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1.
J Exp Zool A Ecol Integr Physiol ; 341(2): 138-150, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38047873

RESUMO

Although the usage of nanoparticles has expanded substantially in recent years, and it causes the detrimental effect on the various organs. CuNPs are widely used in commercial applications. There has been minimal investigation into the possibly harmful effects of CuNPs on the accessory reproductive organs. Thus, the present study aimed to investigate the effect of CuNPs on the male reproductive organs like epididymis, vas deferens, seminal vesicle and prostate of mice. The mice were exposed orally to CuNPs at three doses 10, 100, and 200 mg/kg for 70 days. Our results showed that the organs index of only vas deferens and prostate reduced at 200 mg/kg group compared to the control. However, the histological study showed degenerative changes in the epididymis at higher doses like distortion in the tubules. The sperm parameters were also decreased in the 200 mg/kg CuNPs group. The vas deferens in 100 and 200 mg/kg treatment groups exhibited detachment of luminal epithelium and with a few or no spermatozoa in the higher dose group. The seminal vesicle and prostate also showed degenerative changes like atrophy, hyperplasia, and scant secretary materials. Furthermore, CuNPs also increased the oxidative stress and decreased antioxidant enzymes in vas deferens and seminal vesicles at higher dose. Caput epididymis showed decreased GPx enzymes in all the groups. However, MDA and GPx in corpus, cauda, and prostate did not show any significant variations among all the groups. In conclusion, our results suggest that CuNPs can manifest the detrimental effect of the male accessory organs and epididymis in a dose and tissue dependent manner. Since, detrimental effects were observed only at higher dose, thus, uses of CuNPs would be safe for reproductive organs at lower dose, even for the prolonged duration.


Assuntos
Cobre , Epididimo , Masculino , Camundongos , Animais , Epididimo/patologia , Cobre/farmacologia , Sêmen , Ducto Deferente/patologia , Próstata/patologia
2.
Ther Adv Respir Dis ; 17: 17534666231216566, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38084849

RESUMO

BACKGROUND: Lung cancer is the most common cause of malignant pleural effusion (MPE). Serum human epididymis secretory protein 4 (HE4) is a useful diagnostic marker for lung cancer. OBJECTIVE: This study aimed to evaluate the diagnostic accuracy of pleural fluid HE4 for MPE. DESIGN: A prospective, double-blind diagnostic test accuracy study. METHODS: Patients with undiagnosed pleural effusion were enrolled in two cohorts (Hohhot and Changshu). Electrochemiluminescence immunoassay was used to detect pleural fluid HE4. The diagnostic accuracy of HE4 was evaluated by a receiver operating characteristic (ROC) curve, and the net benefit of HE4 was assessed by a decision curve analysis (DCA). RESULTS: A total of 66 MPEs and 86 benign pleural effusions (BPEs) were enrolled in the Hohhot cohort. In the Changshu cohort, 26 MPEs and 32 BPEs were enrolled. In both cohorts, MPEs had significantly higher pleural fluid HE4 than BPEs. The area under the ROC curve (AUC) of HE4 was 0.73 (95% CI: 0.64-0.81) in the Hohhot cohort and 0.79 (95% CI: 0.67-0.91) in the Changshu cohort. At a threshold of 1300 pmol/L, HE4 had sensitivities of 0.44 (95% CI: 0.33-0.56) in the Hohhot cohort and 0.54 (95% CI: 0.35-0.73) in the Changshu cohort. The corresponding specificities were 0.90 (95% CI: 0.83-0.95) in the Hohhot cohort and 0.94 (95% CI: 0.84-1.00) in the Changshu cohort. In subgroup analyses, HE4 had an AUC (95% CI) of 0.78 (0.71-0.85) in exudates and an AUC of 0.69 (0.57-0.81) in patients with negative effusion cytology. The DCA revealed that HE4 determination had a net benefit in both cohorts. CONCLUSION: Pleural fluid HE4 has moderate diagnostic accuracy for MPE and has net benefit in pleural effusion patients with unknown etiology.


