RESUMO
To facilitate temperature adjustments, the testicles are located outside the body cavity. In most mammals, the temperature of the testes is lower than the body temperature to ensure the normal progression of spermatogenesis. Rising temperatures affect spermatogenesis and eventually lead to a decline in male fertility or even infertility. However, the testes are composed of different cell types, including spermatogonial stem cells (SSCs), spermatocytes, spermatozoa, Leydig cells, and Sertoli cells, which have different cellular responses to heat stress. Recent studies have shown that using different drugs can relieve heat stress-induced reproductive damage by regulating different signaling pathways. Here, we review the mechanisms by which heat stress damages different cells in testes and possible treatments.
Assuntos
Fertilidade , Proteínas de Choque Térmico/metabolismo , Resposta ao Choque Térmico , Temperatura Alta/efeitos adversos , Infertilidade Masculina/metabolismo , Testículo/metabolismo , Animais , Barreira Hematotesticular/metabolismo , Barreira Hematotesticular/patologia , Fertilidade/efeitos dos fármacos , Fármacos para a Fertilidade Masculina/uso terapêutico , Resposta ao Choque Térmico/efeitos dos fármacos , Humanos , Infertilidade Masculina/tratamento farmacológico , Infertilidade Masculina/patologia , Infertilidade Masculina/fisiopatologia , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/patologia , Masculino , Fatores de Risco , Células de Sertoli/metabolismo , Células de Sertoli/patologia , Transdução de Sinais , Espermatócitos/metabolismo , Espermatócitos/patologia , Espermatogônias/metabolismo , Espermatogônias/patologia , Testículo/efeitos dos fármacos , Testículo/patologia , Testículo/fisiopatologiaRESUMO
Resveratrol (RSV) (3,4',5 trihydroxystilbene) is a natural non-flavonoid polyphenol widely present in the Mediterranean diet. In particular, RSV is found in grapes, peanuts, berries, and red wine. Many beneficial effects of this molecule on human health have been reported. In fact, it improves some clinical aspects of various diseases, such as obesity, tumors, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, and diabetes mellitus. However, little is known about the relationship between this compound and male fertility and the few available results are often controversial. Therefore, this review evaluated the effects of RSV on human male fertility and the mechanisms through which this polyphenol could act on human spermatozoa.
Assuntos
Fármacos para a Fertilidade Masculina/química , Fertilidade/efeitos dos fármacos , Polifenóis/química , Resveratrol/química , Arachis/química , Dieta Mediterrânea , Fertilidade/fisiologia , Fármacos para a Fertilidade Masculina/uso terapêutico , Frutas/química , Humanos , Masculino , Polifenóis/uso terapêutico , Resveratrol/uso terapêutico , Espermatozoides/efeitos dos fármacos , Vitis/química , VinhoRESUMO
Background: Male infertility has been on the rise since the past seven decades. Recently, in Libya, bee venom therapy (BVT) has become a popular method among alternative healthcare practitioners for treating male infertility. However, a literature search did not find any published studies that investigated the use of BVT for infertility treatment. Aim: To investigate the effect of bee venom on the male reproductive status through measurements of semen quality parameters and testicular histological changes in adult male mice. Methods: A total of 48 male mice were randomly divided into three experimental groups (which were subdivided into two subgroups with eight mice each) as follows: control, bee venom sting (BVS), and bee venom injection (BVI). The normal control subgroup mice were not subjected to any treatment, while the vehicle control subgroup mice were injected (i.p.) with 200 µl of 0.9% saline solution. In the BVS-treated subgroups, each mouse was stung by one live bee for five times (BVS-5) or seven times (BVS-7) every third day for 2 or 3 weeks. While each mouse in the BVI-treated subgroups received 23 µg/kg in a dose volume of 200 µl BVIs (i.p.) for five times (BVI-5) or seven times (BVI-7) every third day for 15 or 21 days. Results: The findings of this study showed that repeated bee venom treatment by sting or injection to adult male mice resulted in a significant decline in testosterone levels, sperm count, sperm motility, and a very significant increase in the percentage of abnormal sperm morphology; also, there were harmful testicular histological changes in the structural organization of seminiferous tubules and degenerative changes in the germinal epithelium compared to control group. Conclusion: The results of this study provide evidence for the low semen quality and adverse testicular histological changes in male mice treated with bee venom. Hence, there is a desperate need for educating alternative healthcare practitioners and infertile couples about the harmful effects of BVT on reproductive status.
