genetic study shows that ZFP541 and KCTD19 are co-expressed from pachytene onward and play an essential role in the completion of the meiotic prophase program in the testis. Furthermore, our ChIP-seq and transcriptome analyses identify that ZFP541 binds to and suppresses a broad range of genes whose function is associated with biological processes of transcriptional regulation and covalent chromatin modification. The present study demonstrates that a germ-cell specific complex that contains ZFP541 and KCTD19 promotes the progression of meiotic prophase towards completion in male mice, and triggers the reconstruction of the transcriptional network and chromatin organization leading to post-meiotic development.


Assuntos
Proteínas Cromossômicas não Histona/metabolismo , Estágio Paquíteno/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Espermátides/citologia , Espermatogênese/genética , Fatores de Transcrição/metabolismo , Animais , Sequenciamento de Cromatina por Imunoprecipitação , Proteínas Cromossômicas não Histona/genética , Modelos Animais de Doenças , Feminino , Histona Desacetilase 1/metabolismo , Histona Desacetilase 2/metabolismo , Humanos , Infertilidade Masculina/genética , Masculino , Camundongos , Camundongos Knockout , Oócitos/citologia , Oócitos/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , RNA-Seq , Espermátides/metabolismo , Fatores de Transcrição/genética , Transcrição Genética
2.
An Acad Bras Cienc ; 93(2): e20190557, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34105611

RESUMO

The reproduction of monogamous wild birds in captivity it`s difficult and the apparent low fertility in males requires more investigations. The objective of the study was to test the hypothesis that wild bird species in captivity would present low reproductive potential, through the analysis of the morphological characteristics of Ara ararauna testicles, maintained in captivity, correlating them with the climate variations in the Cerrado Biome. For that, testicles were captured in April (dry) and October (rainy). The right and left testicles showed mean weight, gonadosomatic index, longer axis, and volume similar between the dry and rainy season. Only the shorter axis demonstrated higher values during the rainy season. The morphometric variables of the seminiferous tubules have also higher values during the rainy season. By these histological and morphometric characteristics of the seminiferous epithelium we can conclude that, during the rainy season, the testicles were in gonadal recrudescence, which precedes the reproduction phase. During the dry season, the testicles were in the rest phase of the seminiferous epithelium. Therefore, we concluded that the species in captivity, under Cerrado environmental conditions, have kept their reproductive potential, presenting a complete spermatogenic cycle during the rainy season, which can guarantee the species perpetuation.


Assuntos
Túbulos Seminíferos , Testículo , Masculino , Reprodução , Estações do Ano , Espermatogênese
3.
Int J Mol Sci ; 22(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946947

RESUMO

The cation channel TRPV2 is known to be expressed by murine macrophages and is crucially involved in their functionality. Macrophages are frequent cells of the mouse testis, an immune-privileged and steroid-producing organ. TRPV2 expression by testicular macrophages and possible changes associated with age or inflammation have not been investigated yet. Therefore, we studied testes of young adult and old wild-type (WT) and AROM+ mice, i.e., transgenic mice overexpressing aromatase. In these animals, inflammatory changes are described in the testis, involving active macrophages, which increase with age. This is associated with impaired spermatogenesis and therefore AROM+ mice are a model for male infertility associated with sterile inflammation. In WT animals, testicular TRPV2 expression was mapped to interstitial CD206+ and peritubular MHC II+ macrophages, with higher levels in CD206+ cells. Expression levels of TRPV2 and most macrophage markers did not increase significantly in old mice, with the exception of CD206. As the number of TRPV2+ testicular macrophages was relatively small, their possible involvement in testicular functions and in aging in WT mice remains to be further studied. In AROM+ testis, TRPV2 was readily detected and levels increased significantly with age, together with macrophage markers and TNF-α. TRPV2 co-localized with F4/80 in macrophages and further studies showed that TRPV2 is mainly expressed by unusual CD206+MHC II+ macrophages, arising in the testis of these animals. Rescue experiments (aromatase inhibitor treatment and crossing with ERαKO mice) restored the testicular phenotype and also abolished the elevated expression of TRPV2, macrophage and inflammation markers. This suggests that TRPV2+ macrophages of the testis are part of an inflammatory cascade initiated by an altered sex hormone balance in AROM+ mice. The changes in testis are distinct from the described alterations in other organs of AROM+, such as prostate and spleen. When we monitored TRPV2 levels in another immune-privileged organ, namely the brain, we found that levels of TRPV2 were not elevated in AROM+ and remained stable during aging. In the adrenal, which similar to the testis produces steroids, we found slight, albeit not significant increases in TRPV2 in both AROM+ and WT mice, which were associated with age. Thus, the changes in the testis are specific for this organ.


