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迟发性性腺功能减退症与骨化二醇的关系

Asian Journal of Andrology 2015年第2期17卷 236-238,I0008页

作者： Carlo Foresta Aldo E Calogero Francesco Lombardo Andrea Lenzi Alberto Ferlin Department of Medicine and Centre for Human Reproduction Pathology University of Padova Padova 35128 Italy Department of Medical and Pediatric Sciences Section of Endocrinology Andrology and Internal Medicine University of Catania Catania 95123 Italy Department of Experimental Medicine Section of Medical Pathophysiology and Endocrinology Sapienza University of Rome Rome 00185 Italy

男性迟发性性腺功能减退症是指具有血清睾酮（T）水平降低和典型临床症状的综合征。而血清睾酮浓度是否总能真实反应Leydig细胞的功能目前仍不确定。轻度睾丸改变只有通过检测额外的生化标记物如黄体生成素（LH）和25．羟维生素D才能确... 详细信息

男性迟发性性腺功能减退症是指具有血清睾酮（T）水平降低和典型临床症状的综合征。而血清睾酮浓度是否总能真实反应Leydig细胞的功能目前仍不确定。轻度睾丸改变只有通过检测额外的生化标记物如黄体生成素（LH）和25．羟维生素D才能确诊。这些标记物可以帮助诊断称之为“亚临床”型的性腺功能减退（血清睾酮正常，LH升高）。性腺功能减退患者通常由于睾丸中CYP2Rt羟化酶受损而具有较低水平的25．羟维生素D。然而，目前仍无证据阐释维生素D3亦或骨化二醇是治疗此类病人的最佳选择。因此我们分析了26位具有典型性腺功能减退患者（总T[TT]〈12nmol 1^-1，LH≥8IU 1^-1）及46位亚临床型性腺功能减退患者（TT≥12nmol 1^-1，LH≥8IU 1^-1）以及低25-羟维生素D患者（〈50nmol 1^-1）。其中20名患者接受每周5000IU的维生素D3治疗，46名患者接受每周4000IU的骨化二醇治疗。治疗3个月后，患者25-羟维生素D及甲状旁腺激素升高。在两组患者中（原发型16人，亚临床型30人）补充骨化二醇可以显著提高25-羟维生素D水平并显著降低甲状旁腺激素水平，而补充维生素D3的患者，其25-羟维生素D和甲状旁腺激素水平并无明显变化。本研究首次阐述服用骨化二醇而非维生素D3，可以提高男性迟发性性腺功能减退患者25-羟维生素D水平。

关键词：胰岛素样因子3 迟发性性腺功能减退症男性性腺功能减退症睾酮维生素D

Sperm glyceraldehyde 3-phosphate dehydrogenase gene expression in asthenozoospermic spermatozoa

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Asian Journal of Andrology 2017年第4期19卷 409-413页

作者： Donatella Paoli Marianna Pelloni Mariagrazia Gallo Giulia Coltrinari Francesco Lombardo Andrea Lenzi Loredana Gandini Laboratory of Seminology - Sperm Bank Department of Experimental Medicine University of Rome 'La Sapienza' 00161 Rome Italy

It has been suggested that the energy required for sperm motility is produced by oxidative phosphorylation while glycolysis seems to be an important source for ATP transmission along the flagellum. Some studies have investigated the chemical and kinetic properties of the enzyme glyceraldehyde 3-phosphate dehydrogenase to identify any changes in the regulation of glycolysis and sperm motility. In contrast, there are few studies analyzing the genetic basis of hypokinesis. For this reason, we investigated the glyceraldehyde 3-phosphate dehydrogenase gene in human sperm to evaluate whether asthenozoospermia was correlated with any changes in its expression. Semen examination and glyceraldehyde 3-phosphate dehydrogenase gene expression studies were carried out on 116 semen samples divided into two groups - Group A consisted of 58 normokinetic samples and Group B of 58 hypokinetic samples. Total RNA was extracted from spermatozoa, and real-time PCR quantification of mRNA was carried out using specific primers and probes. The expression profiles for the Groups A and B were very similar. The mean delta Ct was as follows - Group A, 5.79 ＋ 1.04; Group B, 5.47 ＋ 1.27. Our study shows that in human sperm, there is no difference in glyceraldehyde 3-phosphate dehydrogenase gene expression between samples with impaired motility and samples with normal kinetics. We believe that this study could help in the understanding of the molecular mechanisms of sperm kinetics, suggesting that hypomotility may be due to a possible posttranscriptional impairment of the control mechanism, such as mRNA splicing, or to posttranslational changes.