Assuntos
Neoplasias Pulmonares , Derrame Pleural Maligno , Derrame Pleural , Humanos , Masculino , Biomarcadores Tumorais/metabolismo , Epididimo/metabolismo , Epididimo/patologia , Exsudatos e Transudatos/metabolismo , Neoplasias Pulmonares/patologia , Derrame Pleural/diagnóstico , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/patologia , Estudos Prospectivos , Método Duplo-Cego
3.
J Vet Diagn Invest ; 35(5): 568-572, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37395186

RESUMO

A 12-y-old, male Dachshund was presented for elective orchiectomy. The testes were of normal size. The left testis had numerous dark-red, blood clot-like foci within the vaginal tunic over the pampiniform plexus, epididymis, and testis. Histologically, the red foci were limited to the vaginal tunic and consisted of disorderly growing, variably sized, thin-walled blood vessels lined by a single layer of endothelial cells without mitoses and supported by a thin layer of pericytes. The blood vessels were distended by erythrocytes without thrombus formation. Endothelial cells had cytoplasmic immunolabeling for CD31; pericytes had strong cytoplasmic immunolabeling for α-smooth muscle actin. Our case of subclinical unilateral vascular hamartomas of the vaginal tunic in a dog has not been reported previously in domestic animals or humans, to our knowledge.


Assuntos
Doenças do Cão , Hamartoma , Trombose , Humanos , Feminino , Animais , Masculino , Cães , Células Endoteliais/patologia , Testículo/patologia , Epididimo/patologia , Trombose/veterinária , Hamartoma/diagnóstico , Hamartoma/veterinária , Hamartoma/patologia , Doenças do Cão/diagnóstico , Doenças do Cão/cirurgia , Doenças do Cão/patologia
4.
Medicina (Kaunas) ; 59(7)2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37512071

RESUMO

Background: Paratesticular tumors (PTs) are very uncommon, accounting for almost 5% of intrascrotal tumors. Of these, adenomatoid tumors (ATs) represent about 30% and most frequently arise in the tail of the epididymis. Ultrasound (US) examination is the first-choice imaging method employed for the evaluation of the scrotum. Unfortunately, there are no specific US-imaging features useful for distinguishing an AT from a malignant lesion. To increase diagnostic accuracy and confidence, new sonographic techniques have incorporated real-time tissue elastography (RTE) under the assumption that malignant lesions are "harder" than benign lesions. Case report: In our paper, we describe a very rare case of a 60-year-old patient with a giant paratesticular mass mimicking malignancy when examined using RTE, i.e., it was stiffer than the surrounding tissue (a hard pattern), which, upon histologic examination, was identified as an AT. Discussion: Our case underscores that there is also a significant overlap between different types of scrotal lesions when RTE is used for examination. Thus, if a PT is found, the imaging approach should always be supplemented with more definitive diagnostic methods, such as FNAC or FNAB, which are the only diagnostic methods capable of leading to a certain diagnosis. Conclusions: Alongside underlining the importance of pre-operative imaging for making correct diagnoses and selecting the correct therapy, we wish to draw our readers' attention to this report in order to demonstrate the clinical implications of a giant AT presenting as stiff lesions when examined using SE.


Assuntos
Tumor Adenomatoide , Técnicas de Imagem por Elasticidade , Neoplasias dos Genitais Masculinos , Masculino , Humanos , Pessoa de Meia-Idade , Tumor Adenomatoide/diagnóstico por imagem , Tumor Adenomatoide/patologia , Escroto/diagnóstico por imagem , Escroto/patologia , Neoplasias dos Genitais Masculinos/diagnóstico por imagem , Neoplasias dos Genitais Masculinos/patologia , Epididimo/patologia
5.
Vet Immunol Immunopathol ; 261: 110621, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37348444

RESUMO

Ovine brucellosis is an infectious disease that causes alterations in the reproductive tract in ram and abortion in ewes. Their negative economic impact in ovine production warrants a thorough understanding the interactions between B. ovis and the host. Here, epididymis lesions of rams infected by B. ovis were histopathologically staged into early and advanced. Expression by immunohistochemistry of Brucella antigens, inflammatory cell markers (CD3, CD79αcy) and cytokines (IFN-γ, TNF-α, TGF-ß1) was assessed in both stages. Early lesions were characterized by epithelial changes, interstitial inflammation, and mild fibrosis; whereas advanced lesions displayed caseous granulomas containing numerous macrophages, multinucleated giant cells, lymphocytes, and plasma cells. Expression of Brucella antigens were observed in both stages. The cellular response in B. ovis lesions were predominantly of T-cells (CD3+) whereas low numbers of B-cells and plasma cells (CD79αcy+) were present in both early and advanced lesions. IFN-γ was expressed by lymphocytes in early lesions suggesting that the adaptive immune response against B. ovis is initiated by Th1 cells, this response was also preserved in advanced stages. Expression of TNF-α was observed in neutrophils of epithelial microabscesses and intraepithelial T-cells of early lesions suggesting a promotion of neutrophil phagocytosis triggered by TNF-α. On the other hand, advanced lesions showed a reduction of TNF-α expression which may permit B. ovis persistence in granulomas. Lastly, TGF-ß1 expression (fibroblast, macrophages and less in lymphocytes) were increased with time, suggesting that B. ovis promotes TGF-ß1 secretion promoting chronicity of the lesions.