Assuntos
Canais de Cálcio/fisiologia , Macrófagos/metabolismo , Orquite/metabolismo , Canais de Cátion TRPV/fisiologia , Testículo/metabolismo , Glândulas Suprarrenais/metabolismo , Fatores Etários , Animais , Aromatase/genética , Encéfalo/metabolismo , Canais de Cálcio/biossíntese , Canais de Cálcio/genética , Modelos Animais de Doenças , Genótipo , Infertilidade Masculina/metabolismo , Lectinas Tipo C/análise , Masculino , Lectinas de Ligação a Manose/análise , Camundongos , Camundongos Transgênicos , NADPH Oxidase 2/biossíntese , NADPH Oxidase 2/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores de Superfície Celular/análise , Espermatogênese , Canais de Cátion TRPV/biossíntese , Canais de Cátion TRPV/genética , Fator de Necrose Tumoral alfa/biossíntese
4.
Yi Chuan ; 43(5): 473-486, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-33972217

RESUMO

About 15% couples suffer from infertility, half of which are caused by male factors. Male infertility usually manifests as teratozoospermia, oligospermia and/or asthenospermia, of which the most severe form is azoospermia. In this review, we summarize the recent progress in the study of genetic factors involved in nonobstructive azoospermia and teratozoospermia, Recently, with the rapid development of high-throughput chips and sequencing technologies, many genetic factors of spermatogenesis have been discovered and analyzed. For the nonobstructive azoospermia, genome-wide association studies (GWAS) and high-throughput sequencing revealed many risk loci of nonobstructive azoospermia. For the teratozoospermia, the application of whole-exome sequencing (WES) revealed a series of disease-causing genes, greatly enriching our knowledge of teratozoospermia including multiple morphological abnormalities of the flagella (MMAF). The discovery of lots of disease genes helped the characterization of the pathological mechanisms of male infertility. Therefore, a comprehensive and in-depth understanding of genetic factors in spermatogenesis abnormalities will play important roles in the clinical diagnosis, treatment and genetic counseling of male infertility.


Assuntos
Azoospermia , Infertilidade Masculina , Azoospermia/genética , Estudo de Associação Genômica Ampla , Humanos , Infertilidade Masculina/genética , Masculino , Mutação , Espermatogênese/genética
5.
Zool Res ; 42(4): 401-405, 2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34047080

RESUMO

Single-cell RNA sequencing (scRNA-seq) is useful for exploring cell heterogeneity. For large animals, however, little is known regarding spermatogonial stem cell (SSC) self-renewal regulation, especially in dairy goats. In this study, we described a high-resolution scRNA-seq atlas derived from a dairy goat. We identified six somatic cell and five spermatogenic cell subtypes. During spermatogenesis, genes with significantly changed expression were mainly enriched in the Notch, TGF-ß, and Hippo signaling pathways as well as the signaling pathway involved in the regulation of stem cell pluripotency. We detected and screened specific candidate marker genes ( TKTL1 and AES) for spermatogonia. Our study provides new insights into goat spermatogenesis and the development of testicular somatic cells.


Assuntos
Cabras/genética , Análise de Sequência de RNA/veterinária , Análise de Célula Única , Testículo/citologia , Animais , Cabras/anatomia & histologia , Masculino , Análise de Sequência de RNA/métodos , Espermatogênese/genética
6.
Res Vet Sci ; 136: 495-502, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33857769