关键词： adenosine-5＇-triphosphate gene expression sperm glyceraldehyde 3-phosphate dehydrogenase sperm motility

Severe male factor in in vitro fertilization:definition,prevalence,and treatment.An update

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Asian Journal of Andrology 2022年第2期24卷 125-134页

作者： Rossella Mazzilli Alberto Vaiarelli Lisa Dovere Danilo Cimadomo NicolòUbaldi Susanna Ferrero Laura Rienzi Francesco Lombardo Andrea Lenzi Herman Tournaye Filippo Maria Ubaldi Clinica Valle Giulia GeneraLife IVF CentersVia G.De NotarisRome 2B 00197Italy Department of Clinical and Molecular Medicine University of Rome“Sapienza”Via di Grottarossa 1035Rome 00189Italy Catholic University of the Sacred Heart Via della Pineta Sacchetti 217Rome 00168Italy Department of Experimental Medicine “Sapienza”University of RomeViale del Policlinico 155Rome 00161Italy Centre for Reproductive Medicine Free University Brussels(UZ Brussel)Brussels 1090Belgium

Infertility affects 10%–15%of couples worldwide.Of all infertility cases,20%–70%are due to male factors.In the past,men with severe male factor(SMF)were considered sterile.Nevertheless,the development of intracytoplasmic sperm injection(ICSI)drastically modified this scenario.The advances in assisted reproductive technology(ART),specifically regarding surgical sperm retrieval procedures,allowed the efficacious treatment of these conditions.Yet,before undergoing ICSI,male factor infertility requires careful evaluation of clinical and lifestyle behavior together with medical treatment.Epidemiologically speaking,women whose male partner is azoospermic tend to be younger and with a better ovarian reserve.These couples,in fact,are proposed ART earlier in their life,and for this reason,their ovarian response after stimulation is generally good.Furthermore,in younger couples,azoospermia can be partially compensated by the efficient ovarian response,resulting in an acceptable fertility rate following in vitro fertilization(IVF)techniques.Conversely,when azoospermia is associated with a reduced ovarian reserve and/or advanced maternal age,the treatment becomes more challenging,with a consequent reduction in IVF outcomes.Nonetheless,azoospermia seems to impair neither the euploidy rate at the blastocyst stage nor the implantation of euploid blastocysts.Based on the current knowledge,the assessment of male infertility factors should involve:(1)evaluation–to diagnose and quantify seminologic alterations;(2)potentiality–to determine the real possibilities to improve sperm parameters and/or retrieve spermatozoa;(3)time–to consider the available“treatment window”,based on maternal age and ovarian reserve.This review represents an update of the definition,prevalence,causes,and treatment of SMF in a modern ART clinic.

关键词： azoospermia in vitro fertilization infertility intracytoplasmic sperm injection severe male factor sperm

Inhibin B:are modified ranges needed for orchiectomised testicular cancer patients?

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Asian Journal of Andrology 2019年第4期21卷 332-336页

作者： Alessandra Petrozzi Francesco Pallotti Marianna Pelloni Antonella Anzuini Antonio Francesco Radicioni Andrea Lenzi Donatella Paoli Francesco Lombardo Laboratory of Seminology Sperm Bank "Loredana Gandini" Department of Experimental Medicine Medical Pathophysiology Section"Sapienza" University of Rome Rome 00161 Italy Hormone Laboratory Department of Experimental Medicine Medical Pathophysiology Section"Sapienza" University of Rome Rome 00161 Italy

Inhibin B is a gon adal horm one that down regulates the pituitary production of follicle-stimulati ng horm one (FSH). In recent years, inhibin B has proved to be an excellent marker of spermatogenesis and even a predictive factor for the recovery of fertility in patients undergoing orchiectomy and antineoplastic treatments. We propose to study inhibin B levels in orchiectomised testicular cancer patients, in order to identify a minimum value representative of normal semen quality. This retrospective study evaluates horm onal and semen parameters of 290 no rmozoospermic patie nts atte nding the Laboratory of Semi no logy - Sperm Bank "Loredana Gandini"(Rome, Italy) for cryopreservation of seminal fluid following a diagnosis of testicular cancer (TC group) and 117 healthy, normozoospermic men as a control group (CTR group). The percentile distribution of gonadotropin and inhibin B values in the TC and CTR groups was analyzed. There was a statistically significant differenee between the two groups in the levels of all hormones (P ≤ 0.001) and in all semen parameters (P 95^th percentile of CTR group. Orchiectomised patients for testicular cancer presented inhibin B levels lower than healthy patients, despite normozoospermia. Our study revealed the poor sensitivity of the current inhibin B reference range when applied to monorchidic patients, suggesting the need to establish more representative ranges to enable more appropriate counseling in relation to the patienfs new endocrine condition.