Assuntos
Brucella ovis , Brucelose , Doenças dos Ovinos , Ovinos , Animais , Masculino , Feminino , Epididimo/patologia , Fator de Crescimento Transformador beta1 , Fator de Necrose Tumoral alfa , Brucelose/veterinária , Carneiro Doméstico
6.
Hinyokika Kiyo ; 69(4): 113-116, 2023 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-37183042

RESUMO

A 63-year-old man presented with right scrotal swelling. A physical examination revealed a painless, palpable mass in the right scrotum. The mass was well defined and lobulated. Subsequently, a diagnosis of right epididymal tumor was made, and right high orchiectomy was performed. Hematoxylin-eosin and immunostaining revealed leiomyosarcoma of the epididymis. When a diagnosis of epididymal malignant tumor is made, the standard treatment is radical orchiectomy.


Assuntos
Neoplasias dos Genitais Masculinos , Leiomiossarcoma , Masculino , Humanos , Pessoa de Meia-Idade , Epididimo/diagnóstico por imagem , Epididimo/cirurgia , Epididimo/patologia , Leiomiossarcoma/diagnóstico por imagem , Leiomiossarcoma/cirurgia , Neoplasias dos Genitais Masculinos/diagnóstico por imagem , Neoplasias dos Genitais Masculinos/cirurgia , Orquiectomia , Pelve
7.
BJOG ; 130(8): 941-948, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36715558

RESUMO

OBJECTIVE: To investigate serum human epididymis-4 (HE4) as a predictive biomarker of intrauterine progestin response in endometrial cancer and atypical endometrial hyperplasia (AEH). DESIGN: Prospective prognostic factor study. SETTING: Consecutive sample of women attending a tertiary gynaecological oncology centre in northwest England. POPULATION: Women with AEH or early-stage, low-grade endometrial cancer who were unfit for or declined primary surgical management. METHODS: A total of 76 women, 32 with AEH and 44 with endometrial cancer, were treated with a levonorgestrel intrauterine system (LNG-IUS) for 12 months. Endometrial biopsies and imaging were performed to assess treatment response. Pretreatment serum HE4 was analysed by chemiluminescence immunoassay and diagnostic accuracy and logistic regression analyses were performed. MAIN OUTCOME MEASURES: Progestin response at 12 months defined by histology and imaging. RESULTS: The median age and body mass index (BMI) of the final cohort were 52 years (interquartile range [IQR] 33-62 years) and 46 kg/m2 (IQR 38-54 kg/m2 ), respectively. Baseline serum HE4 was significantly higher in non-responders than responders (119.2 pmol/L, IQR 94.0-208.4 pmol/L versus 71.8 pmol/L, IQR 56.1-84.2 pmol/L, p < 0.001). Older age (odds ratio [OR] 0.96, 95% CI 0.93-0.99, p = 0.02), baseline serum HE4 (OR 0.97, 95% CI 0.96-0.99, p = 0.001) and endometrial cancer histology (OR 0.22, 95% CI 0.72-0.68, p = 0.009) were associated with a lower likelihood of progestin treatment response. Serum HE4 remained independently associated with progestin treatment failure when adjusted for age and histology (adjusted hazard ratio 0.97, 95% CI 0.96-0.99, p = 0.008). CONCLUSION: Serum HE4 shows promise as a predictive biomarker of progestin treatment response in endometrial cancer and AEH.


Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Dispositivos Intrauterinos Medicados , Lesões Pré-Cancerosas , Feminino , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Progestinas/uso terapêutico , Prognóstico , Hiperplasia/patologia , Estudos Prospectivos , Epididimo/patologia , Levanogestrel/uso terapêutico , Neoplasias do Endométrio/patologia , Hiperplasia Endometrial/patologia , Lesões Pré-Cancerosas/patologia , Biomarcadores
8.
Int J Surg Pathol ; 31(5): 866-871, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36474354

RESUMO

Leiomyoadenomatoid tumors of the epididymis are exceedingly rare biphasic tumors composed of an adenomatoid component in the form of gland-like structures lined by single flat or cuboidal cells admixed with smooth muscle. Radiological and gross findings cannot distinguish leiomyoadenomatoid tumors from the more common classic adenomatoid tumors or leiomyomas, and careful microscopic examination is critical in the identification of this esoteric variant. The histogenesis of this entity remains ambiguous. Common hypotheses include a collision tumor, a variant of an adenomatoid tumor with a smooth muscle component, or an adenomatoid tumor arising in the background of reactive smooth muscle hyperplasia. We present 2 cases of leiomyoadenomatoid tumors with diffuse nuclear WT1 positivity in both the adenomatoid and smooth muscle components, supporting the mesothelial origin of these tumors.