RESUMO

Mammalian semen is a physiological fluid composed of a cellular fraction (spermatozoa), and a liquid fraction (seminal plasma). Once delivered to the female genital tract, spermatozoa should be able to capacitate; a process which involves a plethora of biochemical and physiological changes required to fertilize the oocyte. Sperm production (spermatogenesis) occurs in the testes, whereby pluripotent spermatogonia differentiate to form the most morphologically specialized cells in the body. Further maturation of spermatozoa occurs in the epididymis, where they are stored prior to ejaculation. During this whole process, spermatozoa are exposed to different environments and cellular processes which may expose them to substantial levels of oxidative stress. To avoid damage associated with the unchecked production of reactive oxygen species (ROS), both spermatozoa, and the parts of the male genital tract in which they reside, are furnished with a suite of antioxidant molecules which are able to provide protection to these cells, thereby increasing their chance of being able to fertilize the oocyte and deliver an intact paternal genome to the future offspring. However, there are a host of reasons why these antioxidant systems may fail, including nutritional deficiencies, genetics, and disease states, and in these situations, a reduction or abolition of fertilizing capacity may result. This review paper focuses on the endogenous antioxidant defences available to spermatozoa during spermatogenesis and sperm maturation, the site of their production and their physiological role. Furthermore, we revised the causes and effects of antioxidant deficiencies (congenital or acquired during the animal's adulthood) on reproductive function in different animal species.


Assuntos
Antioxidantes/fisiologia , Fertilidade/fisiologia , Espermatozoides/fisiologia , Animais , Humanos , Masculino , Espécies Reativas de Oxigênio/metabolismo , Maturação do Esperma/fisiologia , Espermatogênese/fisiologia
7.
Front Med ; 15(2): 302-312, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33855678

RESUMO

Cullin-RING E3 ubiquitin ligase (CRL)-4 is a member of the large CRL family in eukaryotes. It plays important roles in a wide range of cellular processes, organismal development, and physiological and pathological conditions. DDB1- and CUL4-associated factor 8 (DCAF8) is a WD40 repeat-containing protein, which serves as a substrate receptor for CRL4. The physiological role of DCAF8 is unknown. In this study, we constructed Dcaf8 knockout mice. Homozygous mice were viable with no noticeable abnormalities. However, the fertility of Dcaf8-deficient male mice was markedly impaired, consistent with the high expression of DCAF8 in adult mouse testis. Sperm movement characteristics, including progressive motility, path velocity, progressive velocity, and track speed, were significantly lower in Dcaf8 knockout mice than in wild-type (WT) mice. However, the total motility was similar between WT and Dcaf8 knockout sperm. More than 40% of spermatids in Dcaf8 knockout mice showed pronounced morphological abnormalities with typical bent head malformation. The acrosome and nucleus of Dcaf8 knockout sperm looked similar to those of WT sperm. In vitro tests showed that the fertilization rate of Dcaf8 knockout mice was significantly reduced. The results demonstrated that DCAF8 plays a critical role in spermatogenesis, and DCAF8 is a key component of CRL4 function in the reproductive system.


Assuntos
Fator VIII , Espermatogênese , Animais , Proteínas Culina/genética , Proteínas de Ligação a DNA/genética , Masculino , Camundongos , Camundongos Knockout , Espermatogênese/genética , Ubiquitina-Proteína Ligases
8.
Fertil Steril ; 115(4): 811-812, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33832740

RESUMO

This introduction tees off an outstanding collection of Views and Reviews articles on the effects of the SARS-CoV-2 and COVID-19 on human reproductive health. These articles written by the experts in the field review the current literature on COVID-19 and male reproductive health, female reproductive health, and the assisted reproductive technology laboratory. Despite the prolonged nature of the pandemic and the number of people infected worldwide, there still are limited data on the effects of the virus and infection on human reproductive health and human fertility. The investigators distill a vast and often conflicting series of reports into a digestible summary to guide patient counseling and institute the safest practices into the assisted reproductive technology laboratory.


Assuntos
COVID-19 , Pandemias , Biópsia , Feminino , Humanos , Masculino , Saúde Reprodutiva , SARS-CoV-2 , Espermatogênese , Testículo
9.
Chin Med J (Engl) ; 134(10): 1152-1159, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33813517