关键词： inhibin B orchiectomy referenee range testicular cancer

Effects of percutaneous varicocele repair on testicular volume:results from a 12-month follow-up

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Asian Journal of Andrology 2019年第4期21卷 408-412页

作者： andrea Sansone Danilo Alunni Fegatelli Carlotta Pozza Giorgio Fattorini Rosa Lauretta Marianna Minnetti Francesco Romanelli Pierleone Lucatelli Mario Corona Mario Bezzi Francesco Lombardo Andrea Lenzi Daniele Gianfrilli Departme nt of Experime ntal Medici ne Sa pie nza Un iversity of Rome Rome 00161 Italy Department of Public Health and In fectious Diseases Sapienza University of Rome Rome 00161 Italy Unit of Endocrinology Regina Elena National Cancer Institute Rome 00144 Italy Vascular and Interventional Radiology Unit Department of Radiological Oncological and Anatomo-Pathological Sciences Sapienza-University of Rome Rome 00161 Italy

Varicocele is a comm on fin ding in men. Varicocele correcti on has bee n advocated for young patients with testicular hypotrophy, but there is a lack of morphofunctional follow-up data. We assessed whether percutaneous treatment of left varicocele is associated with testicular "catch-up growth" in the following 12 months by retrospectively reviewing data from an electronic database of 10 656 patients followed up in our clinic between 2006 and 2016. We selected all young adults (20% difference between left and right testicular volume at baseline, was observed in 26 (22.8%) men. Participants with LTH (mean±s.d.: 14.5 ± 2.7 ml) had lower baseline testicular volume compared to those without LTH (mean±s.d.: 15.7 ± 3.8 ml;P= 0.032). Repeated measures mixed models showed a sign ifica nt in teraction betwee n LTH and time posttreatme nt when correcting for baseli ne left testicular volume (β= 0.114, 95% confidence interval [Cl]: 0.018-0.210, P=0.020), resulting in a catch-up growth of up to 1.37 ml per year (95% Cl: 0.221- 2.516). Age at intervention was also associated with reduced testicular volume (-0.072 ml per year, 95% Cl:-0.135--0.009;P = 0.024). Percutaneous treatment of left varicocele in young adults with LTH can result in catch-up growth over 1 year of follow-up. The reproductive and psychological implicati ons of these findings n eed to be confirmed in Ion ger and larger prospective studies.

关键词： catch-up growth percutaneous treatment testicular hypotrophy testicular ultrasound testicular volume varicocele young adults

The role of antioxidant therapy in the treatment of male infertility： an overview

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Asian Journal of Andrology 2011年第5期13卷 690-697页

作者： Francesco Lombardo andrea Sansone Francesco Romanelli DonateUa Paoli Loredana Gandiniand Andrea Lenzi Department of Experimental Medicine Policlinico ＇Umberto I＇ University of Rome ＇La Sapienza＇ Rome 00161 Italy

In recent years, many studies have focused on the effect of oxidative stress, reactive oxygen species （ROS） and antioxidants on the male eproductive system. Under physiological conditions, sperm produces small amounts of ROS, which are needed for fertilisation, acrosome reaction and capacitation. However, if an increased production of ROS is not associated with a similar increase in scavenging systems, peroxidative damage of the sperm plasma membrane and loss of DNA integrity typically occur, which leads to cell death and reduced fertility. Furthermore, since there is no linear correlation between sperm quality and pregnancy rates, an improvement in semen parameters should not be the sole outcome considered in studies of antioxidant therapies. A definitive conclusion regarding the benefit of these therapies is difficult to obtain, as most of the previous studies lacked control groups, considered different antioxidants in different combinations and doses, or did not evaluate pregnancy rates in previously infertile couples. Even if beneficial effects were reported in a few cases of male infertility, more multicentre, double-blind studies performed with the same criteria are necessarv for an increased understanding of the effects of various antioxidants on fertility,

关键词： antioxidants male infertility oxidative stress reactive oxygen species

A decade of WH02010:total sperm number temporal trend and role of lifestyle factors

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Asian Journal of Andrology 2023年第5期25卷 572-577页

作者： Francesco Cargnelutti Francesco Pallotti Tania Carlini Fabiana Faja Anna Rita Vestri Danilo Alunni Fegatelli Andrea Lenzi Francesco Lombardo Donatella Paoli Laboratory of Seminology-Sperm Bank"Loredana Gandini" Department of Experimental MedicineSapienza University of RomeViale del Pliclinico 155Roma 00161Italy Department of Public Health and Infectious Disease Sapienza University of RomeViale del Polclinico 155Roma 00161Italy