Assuntos
Adenoma , Tumor Adenomatoide , Leiomioma , Masculino , Humanos , Tumor Adenomatoide/patologia , Leiomioma/diagnóstico , Epididimo/patologia , Músculo Liso/patologia , Proteínas WT1
9.
Arch Razi Inst ; 78(4): 1239-1246, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-38226379

RESUMO

Tribulus Terrestris (TT) is a common herbal plant with different categories that grows in many countries of the world. Traditional Chinese and Indian therapies have used TT for infertility treatment and also as a powerful antioxidant agent. Therefore, this study aimed to use this plant supplemented with vitamin E to study their combined effects on the histological condition of the testicle and epididymis of rabbits. This study was performed on 28 healthy male rabbits (445-950 g, 2.0-3.0 months old) that were randomly divided into four groups (n=7). All animals were subjected to clinical examination to ensure that they were free of external and internal parasites with the use of some preventive treatments. The animals were housed individually (cage size: 50 cm×50 cm×40 cm) over the 60-day study period starting from January 2022, with an adaptation period of two weeks. Tribulus Terrestris and vitamin E treatments were as follows: the first group (G1) was daily fed on a standard diet and kept as the control group, the second group (G2) was daily fed on the same ration plus 1 g of TT (animal/daily), the third group (G3) was daily fed on the same ration plus 1 g of TT supplemented with 60 mg of vitamin E (orally) (animal /daily), and the fourth group (G4) was daily fed on the same ration, with the addition of 60 mg vitamin E per animal (orally). The morphometric investigation, macroscopic variables (including body weight, testicular weight, and volume), and the microscopic parameters of the testicular seminal tubule were measured. The histological section showed the absence of negative effects after the oral administration of TT at a dose of 1 g per day and 60 IU vitamin E for each animal. However, there was a positive effect on spermatogonia and spermatocytes in all animals, while the spermatogonia in the experimental groups were more dense, especially in the second and third groups, compared to the control group. The seminiferous tubules were significantly lined with spermatogonia, spermatocytes, and round spermatids (P<0.5) in the experimental groups, compared to the control group. Nevertheless, the epididymis tissue did not show traces of histological changes, such as epididymal hyperplasia. Sperms were more frequent in the lumens of the epididymis as well as the lumens larger than those of the control. Based on the results of this study, it can be concluded that the pole plant and vitamin E have a positive effect on the epithelial lining of the seminiferous tubules and the epididymis with an increase in sperm formation and differentiation towards maturity.


Assuntos
Testículo , Tribulus , Coelhos , Masculino , Animais , Testículo/patologia , Epididimo/patologia , Vitamina E/farmacologia , Espermatogênese , Sementes
10.
J Vet Diagn Invest ; 34(6): 1020-1022, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36184931

RESUMO

A 9-mo-old, male domestic shorthair cat was presented for castration because of mounting behavior observed by the owner. On physical examination, the cat was bilaterally cryptorchid, but had penile spines. Abdominal exploration through a midline laparotomy revealed 2 pairs of masses. All 4 masses had gross features of testes, and ranged from 7 × 5 × 5 mm to 12 × 6 × 7 mm, with associated epididymal tissue. Histologically, each mass contained seminiferous tubules consistent with testicular tissue, and epididymal tubules, confirming a diagnosis of polyorchidism; deferent ducts were not found. There was no evidence of neoplastic, infectious, or inflammatory disease. Mounting behavior ceased 4 wk post-surgery. Histologic confirmation of more than 2 testes is needed to establish a diagnosis of polyorchidism, a rare congenital anomaly that has been reported infrequently in the veterinary literature; reports have been of animals with triorchidism, with the exception of 1 cat with 4 intraabdominal testes. Our report emphasizes that, although rare, polyorchidism should be considered in cryptorchid cats, or whenever penile spines are present in a previously castrated cat. Our case also highlights the value of checking for penile spines in a bilaterally cryptorchid cat if abdominal ultrasound is not an option to aid in surgical planning.