RESUMO

BACKGROUND: Compared to adult studies, studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism (CHH) are limited and no universal treatment regimen is available. The aim of this study was to evaluate the feasibility of human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) therapy for treating male adolescents with CHH. METHODS: Male adolescent CHH patients were treated with hCG/hMG (n = 20) or a gonadotropin-releasing hormone (GnRH) pump (n = 21). The treatment was divided into a study phase (0-3 months) and a follow-up phase (3-12 months). The testicular volume (TV), penile length (PL), penis diameter (PD), and sex hormone levels were compared between the two groups. The TV and other indicators between the groups were analyzed using a t-test (equal variance) or a rank sum test (unequal variance). RESULTS: Before treatment, there was no statistical difference between the two groups in terms of the biochemistry, hormones, and other demographic indicators. After 3 months of treatment, the TV of the hCG/hMG and GnRH groups increased to 5.1 ±â€Š2.3 mL and 4.1 ±â€Š1.8 mL, respectively; however, the difference was not statistically significant (P > 0.05, t = 1.394). The PL reached 6.9 ±â€Š1.8 cm and 5.1 ±â€Š1.6 cm (P < 0.05, t = 3.083), the PD reached 2.4 ±â€Š0.5 cm and 2.0 ±â€Š0.6 cm (P < 0.05, t = 2.224), respectively, in the two groups. At the end of 6 months of treatment, biomarkers were in normal range in the two groups. Compared with the GnRH group, the testosterone (T) level and growth of PL and PD were significantly greater in the hCG/hMG group (all P < 0.05). While the TV of both groups increased, the difference was not statistically significant (P > 0.05, t = 0.314). After 9 to 12 months of treatment, the T level was higher in the hCG/hMG group. Other parameters did not exhibit a statistical difference. CONCLUSIONS: The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH. The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy. Furthermore, results from the extended time-period showed positive outcomes at the 1-year mark; however, the long-term effectiveness, strengths, and weaknesses of the hCG/hMG regimen require further research. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02880280; https://clinicaltrials.gov/ct2/show/NCT02880280.


Assuntos
Hipogonadismo , Menotropinas , Adolescente , Adulto , Criança , Gonadotropina Coriônica/uso terapêutico , Hormônio Liberador de Gonadotropina , Humanos , Hipogonadismo/tratamento farmacológico , Masculino , Menotropinas/uso terapêutico , Espermatogênese , Testosterona
10.
Int J Mol Sci ; 22(6)2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33805594

RESUMO

MicroRNAs applications were vastly studied throughout the years, spanning from potential cancer biomarkers to targeted therapies for various diseases. Out of these utilizations, this paper focuses on their role in male infertility. Approximately 10-15% of worldwide couples are affected by infertility. Out of these, 50% are due to male determinants. The majority of cases still have an undetermined cause. Previous studies have found that the aberrant expression of microRNAs could be linked to certain reproductive dysfunctions in males. Further on, this study looked into the most recent literature published on this subject in order to assess the connection between the up-/down-regulation of various microRNAs and the roles they play in male infertility. MicroRNAs were found to be abundant and stable in the seminal liquid, which led to a facile identification using regular RNA detection methods. It was observed that the concentration of microRNAs in semen was modified in the case of patients suffering from asthenozoospermia and azoospermia. Moreover, idiopathic male infertility was associated with a single nucleotide polymorphism of the microRNA binding site. Future studies should focus their attention on discovering future treatments against male infertility targeting specific microRNAs and also on developing new and improved contraceptive methods.


Assuntos
Proteínas Argonauta/genética , Astenozoospermia/genética , Azoospermia/genética , Infertilidade Masculina/genética , MicroRNAs/genética , Complexo de Inativação Induzido por RNA/genética , Adulto , Proteínas Argonauta/metabolismo , Astenozoospermia/metabolismo , Astenozoospermia/patologia , Azoospermia/metabolismo , Azoospermia/patologia , Sítios de Ligação , Regulação da Expressão Gênica , Humanos , Infertilidade Masculina/metabolismo , Infertilidade Masculina/patologia , Masculino , MicroRNAs/metabolismo , Polimorfismo de Nucleotídeo Único , Complexo de Inativação Induzido por RNA/metabolismo , Sêmen/citologia , Sêmen/metabolismo , Espermatogênese/genética
11.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33806855

RESUMO

Azoospermia affects 1% of men, and it can be due to: (i) hypothalamic-pituitary dysfunction, (ii) primary quantitative spermatogenic disturbances, (iii) urogenital duct obstruction. Known genetic factors contribute to all these categories, and genetic testing is part of the routine diagnostic workup of azoospermic men. The diagnostic yield of genetic tests in azoospermia is different in the different etiological categories, with the highest in Congenital Bilateral Absence of Vas Deferens (90%) and the lowest in Non-Obstructive Azoospermia (NOA) due to primary testicular failure (~30%). Whole-Exome Sequencing allowed the discovery of an increasing number of monogenic defects of NOA with a current list of 38 candidate genes. These genes are of potential clinical relevance for future gene panel-based screening. We classified these genes according to the associated-testicular histology underlying the NOA phenotype. The validation and the discovery of novel NOA genes will radically improve patient management. Interestingly, approximately 37% of candidate genes are shared in human male and female gonadal failure, implying that genetic counselling should be extended also to female family members of NOA patients.