Assuntos
Venenos de Abelha/administração & dosagem , Fármacos para a Fertilidade Masculina/administração & dosagem , Camundongos/fisiologia , Análise do Sêmen , Testículo/efeitos dos fármacos , Animais , Venenos de Abelha/efeitos adversos , Venenos de Abelha/farmacologia , Fármacos para a Fertilidade Masculina/efeitos adversos , Fármacos para a Fertilidade Masculina/farmacologia , Injeções Intraperitoneais/estatística & dados numéricos , Mordeduras e Picadas de Insetos/complicações , Masculino , Distribuição Aleatória , Testículo/anatomia & histologia , Testículo/fisiologiaRESUMO
Contraction of cauda epididymal duct (CE) smooth muscle is one of the very first events of the seminal emission phase of ejaculation. The contraction of CE smooth muscle is governed by a complex interaction of hormones, autacoids, and by the neurotransmitters released from the epididymal intramural nerve endings, and any impairment in the CE smooth muscle contraction has the potential to impair male fertility. Apart the obvious pathophysiological and toxicological importance of CE smooth muscle contraction, modulation of CE contraction has pharmaceutical interest offering a druggable target to development of drugs to improve/impair male fertility. The in vitro contraction experiments constitute a valuable approach to an in-depth evaluation of functional and molecular changes resulting from pathologies or drug exposure. Therefore, this chapter consists in a description of in vitro pharmacological reactivity contractility of the epididymal duct in a controlled medium, maintained at 30 °C of temperature and continuously bubbled with 95% O2 and 5% CO2 to obtain cumulative concentration-response curves that has been fundamental to some of our investigations on epididymal physiology, toxicology, and pharmacology.
Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Epididimo/efeitos dos fármacos , Fármacos para a Fertilidade Masculina/farmacologia , Contração Muscular , Animais , Avaliação Pré-Clínica de Medicamentos/instrumentação , Epididimo/fisiologia , Masculino , Músculo Liso/fisiologia , RatosRESUMO
Obesity is a significant global health and socio-economic challenge, and considered an important risk factor for poor health outcomes including male reproductive dysfunction and infertility. As excess adiposity causes testicular dysfunction and infertility, novel therapeutic strategies require investigation. Nigella sativa (Ns) seed oil and metformin have both demonstrated a potential positive effect on obesity, although both remain poorly investigated in male fertility. Therefore, this study aimed to determine the effect of Ns oil and metformin on total body weight (TBW), mitochondrial membrane potential (MMP), serum testosterone and semen parameters in an obese animal model. Wistar rats (n = 54) were divided into six groups: normal chow (NC), high sugar diet (HSD) only, HSD and saline, HSD and metformin (75 mg/Kg/day), HSD and Ns (200 mg/Kg/day) (NS200), HSD and Ns (400 mg/Kg/day) (NS400). Intervention was force fed for the last 8 weeks of the 14 weeks dietary exposures. Results showed that the HSD increased TBW (P = 0.001) and reduced sperm concentration (P = 0.013) and progressive motility (P = 0.009) compared to the NC group. Metformin, NS200 and NS400 improved TBW (P = 0.035, P = 0.006 and P = 0.005, respectively) and testosterone (P < 0.001) compared to the HSD saline group, where metformin and NS400 improved sperm concentration (P < 0.001 and P = 0.049, respectively) and MMP (P < 0.001). There were no changes in sperm motility and viability for all experimental exposures, although NS400 (P = 0.047) negatively affected sperm viability. Metformin and Ns may be novel treatment options in obesity-induced infertility, although a potential negative impact on viability is cautioned for high dose Ns. These results warrant further investigation of Ns and Metformin for the management of obese infertile males.
Assuntos
Fármacos Antiobesidade/farmacologia , Fármacos para a Fertilidade Masculina/farmacologia , Fertilidade/efeitos dos fármacos , Infertilidade Masculina/prevenção & controle , Metformina/farmacologia , Obesidade/tratamento farmacológico , Óleos de Plantas/farmacologia , Espermatozoides/efeitos dos fármacos , Testosterona/sangue , Animais , Biomarcadores/sangue , Modelos Animais de Doenças , Infertilidade Masculina/sangue , Infertilidade Masculina/patologia , Infertilidade Masculina/fisiopatologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Obesidade/sangue , Obesidade/patologia , Ratos Wistar , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologiaRESUMO
Spermatogenesis process is sensitive to heat stress because the testicular temperature is 2 to 4 °C lower than the core body temperature. The current study aimed to investigate the effects of iron oxide nanoparticles containing curcumin on spermatogenesis in mice induced by long-term scrotal hyperthermia. In this experimental study, 18 mice were equally divided into the following three groups: control, scrotal hyperthermia, and scrotal hyperthermia + curcumin-loaded iron particles (NPs) (240 µL) (mice were treated for 20 days). Hyperthermia was induced by exposure to the temperature of 43 °C for 20 min every other day for 5 weeks. Afterward, the animals were euthanized; sperm samples were collected for sperm parameters analysis, and testis samples were taken for histopathology experiments, evaluation of serum testosterone level, and RNA extraction in order to examine the expression of c-kit, STRA8 and PCNA genes. Our study showed that curcumin-loaded iron particles could notably increase the volume of testis, length of seminiferous tubules, sperm parameters, and stereological parameters (i.e., spermatogonia, primary spermatocyte, round spermatid, and Leydig cells) thereby increasing serum testosterone level; in addition, TUNEL-positive cells showed a significant decrease in curcumin-loaded iron particle group. Thus, based on the obtained results, the expression of c-kit, STRA8, and PCNA genes was significantly increased in treatment groups by curcumin-loaded iron particles compared with scrotal hyperthermia-induced mice. In conclusion, curcumin-loaded iron particles can be considered an alternative treatment for improving the spermatogenesis process in scrotal hyperthermia-induced mice.