Assuntos
Doenças do Gato , Criptorquidismo , Gatos , Masculino , Animais , Criptorquidismo/diagnóstico , Criptorquidismo/cirurgia , Criptorquidismo/veterinária , Testículo/diagnóstico por imagem , Testículo/cirurgia , Orquiectomia/veterinária , Ultrassonografia/veterinária , Epididimo/patologia , Doenças do Gato/diagnóstico por imagem , Doenças do Gato/cirurgia
11.
Andrology ; 10(8): 1660-1672, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36082398

RESUMO

BACKGROUND: The unique anatomy of the male reproductive organ reflects its complex function from sperm maturation to their storage for months until emission. Since light microscopy in two dimensions (2d) cannot sufficiently demonstrate its complex morphology, a comprehensive visualization is required to identify pathologic alterations in its entire anatomical context. OBJECTIVES: Aim of this study was to use three-dimensional (3d) light sheet fluorescence microscopy (LSFM) to visualize entire murine testes in 3d, label-free and at subcellular resolution, and to assign local autofluorescence to testicular and deferent structures. MATERIALS AND METHODS: Murine testes were fixed with four different fixatives and subsequently cleared with benzoic acid/benzyl benzoate. Hereafter, complete murine testes were scanned with LSFM with different fluorescence filter sets and subsequently embedded in paraffin for further conventional planar histology. RESULTS: Autofluorescence signals of the murine reproductive organ allowed the unambiguous identification of the testicular anatomy from the seminiferous tubules to the vas deferens with their specific stratification independent of the used fixative. Blood vessels were visualized from the pampiniform plexus to the small capillaries of single tubules. Moreover, due to the specific intrinsic fluorescence properties of the efferent ducts and the epididymis, luminal caliber, the epithelial stratification and retronuclear cytoplasmic inclusions gave a unique insight into the interface of both morphological structures. Subsequent 2d histology confirmed the identified morphological structures. DISCUSSION: LSFM analysis of the murine reproductive organ allows due to its intrinsic fluorescence a simple, label-free 3d assessment of its entire duct morphology, the epithelial composition, and the associated blood supply in its anatomical relation. CONCLUSION: LSFM provides the technical basis for comprehensive analyses of pathologically altered murine testes in its entirety by depicting specific autofluorescence. Thereby it facilitates mouse studies of testicular disease or their drug-related alterations in more detail potentially for clinical translation assessing human testicular biopsies.


Assuntos
Parafina , Sêmen , Animais , Ácido Benzoico , Epididimo/patologia , Fixadores , Humanos , Masculino , Camundongos , Microscopia de Fluorescência/métodos , Testículo
12.
Khirurgiia (Mosk) ; (9): 74-76, 2022.
Artigo em Inglês, Russo | MEDLINE | ID: mdl-36073586

RESUMO

Authors have developed technique of endoscopic inspection of scrotal organs allowing to visualize sufficiently well the poles of testis with head and tail of epididymis, posterior-lateral space behind the epididymis and to perform targeted biopsy of ovarian tissue thus decreasing traumatic effects of the operation. Endoscopy of scrotal organs has been performed in 11 patients with azoospermia of different origin. 18 endoscopic videosurgical examinations have been performed before carrying out Micro-TESE and 10 biopsies of ovarian tissue have been made under visual control with the same patients. Resection of hydatid with its torsion under the condition of artificial hydrocele has been performed in 1 patient with good results.


Assuntos
Azoospermia , Escroto , Epididimo/patologia , Humanos , Masculino , Pelve , Escroto/cirurgia , Testículo/patologia
13.
J Ultrasound ; 25(3): 675-685, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35038143

RESUMO

PURPOSE: To assess the utility of comprehensive sonographic examination including scrotal sonography, Testicular Doppler and Transrectal Ultrasound (TRUS) to evaluate the male reproductive system and differentiate between obstructive (OG) and non-obstructive (NOG) causes of azoospermia. METHODS: 30 infertile men with azoospermia and 30 control subjects with normospermia underwent sonographic evaluation. FNAC/biopsy findings were used for assigning a final diagnosis of obstructive or non-obstructive azoospermia. Qualitative and quantitative imaging parameters were retrospectively compared between the groups using Chi-square/Fisher's exact test and unpaired t-test, respectively. P < 0.05 was considered significant. RESULTS: Ectasia of rete testis/epididymal tubules, altered epididymal echogenicity, dilated terminal vas deferens were significantly more common in OG while inhomogeneous testicular echo-texture and reduced testicular vascularity were more common in NOG (P < 0.05). Testicular volume and epididymal head size were significantly higher in OG than in NOG and controls (18.2 ml/10 mm Vs 8.2 ml/7.2 mm and 13.4 ml/8.8 mm respectively; P < 0.05); while Resistive Index (RI) of intra-testicular vessels was higher in NOG as compared to OG and controls (0.65 vs 0.54 and 0.52 respectively; P < 0.05). On ROC curve analysis, cut-off values of testicular volume (AUC: 0.939; P < 0.001), epididymal head size (AUC: 0.772; P = 0.001) and testicular RI (AUC: 0.761; P = 0.001) to differentiate between the groups were 12.1 ml (sensitivity-94.4%; specificity-83.3%), 9 mm (sensitivity-66.7%; specificity-71%) and 0.62 (sensitivity-62%; specificity-100%) respectively. CONCLUSION: Comprehensive sonographic evaluation can be used to differentiate obstructive from non-obstructive infertility and should be routinely incorporated in the diagnostic workup of infertile men with azoospermia.