Assuntos
Azoospermia/diagnóstico , Azoospermia/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Alelos , Animais , Biomarcadores , Deleção Cromossômica , Cromossomos Humanos Y , Feminino , Testes Genéticos , Humanos , Masculino , Fenótipo , Espermatogênese/genética , Sequenciamento Completo do Exoma
12.
Int J Mol Sci ; 22(8)2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33921254

RESUMO

Over the past decade, telomeres have attracted increasing attention due to the role they play in human fertility. However, conflicting results have been reported on the possible association between sperm telomere length (STL) and leukocyte telomere length (LTL) and the quality of the sperm parameters. The aim of this study was to run a comprehensive study to investigate the role of STL and LTL in male spermatogenesis and infertility. Moreover, the association between the sperm parameters and 11 candidate single nucleotide polymorphisms (SNPs), identified in the literature for their association with telomere length (TL), was investigated. We observed no associations between sperm parameters and STL nor LTL. For the individual SNPs, we observed five statistically significant associations with sperm parameters: considering a p < 0.05. Namely, ACYP2-rs11125529 and decreased sperm motility (p = 0.03); PXK-rs6772228 with a lower sperm count (p = 0.02); NAF1-rs7675998 with increased probability of having abnormal acrosomes (p = 0.03) and abnormal flagellum (p = 0.04); ZNF208-rs8105767 and reduction of sperms with normal heads (p = 0.009). This study suggests a moderate involvement of telomere length in male fertility; however, in our analyses four SNPs were weakly associated with sperm variables, suggesting the SNPs to be pleiotropic and involved in other regulatory mechanisms independent of telomere homeostasis, but involved in the spermatogenic process.


Assuntos
Hidrolases Anidrido Ácido/genética , Infertilidade Masculina/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas do Tecido Nervoso/genética , Proteínas Serina-Treonina Quinases/genética , Ribonucleoproteínas/genética , Telômero/genética , Acrossomo/metabolismo , Acrossomo/patologia , Adulto , Feminino , Estudos de Associação Genética , Humanos , Infertilidade Masculina/patologia , Leucócitos/metabolismo , Leucócitos/patologia , Masculino , Polimorfismo de Nucleotídeo Único/genética , Espermatogênese/genética , Espermatozoides/metabolismo , Espermatozoides/patologia , Homeostase do Telômero/genética
13.
Life Sci ; 274: 119336, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33716061

RESUMO

AIMS: This study aimed to explore the therapeutic effects of amniotic fluid-derived extracellular vesicles including exosomes (AF-Exos) on the recovery of sperm production capacity in a rat model of azoospermia. MAIN METHODS: The non-obstructive azoospermia (NOA) was induced in rats using intratesticular administration of Busulfan. Azoospermia was confirmed by testis histology. AF-Exos samples containing 10 or 40 µg exosomal proteins were injected into testicular tissue of NOA rats. After two months, the recovery of spermatogenesis was monitored via histopathological staining, spermiogram, and hormonal analysis. Immunohistochemistry staining for OCT-3/4 was used to identify of spermatogonial progenitors. The expression of DAZL and VASA, was also measured. KEY FINDINGS: AF-Exos exhibited sphere-shaped morphology with the mean diameter and zeta potential of 50 ± 7.521 nm and -7.16 mV. Immunoblots revealed that isolated nanoparticles were CD63, CD9, and CD81 positive. Histopathological evaluation revealed that spermatogenesis was improved significantly in NOA rats after AF-Exos injection. Data showed that the sperm parameters and spermatogenesis index were significantly improved after AF-Exos injection compared to azoospermic groups. OCT-3/4+ cells were increased in NOA rats after AF-Exos injection, showing the restoration of spermatogenesis. In the present study, both doses of exosome (10 and 40 µg) restored the testicular function of NOA rats. DAZL and VASA were increased significantly in animals who received 40 µg exosomal protein compared to azoospermic rats. Except in a high dose of AF-Exos (40 µg) for Testosterone and FSH, no statistically significant differences were found regarding hormones post-exosome injection. SIGNIFICANCE: Our study demonstrated that AF-Exos regenerated spermatogenesis and improved sperm quality in NOA rats.