Assuntos
Azoospermia/tratamento farmacológico , Curcumina/farmacologia , Portadores de Fármacos , Fármacos para a Fertilidade Masculina/farmacologia , Nanopartículas Magnéticas de Óxido de Ferro/química , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Azoospermia/sangue , Azoospermia/etiologia , Azoospermia/patologia , Biomarcadores/sangue , Curcumina/química , Modelos Animais de Doenças , Composição de Medicamentos , Fármacos para a Fertilidade Masculina/química , Hipertermia Induzida , Masculino , Camundongos , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Espermatozoides/metabolismo , Espermatozoides/patologia , Testículo/metabolismo , Testículo/patologia , Testículo/fisiopatologia , Testosterona/sangue , Fatores de TempoRESUMO
Herbal products with an antioxidant capacity can boost male reproductive functions. The empiric use of Ceratonia siliqua (carob) for its antioxidant properties is common among infertile men in Iran and Turkey. The objective of this study is to investigate the effects of C. siliqua (carob) on semen parameters, oxidative stress markers, and pregnancy rate in a parallel randomized, controlled study. A total of 60 infertile men with oligozoospermia, asthenospermia, and teratospermia were recruited from April 2018 to March 2019. Participants were divided randomly into the following two groups: carob syrup twice a day or vitamin E 100 mg twice a day for 3 months. Semen analysis was performed and hormonal levels and stress oxidative markers were measured in each treatment arm after 3 months. The quality of semen parameters improved in the carob group compared with Vit E semen count (p = 0.04 Cohen's d = .51), morphology (p = 0.001 Cohen's d = .93) and motility parameters (p = 0.002 Cohen's d = .90) were significantly higher in the carob group. No significant difference can be detected in post-treatment hormonal parameters and oxidative markers between groups, except for total antioxidant capacity(TAC) which was higher after post-treatment in carob group. A significantly higher pregnancy rate was found among the carob group. The administration of carob may be an effective agent for the improvement of semen parameters, probably related both to its involvement in the changing of testosterone level and to its antioxidant properties. Nevertheless, additional studies to evaluate the optimal dose and duration of treatment are needed. The trial has been registered in the Iranian Registry of Clinical Trials (Registration number: IRCT20171209037794N1.
Assuntos
Antioxidantes/uso terapêutico , Fabaceae , Fármacos para a Fertilidade Masculina/uso terapêutico , Galactanos/uso terapêutico , Hormônios/sangue , Infertilidade Masculina/tratamento farmacológico , Mananas/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Gomas Vegetais/uso terapêutico , Espermatozoides/efeitos dos fármacos , Vitamina E/uso terapêutico , Adulto , Antioxidantes/efeitos adversos , Antioxidantes/isolamento & purificação , Biomarcadores/sangue , Fabaceae/química , Feminino , Fármacos para a Fertilidade Masculina/efeitos adversos , Fármacos para a Fertilidade Masculina/isolamento & purificação , Hormônio Foliculoestimulante Humano/sangue , Galactanos/efeitos adversos , Galactanos/isolamento & purificação , Humanos , Infertilidade Masculina/sangue , Infertilidade Masculina/diagnóstico , Irã (Geográfico) , Hormônio Luteinizante/sangue , Masculino , Mananas/efeitos adversos , Mananas/isolamento & purificação , Gomas Vegetais/efeitos adversos , Gomas Vegetais/isolamento & purificação , Gravidez , Taxa de Gravidez , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologia , Testosterona/sangue , Fatores de Tempo , Resultado do Tratamento , Vitamina E/efeitos adversosRESUMO
Male infertility has become an important health problem that is primarily caused by testicular dysfunction with abnormal spermatogenesis. In this study, we demonstrated that the neuropeptide, substance P (SP), is essential for spermatogonia proliferation in a seminiferous tubule culture system. In addition, SP (5 nmol/kg) treatment markedly restored spermatogenesis, improved sperm quality, and increased the number of ZBTB16+ or LIN28+ undifferentiated spermatogonia as well as STRA8+ differentiated spermatogonia in a busulfan-induced non-obstructive azoospermic mouse model. Furthermore, 100 nM SP treatment in vitro significantly stimulated the proliferation of GC-1 spg cells (a spermatogonia cell line) via activation of the Erk1/2 signaling pathway. Moreover, the sperm quality and the number of spermatogonia were significantly reduced after treatment with RP67580, a selective NK-1 receptor antagonist, suggesting that SP-NK1R signaling plays an important role in spermatogenesis. Taken together, these results suggest that SP may be a potential therapeutic agent for male infertility by accelerating the restoration of spermatogenesis.