Assuntos
Azoospermia , Infertilidade Masculina , Azoospermia/diagnóstico por imagem , Azoospermia/patologia , Epididimo/diagnóstico por imagem , Epididimo/patologia , Humanos , Infertilidade Masculina/diagnóstico por imagem , Infertilidade Masculina/patologia , Masculino , Estudos Retrospectivos , Testículo/diagnóstico por imagem , Testículo/patologia , Ultrassonografia
14.
G3 (Bethesda) ; 12(2)2022 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-34878116

RESUMO

The high mobility group AT-hook 2 (HMGA2) protein works as an architectural regulator by binding AT-rich DNA sequences to induce conformational changes affecting transcription. Genomic deletions disrupting HMGA2 coding sequences and flanking noncoding sequences cause dwarfism in mice and rabbits. Here, CRISPR/Cas9 was used in mice to generate an Hmga2 null allele that specifically disrupts only the coding sequence. The loss of one or both alleles of Hmga2 resulted in reduced body size of 20% and 60%, respectively, compared to wild-type littermates as well as an allometric reduction in skull length in Hmga2-/- mice. Both male and female Hmga2-/- mice are infertile, whereas Hmga2+/- mice are fertile. Examination of reproductive tissues of Hmga2-/- males revealed a significantly reduced size of testis, epididymis, and seminal vesicle compared to controls, and 70% of knock-out males showed externalized penis, but no cryptorchidism was observed. Sperm analyses revealed severe oligospermia in mutant males and slightly decreased sperm viability, increased DNA damage but normal sperm chromatin compaction. Testis histology surprisingly revealed a normal seminiferous epithelium, despite the significant reduction in testis size. In addition, Hmga2-/- mice showed a significantly reduced exploratory behavior. In summary, the phenotypic effects in mouse using targeted mutagenesis confirmed that Hmga2 is affecting prenatal and postnatal growth regulation, male reproductive tissue development, and presents the first indication that Hmga2 function is required for normal mouse behavior. No specific effect, despite an allometric reduction, on craniofacial development was noted in contrast to previous reports of an altered craniofacial development in mice and rabbits carrying deletions of both coding and noncoding sequences at the 5' part of Hmga2.


Assuntos
Epididimo , Proteína HMGA2/metabolismo , Infertilidade , Animais , Epididimo/metabolismo , Epididimo/patologia , Feminino , Transtornos do Crescimento/metabolismo , Transtornos do Crescimento/patologia , Proteína HMGA2/genética , Infertilidade/metabolismo , Infertilidade/patologia , Masculino , Camundongos , Gravidez , Coelhos , Reprodução/genética , Testículo/metabolismo
15.
Am J Pathol ; 192(1): 121-129, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34626576

RESUMO

The pathogenesis of Ebola virus disease (EVD) is still incomplete, in spite of the availability of a nonhuman primate modelfor more than 4 decades. To further investigate EVD pathogenesis, a natural history study was conducted using 27 Chinese-origin rhesus macaques. Of these, 24 macaques were exposed intramuscularly to Kikwit Ebola virus and euthanized at predetermined time points or when end-stage clinical disease criteria were met, and 3 sham-exposed macaques were euthanized on study day 0. This study showed for the first time that Ebola virus causes uterine cervicitis, vaginitis, posthitis, and medullary adrenalitis. Not only was Ebola virus detected in the interstitial stromal cells of the genital tract, but it was also present in the epididymal and seminal vesicular tubular epithelial cells, ectocervical and vaginal squamous epithelial cells, and seminal fluid. Furthermore, as early as day 3 after exposure, Ebola virus replicative intermediate RNA was detected in Kupffer cells and hepatocytes. These findings in the nonhuman model provide additional insight into potential sexual transmission, possible disruption of sympathetic hormone production, and early virus replication sites in human EVD patients.