Assuntos
Líquido Amniótico/química , Azoospermia/terapia , Bussulfano/toxicidade , Exossomos/metabolismo , Espermatogênese , Alquilantes/toxicidade , Animais , Azoospermia/induzido quimicamente , Azoospermia/metabolismo , Azoospermia/patologia , Exossomos/química , Masculino , Ratos , Ratos Wistar
14.
Int J Mol Sci ; 22(4)2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33670439

RESUMO

The spermatogonial stem cell (SSC) is a unique adult stem cell that requires tight physiological regulation during development and adulthood. As the foundation of spermatogenesis, SSCs are a potential tool for the treatment of infertility. Understanding the factors that are necessary for lifelong maintenance of a SSC pool in vivo is essential for successful in vitro expansion and safe downstream clinical usage. This review focused on the current knowledge of prepubertal testicular development and germ cell metabolism in different species, and implications for translational medicine. The significance of metabolism for cell biology, stem cell integrity, and fate decisions is discussed in general and in the context of SSC in vivo maintenance, differentiation, and in vitro expansion.


Assuntos
Células-Tronco Germinativas Adultas/fisiologia , Técnicas de Cultura de Células/métodos , Diferenciação Celular/fisiologia , Espermatogênese/fisiologia , Espermatogônias/fisiologia , Adulto , Células-Tronco Germinativas Adultas/citologia , Animais , Células Cultivadas , Humanos , Masculino , Espermatogônias/citologia
15.
Int J Mol Sci ; 22(4)2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33671837

RESUMO

Zinc (Zn), the second-most necessary trace element, is abundant in the human body. The human body lacks the capacity to store Zn; hence, the dietary intake of Zn is essential for various functions and metabolism. The uptake of Zn during its transport through the body is important for proper development of the three major accessory sex glands: the testis, epididymis, and prostate. It plays key roles in the initial stages of germ cell development and spermatogenesis, sperm cell development and maturation, ejaculation, liquefaction, the binding of spermatozoa and prostasomes, capacitation, and fertilization. The prostate releases more Zn into the seminal plasma during ejaculation, and it plays a significant role in sperm release and motility. During the maternal, labor, perinatal, and neonatal periods, the part of Zn is vital. The average dietary intake of Zn is in the range of 8-12 mg/day in developing countries during the maternal period. Globally, the dietary intake of Zn varies for pregnant and lactating mothers, but the average Zn intake is in the range of 9.6-11.2 mg/day. The absence of Zn and the consequences of this have been discussed using critical evidence. The events and functions of Zn related to successful fertilization have been summarized in detail. Briefly, our current review emphasizes the role of Zn at each stage of human reproduction, from the spermatogenesis process to childbirth. The role of Zn and its supplementation in in vitro fertilization (IVF) opens opportunities for future studies on reproductive biology.


Assuntos
Genitália Feminina/fisiologia , Espermatogênese/fisiologia , Zinco/fisiologia , Suplementos Nutricionais , Feminino , Humanos , Infertilidade/dietoterapia , Masculino , Gravidez , Espermatozoides/fisiologia , Testículo/fisiologia , Zinco/farmacologia
16.
Int J Mol Sci ; 22(4)2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33669425

RESUMO

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.


Assuntos
Acrossomo/patologia , Fertilização In Vitro/métodos , Deleção de Genes , Infertilidade Masculina/genética , Proteínas/genética , Acrossomo/metabolismo , Acrossomo/ultraestrutura , Animais , Sistemas CRISPR-Cas , Modelos Animais de Doenças , Feminino , Infertilidade Masculina/metabolismo , Gotículas Lipídicas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Gravidez , Proteínas/metabolismo , Motilidade Espermática/genética , Espermatogênese/genética , Testículo/metabolismo
17.
Artigo em Inglês | MEDLINE | ID: mdl-33670275

RESUMO

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.