Assuntos
Azoospermia/tratamento farmacológico , Fármacos para a Fertilidade Masculina/farmacologia , Fertilidade/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatogônias/efeitos dos fármacos , Substância P/farmacologia , Animais , Apoptose/efeitos dos fármacos , Azoospermia/induzido quimicamente , Azoospermia/metabolismo , Azoospermia/fisiopatologia , Bussulfano , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Receptores da Neurocinina-1/agonistas , Receptores da Neurocinina-1/metabolismo , Transdução de Sinais , Espermatogônias/metabolismo , Técnicas de Cultura de TecidosRESUMO
When considering empirical medical management (EMT) options for men with unexplained infertility (UI), clomiphene citrate (CC) has been shown to positively influence sperm parameters in hypogonadal men. Unfortunately, the optimal cut point for defining hypogonadism for this patient population has not been established. We hypothesized that hypogonadal men with UI having the lowest serum total testosterone (TT) (<265 ng/dL) would have a significant post-CC improvement in both TT and semen characteristics compared to those in the TT > 264 ng/dL group. We performed our study based on an IRB-approved retrospective chart review of 83 males with UI receiving more than 90 days of 50 mg daily CC. Serum TT and semen characteristics were studied in 83 patients before and in 23 patients after CC treatment. Median TT level increased from 256 ng/dL to 630 ng/dL (p < 0.001, n = 83) and SC increased from 6 ( 106 /ml) to 20 ( 106 /ml) (p < 0.016, n = 23). Overall, our results demonstrated the following: (1) CC treatment at all currently used serum TT cut-points resulted in significant improvement in both TT (p < 0.001) and sperm concentration (p = 0.03). No significant change in post-CC sperm motility or morphology was noted. (2) Correlation and linear regression analyses demonstrated that CC treatment significantly increased TT in 96% (22 of 23) of patients, and (3) when grouped as two cohorts (≤264 and >264 ng/dL), sperm concentration and TT improved 2.3 to 2.6-fold (p < 0.001) and 1.45 to 2.5-fold (p < 0.01) respectively. Thus, for hypogonadal men with UI, CC significantly improved TT and sperm concentration regardless of pre-treatment, baseline serum TT level. For this reason, CC treatment should be considered in men with UI having a TT < 400 ng/dL.
Assuntos
Clomifeno/uso terapêutico , Fármacos para a Fertilidade Masculina/uso terapêutico , Hipogonadismo/tratamento farmacológico , Infertilidade Masculina/tratamento farmacológico , Espermatogênese/efeitos dos fármacos , Testosterona/sangue , Adulto , Biomarcadores/sangue , Humanos , Hipogonadismo/complicações , Hipogonadismo/diagnóstico , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/etiologia , Masculino , Estudos Retrospectivos , Contagem de Espermatozoides , Fatores de Tempo , Resultado do TratamentoRESUMO
Some amino acids can protect mammalian sperm cells against oxidation during thermal stress caused by freezing/thawing. Thus, the objective was to evaluate the protective action of the association of the amino acids L-proline (Pro) and L-glutamine (Glu) against the cryoinjury caused to sheep sperm after cryopreservation. Eight ejaculates were collected from four sheep (n=32) and diluted in Tris-Egg Yolk-Glycerol until the final concentration of 200 x106 sptz/mL and kept in a water bath at 32 °C. The amino acids were added as follows: control (without adding amino acids), Pro+Glu 1 (100 µM Pro + 500 µM Glu), Pro+Glu 2 (300 µMPro + 1000 µM Glu), Pro+Glu 3 (500 µM Pro + 1500 µM Glu) and Pro+Glu 4 (700 µM Pro + 2000 µM Glu). Afterwards, the semen was cooled to 5 °C for 2 h, after that period, filled in 0.5 mL straws and then placed under liquid nitrogen vapor (N2L), 8 cm from the liquid sheet for 15min, and then immersed on the N2L. The samples were analyzed for sperm motility, plasma membrane and acrosomal membrane integrity, mitochondrial activity and binding test. The variables were subjected to the normality tests (Lilliefors test) and homoscedasticity tests (Cochran and Bartlett test), afterwards the variables of normal distribution were subjected to analysis of variance and the means compared by the Tukey test with a significance level of 5%. The Pro+Glu 3 group exhibited sperm with a greater (P<0.05) motility after thawing. In addition, the highest percentage of plasma and acrosomal membrane integrity were obtained using Pro+Glu 1, Pro+Glu 2 and Pro+Glu 3; and Pro+Glu 2 and Pro+Glu 3, respectively. Amino acids also kept mitochondrial activity high compared to the control, with Pro+Glu 3 resulting in greater activity (P<0.05). Sperm viability was higher (P<0.05) with the use of Pro+Glu 2 and Pro+Glu 3 than in the control. The number of sperm that showed the ability to bind to the egg yolk perivitelline membrane was higher (P<0.05) in semen treated with amino acids. It is concluded that the addition of synthetic amino acids in the semen of sheep before cryopreservation improves sperm quality and fertilization potential and can thus be added in cryopreservation protocols.