Assuntos
Ebolavirus/fisiologia , Hormônios/metabolismo , Fígado/virologia , Tropismo/fisiologia , Replicação Viral/fisiologia , Animais , Células Cromafins/patologia , Células Cromafins/virologia , Modelos Animais de Doenças , Epididimo/patologia , Epididimo/virologia , Células Epiteliais/patologia , Células Epiteliais/virologia , Feminino , Hepatócitos/patologia , Hepatócitos/virologia , Células de Kupffer/patologia , Células de Kupffer/virologia , Macaca mulatta , Masculino , Cervicite Uterina/patologia , Cervicite Uterina/virologia , Vaginite/patologia , Vaginite/virologia
16.
J Dev Orig Health Dis ; 13(1): 20-27, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33441200

RESUMO

The consumption of fructose has increased in children and adolescents and is partially responsible for the high incidence of metabolic diseases. The lifestyle during postnatal development can result in altered metabolic programming, thereby impairing the reproductive system and fertility during adulthood. Therefore, the aim of this study was to evaluate the effect of a high-fructose diet in the male reproductive system of pubertal and adult rats. Male Wistar rats (30 d old) were assigned to four different groups: Fr30, which received fructose (20%) in water for 30 d and were euthanized at postnatal day (PND) 60; Re-Fr30, which received fructose (20%) for 30 d and were euthanized at PND 120; and two control groups C30 and Re-C30, which received water ad libitum and were euthanized at PND 60 and 120, respectively. Fructose induced an increase in abnormal seminiferous tubules with epithelial vacuoles, degeneration, and immature cells in the lumen. Moreover, Fr30 rats showed altered spermatogenesis and daily sperm production (DSP), as well as increased serum testosterone concentrations. After discontinuing high-fructose consumption, DSP and sperm number decreased significantly. We observed tissue remodeling in the epididymis, with a reduction in stromal and epithelial compartments that might have influenced sperm motility. Therefore, we concluded that fructose intake in peripubertal rats led to changes in the reproductive system observed both during puberty and adulthood.


Assuntos
Epididimo/patologia , Qualidade dos Alimentos , Xarope de Milho Rico em Frutose/efeitos adversos , Testículo/patologia , Animais , Modelos Animais de Doenças , Epididimo/efeitos dos fármacos , Epididimo/fisiopatologia , Xarope de Milho Rico em Frutose/metabolismo , Masculino , Puberdade/sangue , Puberdade/metabolismo , Ratos Wistar/crescimento & desenvolvimento , Ratos Wistar/metabolismo , Contagem de Espermatozoides/métodos , Contagem de Espermatozoides/estatística & dados numéricos , Testículo/efeitos dos fármacos , Testículo/fisiopatologia , Testosterona/análise , Testosterona/sangue
18.
Toxicology ; 460: 152886, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34352348

RESUMO

Arsenic intoxication affects male reproductive parameters of prepubertal rats. Besides, morphological and functional alterations in their testis and epididymis may remain after withdrawal of arsenic insult, causing potential impairment in male fertility during adulthood. In this study, we aimed at analyzing the effect of prepubertal arsenic exposure on the fecundity of epididymal sperm from sexually mature Wistar rats, assessing fertility indexes, sperm parameters, and sperm phosphoproteins content. Male pups on postnatal day (PND) 21 received filtered water (controls, n = 10) and 10 mg L-1 arsenite (n = 10) daily for 30 days. From PND52 to PND81, rats from both groups received filtered water. During this period, the males mated with non-exposed females between PND72 and PND75. Our results showed that sexually mature rats presented low sperm production, epididymal sperm count, motility, and quality after prepubertal arsenic exposure. These findings possibly contributed to the low fertility potential and high preimplantation loss. Epididymal sperm proteome detected 268 proteins, which 170 were found in animals from both control and arsenic groups, 27 proteins were detected only in control animals and 71 proteins only in arsenic-exposed rats. In these animals, SPATA 18 and other five proteins were upregulated, whereas keratin type II cytoskeletal 1 was downregulated (q < 0.1). The results of KEGG pathway analysis demonstrated an enrichment of pathways related to dopaminergic response, adrenergic signaling, protein degradation, and oocyte meiosis in arsenic-exposed animals. Moreover, 26 proteins were identified by phosphoproteomic with different phosphorylation pattern in animals from both groups, but SPATA18 was phosphorylated only in arsenic-exposed animals. We concluded that prepubertal exposure to arsenic is deleterious to sperm quality and male fertility, altering the sperm phosphoproteins profile.