Assuntos
Infertilidade Masculina , Nanopartículas , Humanos , Infertilidade Masculina/induzido quimicamente , Masculino , Nanopartículas/toxicidade , Estresse Oxidativo , Contagem de Espermatozoides , Motilidade Espermática , Espermatogênese , Espermatozoides/metabolismo , Testículo/metabolismo , Testosterona/metabolismo
18.
Arch Insect Biochem Physiol ; 106(4): e21779, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33660341

RESUMO

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.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Proteínas do Tecido Nervoso/metabolismo , Espermatogênese/fisiologia , Animais , Drosophila melanogaster/metabolismo , Drosophila melanogaster/fisiologia , Feminino , Masculino , Ovário/metabolismo , Testículo/metabolismo
19.
Syst Biol Reprod Med ; 67(1): 3-23, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33719829

RESUMO

The COVID-19 pandemic has led to a worldwide health emergency that has impacted 188 countries at last count. The rapid community transmission and relatively high mortality rates with COVID-19 in modern times are relatively unique features of this flu pandemic and have resulted in an unparalleled global health crisis. SARS-CoV-2, being a respiratory virus, mainly affects the lungs, but is capable of infecting other vital organs, such as brain, heart and kidney. Emerging evidence suggests that the virus also targets male and female reproductive organs that express its main receptor ACE2, although it is as yet unclear if this has any implications for human fertility. Furthermore, professional bodies have recommended discontinuing fertility services during the pandemic such that reproductive services have also been affected. Although increased safety measures have helped to mitigate the propagation of COVID-19 in a number of countries, it seems that there is no predictable timeline to containment of the virus, a goal likely to remain elusive until an effective vaccine becomes available  and widely distributed across the globe. In parallel, research on reproduction has been postponed for obvious reasons, while diagnostic tests that detect the virus or antibodies against it are of vital importance to support public health policies, such as social distancing and our obligation to wear masks in public spaces. This review aims to provide an overview of critical research and ethics issues that have been continuously emerging in the field of reproductive medicine as the COVID-19 pandemic tragically unfolds.Abbreviations: ACE2: angiotensin- converting enzyme 2; ART: Assisted reproductive technology; ASRM: American Society for Reproductive Medicine; CCR9: C-C Motif Chemokine Receptor 9; CDC: Centers for Disease Control and Prevention; COVID-19: Coronavirus disease 2019; Ct: Cycle threshold; CXCR6: C-X-C Motif Chemokine Receptor 6; ELISA: enzyme-linked immunosorbent assay; ESHRE: European Society of Human Reproduction and Embryology; ET: Embryo transfer; FSH: Follicle Stimulating Hormone; FFPE: formalin fixed paraffin embedded; FYCO1: FYVE And Coiled-Coil Domain Autophagy Adaptor 1; IFFS: International Federation of Fertility Societies; IUI: Intrauterine insemination; IVF: In vitro fertilization; LH: Luteinizing Hormone; LZTFL1: Leucine Zipper Transcription Factor Like 1; MAR: medically assisted reproduction services; MERS: Middle East Respiratory syndrome; NGS: Next Generation Sequencing; ORF: Open Reading Frame; PPE: personal protective equipment; RE: RNA Element; REDa: RNA Element Discovery algorithm; RT-PCR: Reverse=trascriptase transcriptase-polymerase chain reaction; SARS: Severe acute respiratory syndrome; SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2; SLC6A20: Solute Carrier Family 6 Member 20; SMS: Single Molecule Sequencing; T: Testosterone; TMPRSS2: transmembrane serine protease 2; WHO: World Health Organization; XCR1: X-C Motif Chemokine Receptor.


Assuntos
COVID-19 , Fertilidade , Interações Hospedeiro-Patógeno , Reprodução , SARS-CoV-2/fisiologia , Animais , Pesquisa Biomédica , Teste para COVID-19 , Genitália/virologia , Humanos , Medicina Reprodutiva/ética , Técnicas de Reprodução Assistida , Espermatogênese
20.
Int J Mol Sci ; 22(5)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652607

RESUMO

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.


Assuntos
Fator Estimulador de Colônias de Macrófagos/metabolismo , Espermatogênese , Testículo/metabolismo , Animais , Humanos , Masculino , Camundongos , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/metabolismo , Testículo/citologia
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