Alguns aminoácidos podem proteger as células espermáticas de mamíferos contra a oxidação durante o estresse térmico causado na congelação/descongelação. Dessa forma, objetivou-se avaliar a ação protetora da associação dos aminoácidos L-prolina (Pro) e L-glutamina (Glu) contra as crioinjúrias causadas aos espermatozoides de ovino após a criopreservação. Foram coletados oito ejaculados de quatro carneiros (n=32) e diluídos em Tris-Gema de ovo-Glicerol até a concentração final de 200 x106 sptz/mL e, mantidos em banho maria a 32 °C. Os aminoácidos foram adicionados da seguinte forma: controle (sem adição de aminoácidos), Pro+Glu 1 (100 µM Pro + 500 µM Glu), Pro+Glu 2 (300 µM Pro + 1000 µM Glu), Pro+Glu 3 (500 µM Pro + 1500 µM Glu) e Pro+Glu 4 (700 µM Pro + 2000 µM Glu). Depois, o sêmen foi resfriado a 5 °C por 2 h, após esse período, envasado em palhetas de 0,5 mL e então acondicionado sob vapor de nitrogênio líquido (N2L), a 8 cm da lâmina líquida por 15 min, e depois imersos no N2L. As amostras foram analisadas quanto à motilidade espermática, integridade da membrana plasmática e da membrana acrossomal, atividade mitocondrial e teste de ligação. As variáveis foram submetidas aos testes de normalidade (Teste de Lilliefors) e homocedacidade (Teste de Cochran e Bartlett), posteriormente as variáveis de distribuição normal foram submetidas à análise de variância e as médias comparadas pelo teste de Tukey com nível de significância de 5%. O grupo Pro+Glu 3 exibiu espermatozoides com uma maior (P<0,05) motilidade após o descongelamento. Além disso o maior percentual de integridade da membrana plasmatica e acrossomal foram obtidos utilizando Pro+Glu 1, Pro+Glu 2 e Pro+Glu 3; e Pro+Glu 2 e Pro+Glu 3, respectivamente. Os aminoácidos também mantiveram alta a atividade mitocondrial em comparação com o controle, com Pro+Glu 3 resultando numa maior atividade (P<0,05). A viabilidade dos espermatozoides foi maior (P<0,05) com o uso de Pro+Glu 2 e Pro+Glu 3 do que no controle. O número de espermatozoides que apresentaram à capacidade de ligação a membrana perivitelina da gema de ovo foi maior (P<0,05) no sêmen tratado com aminoácidos. Conclui-se que, a adição dos aminoácidos sintéticos no sêmen de ovinos antes da criopreservação melhora a qualidade espermática e o potencial fecundante, podendo assim serem adicionados em protocolos de criopreservação.
Assuntos
Animais , Espermatozoides/efeitos dos fármacos , Ovinos/genética , Criopreservação/veterinária , Análise do Sêmen/veterinária , Fertilidade/efeitos dos fármacos , Fármacos para a Fertilidade Masculina/administração & dosagem , Prolina/administração & dosagem , Glutamina/administração & dosagemRESUMO
Background Infertility remains a highly prevalent global condition in the second decade of the new millennium. Reproductive hormones determine sperm quality as they initiate and maintain spermatogenesis. Hormonal imbalance can cause abnormal sperm quality that can be treated by hormonal replacement therapy. Objective To assess the relationship between sperm quality and male reproductive hormones among male partners with fertility complications attending CHUB. Methods The study was a descriptive cross-sectional, and a convenient sampling strategy was used to recruit subjects at CHUB. Sixty-two male subjects with fertility complications provided both semen and blood sample to analyze sperm quality and reproductive hormones. Descriptive statistics were used to analyze data. Results Both FSH and LH showed a strong negative correlation with sperm count which is more profound with FSH (r= -0.722) than LH (r= -0.545). Testosterone showed a strong positive correlation with sperm count (r= 0.712). FSH and LH showed a negative correlation with sperm motility which is more profound in FSH (r= - 0.312) than LH (r= -0.302). Testosterone also showed a positive correlation with sperm motility (r= 0.360). Conclusion Our study found a correlation between sperm quality and male reproductive hormones. We further suggest other studies to investigate predictive power of male reproductive hormones.
Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Fármacos para a Fertilidade MasculinaRESUMO
BACKGROUND: In Hong Kong, one of six couples is affected by subfertility problems. Male infertility contributes to half of the infertility cases. In male infertility, there is no effective treatment for patients with idiopathic infertility/poor semen parameters. Recent meta-analysis results suggest that a traditional Chinese medicine (TCM) formula - Wuzi Yanzong pill - showed a curative effect on male fertility. However, the heterogeneity of the studies could not draw a definitive conclusion on the therapeutic effect of this formula. The aim of this study is to conduct a well-designed randomized controlled trial to investigate the effect of TCM formula Wuzi Yanzong pill on improving semen qualities in men with suboptimal parameters. METHODS: This study is a double-blinded, randomized placebo-controlled trial conducted in a public hospital in Hong Kong. Participants will be randomized, using computer-generated random numbers, with a 1:1 ratio to either the Wuzi Yanzong pill formula group or the placebo group. Both groups will be administered the drugs for 12 weeks. Participants will have a total of four visits for their semen and blood assessments for a 6-month period, and we will follow up for another 6 months to record their conception outcome. The primary outcome is to compare the total motile sperm count, natural conception rate, and pregnancy outcome to those under placebo treatment. Secondary objectives are sperm functions and assisted reproductive technology outcome. DISCUSSION: To date, there are no studies using the disclosed Wuzi Yanzong formula or double-blinded, randomized trials. The Wuzi Yanzong TCM formula may provide a good clinical solution for subfertile males for which contemporary western medicine has no cure. Therefore, a well-designed randomized trial for evaluating the effect of Wuzi Yanzong TCM formula is urgently needed. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR-INR-17010790 . Registered on 27 February 2017. Centre for Clinical Research and Biostatistics - Clinical Trials Registry, CUHK_CCRB00548 . Registered on 27 February 2017.
Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Fármacos para a Fertilidade Masculina/administração & dosagem , Fertilidade/efeitos dos fármacos , Infertilidade Masculina/tratamento farmacológico , Sêmen/efeitos dos fármacos , Administração Oral , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Estudos de Equivalência como Asunto , Fármacos para a Fertilidade Masculina/efeitos adversos , Hong Kong , Humanos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/fisiopatologia , Masculino , Estudos Prospectivos , Análise do Sêmen , Comprimidos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Nigerian Cannabis sativa (hemp) causes male gonadotoxicity by inducing hyperprolactinemia, down-regulation of hypothalamic-pituitary-testicular axis, and oxidative stress. Benin republic hemp has been preferred by illicit users in Nigeria but its effect on male fertility is not understood. This study determined and compared the compositions of Benin republic hemp ethanol extract (BHE) and Nigerian hemp. The effects of BHE on semen parameters, reproductive hormones, and anti-oxidant status, and the possibility of bromocriptine (prolactin inhibitor) to abolish hemp-induced toxicities in rats were also investigated. METHODS: Thirty-six male Wistar rats were blindly randomized into 6 oral treatment groups (n = 6 each). Groups I (control) and II received normal saline and bromocriptine (3 mg/kg) respectively. Groups III and IV received 2 mg/kg of BHE alone and in combination with bromocriptine respectively, while groups V and VI received 10 mg/kg BHE alone and in combination with bromocriptine respectively. Comparisons among the groups were done by one-way analysis of variance, followed by post-hoc Tukey multiple comparison test. Statistical significance was considered at p < 0.05. RESULTS: The BHE has no cannabichromene and tetrahydrocannabinol but a very small quantity of cannabinol and higher quantity of fatty acids when compared to Nigerian hemp. Both doses of BHE increased sperm count, morphology and viability but not motility. Co-administration of BHE with bromocriptine lowered sperm count but increased sperm morphology and viability. Bromocriptine and/or BHE caused reduction in the plasma prolactin level, increase in the plasma superoxide dismutase activity, but no significant change in the plasma gonadotropin releasing hormone, follicle stimulating hormone (except for the increase in rats that received bromocriptine+ 10 mg/kg BHE), luteinizing hormone, estradiol, malondialdehyde and glutathione peroxidase. The 10 mg/kg BHE or bromocriptine+BHE (both doses) increased total anti-oxidant capacity and catalase. CONCLUSIONS: The BHE improves semen parameters by reducing plasma prolactin and enhancing plasma anti-oxidant status. Its pro-fertility potential might be associated with its deficiency in the widely known gonadotoxic phytocannabinoids.
Assuntos
Antioxidantes/metabolismo , Canabinoides/análise , Cannabis/química , Dronabinol/análise , Fármacos para a Fertilidade Masculina/farmacologia , Extratos Vegetais/farmacologia , Prolactina/metabolismo , Sêmen/efeitos dos fármacos , Animais , Canabinoides/farmacologia , Dronabinol/farmacologia , Fertilidade/efeitos dos fármacos , Fármacos para a Fertilidade Masculina/análise , Masculino , Extratos Vegetais/análise , Ratos , Sêmen/metabolismoRESUMO
Conventional in vitro fertilization has not yet been implemented in the equine species. One of the main reasons has been the inability to develop a culture medium and incubation conditions supporting high levels of stallion sperm capacitation and hyperactivation in vitro. Although different culture media have been used for this purpose, human tubal fluid (HTF) medium, widely used in the manipulation of human and mice gametes, has not been reported so far in stallion sperm culture. The first part of this study aimed to compare HTF and Whitten's media on different stallion sperm quality and capacitation variables. Additionally, the effect of procaine, aminopyridine and caffeine in both media was evaluated on sperm motility parameters at different incubation times. Integrity and destabilization of the plasma membrane were evaluated by merocyanine 540/SYTOX Green (MC540), mitochondrial membrane potential (∆Ψm) using tetramethylrhodamine methyl ester perchlorate (TMRM), acrosome membrane integrity by PNA/FITC and tyrosine phosphorylation by P-tyrosine mouse mAb conjugated to Alexa Fluor® by flow cytometry. Motility parameters were evaluated using the integrated semen analysis system (ISAS®). We found no differences between Whitten's and HTF media and incubation time in terms of sperm viability, uninduced acrosome membrane damage or mitochondrial membrane potential at 30- and 120-min incubation. Membrane fluidity (MC540) increased in both media at 30- and 120-min incubation compared to noncapacitating conditions. Similarly, tyrosine phosphorylation increased in both media in capacitating conditions at 2- and 4-hr incubation compared to noncapacitating conditions. Although procaine showed the best result in terms of sperm hyperactivated motility in both media, aminopyridine also showed parameters consistent with the hyperactivation including an increase in curvilinear velocity and decrease in straightness. In conclusion, HTF medium and aminopyridine equally support capacitation-related parameters in stallion sperm.