Assuntos
Arsênio/toxicidade , Epididimo/metabolismo , Fertilidade/fisiologia , Fosfoproteínas/metabolismo , Maturidade Sexual/fisiologia , Espermatozoides/metabolismo , Animais , Arsênio/administração & dosagem , Bovinos , Epididimo/efeitos dos fármacos , Epididimo/patologia , Fertilidade/efeitos dos fármacos , Humanos , Masculino , Camundongos , Ratos , Ratos Wistar , Reprodução/efeitos dos fármacos , Reprodução/fisiologia , Maturidade Sexual/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia
19.
Nutrients ; 13(6)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201185

RESUMO

High-protein diets (HPDs) are widely accepted as a way to stimulate muscle protein synthesis when combined with resistance training (RT). However, the effects of HPDs on adipose tissue plasticity and local inflammation are yet to be determined. This study investigated the impact of HPDs on glucose control, adipocyte size, and epididymal adipose inflammatory biomarkers in resistance-trained rats. Eighteen Wistar rats were randomly assigned to four groups: normal-protein (NPD; 17% protein total dietary intake) and HPD (26.1% protein) without RT and NPD and HPD with RT. Trained groups received RT for 12 weeks with weights secured to their tails. Glucose and insulin tolerance tests, adipocyte size, and an array of cytokines were determined. While HPD without RT induced glucose intolerance, enlarged adipocytes, and increased TNF-α, MCP-1, and IL1-ß levels in epididymal adipose tissue (p < 0.05), RT diminished these deleterious effects, with the HPD + RT group displaying improved blood glucose control without inflammatory cytokine increases in epididymal adipose tissue (p < 0.05). Furthermore, RT increased glutathione expression independent of diet (p < 0.05). RT may offer protection against adipocyte hypertrophy, pro-inflammatory states, and glucose intolerance during HPDs. The results highlight the potential protective effects of RT to mitigate the maladaptive effects of HPDs.


Assuntos
Glicemia/metabolismo , Dieta Rica em Proteínas , Inflamação/sangue , Gordura Intra-Abdominal/patologia , Treinamento de Força , Adipócitos/patologia , Animais , Tamanho Celular , Dieta , Epididimo/patologia , Glutationa/metabolismo , Resistência à Insulina , Masculino , Tamanho do Órgão , Ratos Wistar , Aumento de Peso
20.
Reproduction ; 162(2): 129-139, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34085951

RESUMO

Cilia are evolutionarily conserved microtubule-based structures that perform diverse biological functions. Cilia are assembled on basal bodies and anchored to the plasma membrane via distal appendages. In the male reproductive tract, multicilia in efferent ducts (EDs) move in a whip-like motion to prevent sperm agglutination. Previously, we demonstrated that the distal appendage protein CEP164 recruits Chibby1 (Cby1) to basal bodies to facilitate basal body docking and ciliogenesis. Mice lacking CEP164 in multiciliated cells (MCCs) (FoxJ1-Cre;CEP164fl/fl) show a significant loss of multicilia in the trachea, oviduct, and ependyma. In addition, we observed male sterility; however, the precise role of CEP164 in male fertility remained unknown. Here, we report that the seminiferous tubules and rete testis of FoxJ1-Cre;CEP164fl/fl mice exhibit substantial dilation, indicative of dysfunctional multicilia in the EDs. We found that multicilia were hardly detectable in the EDs of FoxJ1-Cre;CEP164fl/fl mice although FoxJ1-positive immature cells were present. Sperm aggregation and agglutination were commonly noticeable in the lumen of the seminiferous tubules and EDs of FoxJ1-Cre;CEP164fl/fl mice. In FoxJ1-Cre;CEP164fl/fl mice, the apical localization of Cby1 and the transition zone marker NPHP1 was severely diminished, suggesting basal body docking defects. TEM analysis of EDs further confirmed basal body accumulation in the cytoplasm of MCCs. Collectively, we conclude that male infertility in FoxJ1-Cre;CEP164fl/fl mice is caused by sperm agglutination and obstruction of EDs due to loss of multicilia. Our study, therefore, unravels an essential role of the distal appendage protein CEP164 in male fertility.


Assuntos
Diferenciação Celular , Cílios/patologia , Epididimo/patologia , Células Epiteliais/patologia , Infertilidade Masculina/patologia , Proteínas dos Microtúbulos/fisiologia , Túbulos Seminíferos/patologia , Animais , Cílios/metabolismo , Epididimo/metabolismo , Células Epiteliais/metabolismo , Infertilidade Masculina/etiologia , Masculino , Camundongos , Camundongos Knockout , Túbulos Seminíferos/metabolismo
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