Assuntos
Meios de Cultura/farmacologia , Fármacos para a Fertilidade Masculina/farmacologia , Cavalos , Análise do Sêmen/veterinária , Capacitação Espermática/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacos , Reação Acrossômica/efeitos dos fármacos , Aminopiridinas/farmacologia , Animais , Cafeína/farmacologia , Fertilização in vitro/veterinária , Fluoresceínas/farmacologia , Masculino , Potencial da Membrana Mitocondrial , Aglutinina de Amendoim/farmacologia , Fosforilação , Procaína/farmacologia , Sêmen/efeitos dos fármacos , Análise do Sêmen/métodos , Espermatozoides/efeitos dos fármacosRESUMO
The management of nonobstructive azoospermia in the context of fertility treatment is discussed. This document replaces the ASRM document titled "Evaluation of azoospermia," last published in 2008.
Assuntos
Azoospermia/terapia , Infertilidade Masculina/terapia , Técnicas de Reprodução Assistida/normas , Azoospermia/complicações , Azoospermia/diagnóstico , Azoospermia/genética , Consenso , Prova Pericial , Fármacos para a Fertilidade Masculina/uso terapêutico , Testes Genéticos/normas , Humanos , Hipogonadismo/diagnóstico , Hipogonadismo/etiologia , Hipogonadismo/terapia , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/etiologia , Infertilidade Masculina/genética , Masculino , Técnicas de Diagnóstico Molecular/normas , Planejamento de Assistência ao Paciente/normas , Recuperação Espermática/normasRESUMO
INTRODUCTION: One of the principles of contemporary management of male infertility is a correction of oxidative stress, replenishment of vitamins, microelements and low molecular weight peptides, and therefore multicomponent biologically active complexes, one of which is the Speroton, are widely used. AIM: To investigate the effect of the Speroton complex on the functional sperm characteristics and fertility of men with pathozoospermia. MATERIALS AND METHODS: We examined 60 men aged from 25 to 40 years old with male infertility against the background of various spermatogenesis disorders. Patients were randomized into two groups of 30 people each. A control group (CG) underwent general therapy. In the study group (SG) patients received a combination of general therapy and Speroton. The study participants were subsequently examined at four study visits. The parameters of the spermogram were assessed according to WHO criteria: sperm concentration, sperm motility, the total number of sperm with normal morphology, ejaculate volume and ejaculate liquefaction time, the level of fructose and zinc, and cases of pregnancy in the partner. RESULTS: The use of the Speroton complex resulted in a 10% increase in ejaculate volume, a 15.6% increase in sperm concentration, and a 32% reduction in liquefaction time. The proportion of progressively motile spermatozoa (grade A + B) showed a 2.6 fold increase due to activation of grade C spermatozoa. This, in our opinion, may be associated with a change in the ejaculate enzyme composition, which is indirectly confirmed by a 1.6 fold increase in the level of fructose and 15% increase in the amount of zinc in sperm biochemistry. The effectiveness of therapy in SG patients is also confirmed by 4 cases of spontaneous pregnancy, which occurred against a background of qualitative changes in sperm count. CONCLUSION: The use of Speroton increases the sperm concentration and motility in patients with male factor infertility, and an increase in the number of spontaneous pregnancies in their partners.
Assuntos
Fármacos para a Fertilidade Masculina/uso terapêutico , Fertilidade/efeitos dos fármacos , Infertilidade Masculina/tratamento farmacológico , Espermatozoides/efeitos dos fármacos , Tocoferóis/uso terapêutico , Adulto , Humanos , Masculino , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/citologia , Resultado do TratamentoRESUMO
Membrane integrity is essential in maintaining sperm viability, signaling, and motility, which are essential for fertilization. Sperm are highly susceptible to oxidative stress, as they are rich in sensitive polyunsaturated fatty acids (PUFA), and are unable to synthesize and repair many essential membrane constituents. Because of this, sperm cellular membranes are important targets of this process. Membrane Lipid Replacement (MLR) with glycerophospholipid mixtures (GPL) has been shown to ameliorate oxidative stress in cells, restore their cellular membranes, and prevent loss of function. Therefore, we tested the effects of MLR on sperm by tracking and monitoring GPL incorporation into their membrane systems and studying their effects on sperm motility and viability under different experimental conditions. Incubation of sperm with mixtures of exogenous, unoxidized GPL results in their incorporation into sperm membranes, as shown by the use of fluorescent dyes attached to GPL. The percent overall (total) sperm motility was increased from 52±2.5% to 68±1.34% after adding GPL to the incubation media, and overall sperm motility was recovered from 7±2% after H2O2 treatment to 58±2.5%)(n = 8, p<0.01) by the incorporation of GPL into sperm membranes. When sperm were exposed to H2O2, the mitochondrial inner membrane potential (MIMP), monitored using the MIMP tracker dye JC-1 in flow cytometry, diminished, whereas the addition of GPL prevented the decrease in MIMP. Confocal microscopy with Rhodamine-123 and JC-1 confirmed the mitochondrial localization of the dyes. We conclude that incubation of human sperm with glycerolphospholipids into the membranes of sperm improves sperm viability, motility, and resistance to oxidizing agents like H2O2. This suggests that human sperm might be useful to test innovative new treatments like MLR, since such treatments could improve fertility when it is adversely affected by increased oxidative stress.
Assuntos
Glicerofosfolipídeos/química , Glicerofosfolipídeos/farmacologia , Micelas , Estresse Oxidativo/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/citologia , Espermatozoides/efeitos dos fármacos , Adulto , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Técnicas de Cultura , Fármacos para a Fertilidade Masculina/química , Fármacos para a Fertilidade Masculina/farmacologia , Glicerofosfolipídeos/metabolismo , Humanos , Masculino , Espermatozoides/metabolismoRESUMO
Sperm cells are highly sensitive to reactive oxygen species (ROS), which are produced during cellular oxidation. In normal cell biology, ROS levels increase with a decreasing antioxidant response, resulting in oxidative stress which threatens sperm biology. Oxidative stress has numerous effects, including increased apoptosis, reduced motion parameters, and reduced sperm integrity. In this regard, green tea polyphenols (GrTPs) have been reported to possess properties that may increase the quality of male and female gametes, mostly via the capability of catechins to reduce ROS production. GrTPs have antioxidant properties that improve major semen parameters, such as sperm concentration, motility, morphology, DNA damage, fertility rate, and gamete quality. These unique properties of green tea catechins could improve reproductive health and represent an important study area. This exploratory review discusses the therapeutic effects of GrTPs against infertility, their possible mechanisms of action, and recommended supportive therapy for improving fertility in humans and in animals.
Assuntos
Antioxidantes/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Fármacos para a Fertilidade Masculina/uso terapêutico , Fertilidade/efeitos dos fármacos , Infertilidade Feminina/tratamento farmacológico , Infertilidade Masculina/tratamento farmacológico , Polifenóis/uso terapêutico , Saúde Reprodutiva , Chá , Animais , Antioxidantes/isolamento & purificação , Feminino , Humanos , Infertilidade Feminina/metabolismo , Infertilidade Feminina/patologia , Infertilidade Feminina/fisiopatologia , Infertilidade Masculina/metabolismo , Infertilidade Masculina/patologia , Infertilidade Masculina/fisiopatologia , Masculino , Óvulo/efeitos dos fármacos , Óvulo/metabolismo , Óvulo/patologia , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/isolamento & purificação , Gravidez , Fatores de Risco , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologia , Chá/químicaRESUMO
Sexual dysfunction is a poorly understood condition that affects up to one-third of men around the world. Existing treatments that target the periphery do not work for all men. Previous studies have shown that central melanocortins, which are released by pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus, can lead to male erection and increased libido. Several studies specifically implicate the melanocortin 4 receptor (MC4R) in the central control of sexual function, but the specific neural circuitry involved is unknown. We hypothesized that single-minded homolog 1 (Sim1) neurons play an important role in the melanocortin-mediated regulation of male sexual behavior. To test this hypothesis, we examined the sexual behavior of mice expressing MC4R only on Sim1-positive neurons (tbMC4Rsim1 mice) in comparison with tbMC4R null mice and wild-type controls. In tbMC4Rsim1 mice, MC4R reexpression was found in the medial amygdala and paraventricular nucleus of the hypothalamus. These mice were paired with sexually experienced females, and their sexual function and behavior was scored based on mounting, intromission, and ejaculation. tbMC4R null mice showed a longer latency to mount, a reduced intromission efficiency, and an inability to reach ejaculation. Expression of MC4R only on Sim1 neurons reversed the sexual deficits seen in tbMC4R null mice. This study implicates melanocortin signaling via the MC4R on Sim1 neurons in the central control of male sexual behavior.
Assuntos
Tonsila do Cerebelo/metabolismo , Núcleo Arqueado do Hipotálamo/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Infertilidade Masculina/metabolismo , Neurônios/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Receptor Tipo 4 de Melanocortina/metabolismo , Proteínas Repressoras/metabolismo , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/patologia , Animais , Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Núcleo Arqueado do Hipotálamo/patologia , Copulação/efeitos dos fármacos , Cruzamentos Genéticos , Fármacos para a Fertilidade Masculina/administração & dosagem , Fármacos para a Fertilidade Masculina/uso terapêutico , Heterozigoto , Infertilidade Masculina/tratamento farmacológico , Infertilidade Masculina/patologia , Injeções Intraventriculares , Masculino , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Especificidade de Órgãos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/patologia , Distribuição Aleatória , Receptor Tipo 4 de Melanocortina/genética , Comportamento Sexual Animal/efeitos dos fármacos , alfa-MSH/administração & dosagem , alfa-MSH/uso terapêuticoRESUMO
Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder amongst women of reproductive age, which is characterized by reproductive and cardiometabolic disturbances with long-term health repercussions. Insulin resistance (IR), impaired glucose tolerance, type 2 diabetes mellitus (DM2), obesity and dyslipidemia occur more in women with PCOS than in age-comparable women without PCOS. Long term data regarding risks or benefits of medical intervention for metabolic dysfunction of PCOS are lacking. Therapies, such as oral contraceptives (OCPs) and anti-androgenic medications used to manage the reproductive manifestations of PCOS, may themselves be the cause of cardiometabolic perturbations. Hence, strategies regarding the management of reproductive issues in PCOS encompass a patient-specific tailored approach. Factors that influence the cardiometabolic side effects arising during treatment of the reproductive manifestations of PCOS (hirsutism/anovulation) are also discussed in this paper in order to build future strategies to minimize the overall cardiometabolic risk.