After a huge decline in sperm concentration between 1938 and 1991 was reported,many researchers investigated the possibility of a worsening of human sperm quality.Despite massive efforts,published evidence is still controversial.Similarly,the role of lifestyle factors on semen parameters is debated.We conducted a monocentric Italian study to evaluate the total sperm number trend over the last 10 years(from 2010 to 2019).Additionally,we evaluated the association between lifestyle factors and total sperm number in order to identify possible damaging factors.We performed a retrospective study analyzing subjects aged 18-55 years who had their semen analyzed between 2010 and 2019.A total of 3329 subjects were included:1655 subjects referred to our department(Department of Experimental Medicine,Sapienza University of Rome,Roma,Italy)for idiopathic infertility and 1674 subjects referred for preconceptional or andrological screening with no confirmed andrological diseases.Semen samples were examined according to World Health Organization(WHO)2010 criteria by two seminologists with the same training and the same equipment.For statistical evaluations,only total sperm number(×10^(6)per ejaculate)was taken into consideration.We detected no significant changes in mean total sperm number during the last decade,in either the entire population or the two subgroups(infertile group and control group).In a multivariate analysis total sperm number was significantly associated with the history of infertility,body mass index(BMI)and cigarette smoking.Our results suggest that infertile men are"vulnerable"subjects,particularly susceptible to several negative factors,many of which still remain unknown.Our study highlights the need for studies addressing men's lifestyle in order to find and reduce deleterious agents.

关键词： aging male infertility obesity smoking sperm decline

Negative association between trunk fat, insulin resistance and skeleton in obese women

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World Journal of Diabetes 2013年第2期4卷 31-39页

作者： Emanuela A Greco Davide Francomano Rachele Fornari Chiara Marocco Carla Lubrano Vincenza Papa Francesca Wannenes Luigi Di Luigi Lorenzo M Donini Andrea Lenzi Antonio Aversa Silvia Migliaccio Department of Experimental Medicine Section of Medical Pathophysiology Endocrinology and Nutrition University "Sapienza"of Rome Department of Experimental Medicine Section of Medical Pathophysiology Endocrinology and Nutrition University "Sapienza" of Rome Unit of Endocrinology Department of Health Sciences University "Foro Italico" of Rome

AIM: To evaluate the potential interference of trunk fat (TF) mass on metabolic and skeletal metabolism. METHODS: In this cross-sectional study, 340 obese women (mean age: 44.8 ± 14 years; body mass index: 36.0 ± 5.9 kg/m 2 ) were included. Patients were evaluated for serum vitamin D, osteocalcin (OSCA), inflammatory markers, lipids, glucose and insulin (homeostasis model assessment of insulin resistance, HOMA-IR) levels, and hormones profile. Moreover, all patients underwent measurements of bone mineral density (BMD;at lumbar and hip site) and body composition (lean mass, total and trunk fat mass) by dual-energy X-ray absorptiometry. RESULTS: Data showed that: (1) high TF mass was inversely correlated with low BMD both at lumbar (P < 0.001) and hip (P < 0.01) sites and with serum vitamin D (P < 0.0005), OSCA (P < 0.0001) and insulin-like growth factor-1 (IGF-1; P < 0.0001) levels; (2) a positive correlation was found between TF and HOMA-IR (P < 0.01), fibrinogen (P < 0.0001) and erythrocyte sedimentation rate (P < 0.0001); (3) vitamin D levels were directly correlated with IGF-1 (P < 0.0005), lumbar (P < 0.006) and hip (P < 0.01) BMD; and (4) inversely with HOMA-IR (P < 0.001) and fibrinogen (P < 0.0005). Multivariate analysis demonstrated that only vitamin D was independent of TF variable. CONCLUSION: In obese women, TF negatively correlates with BMD independently from vitamin D levels. Reduced IGF-1 and increased inflammatory markers might be some important determinants that account for this relationship.

关键词： Obesity Skeleton Vitamin D Osteocalcin Insulin resistance Trunk fat Inflammation

Sarcopenic Obesity: Correlation with Clinical, Functional, and Psychological Status in a Rehabilitation Setting

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Food and Nutrition Sciences 2014年第20期5卷 2020-2031页

作者： Lorenzo M. Donini Eleonora Poggiogalle Silvia Migliaccio Alessandro Pinto Carla Lubrano Andrea Lenzi Food Science and Human Nutrition Research Unit Medical Physiopatology Food Science and Endocrinology Section Department of Experimental Medicine Sapienza University of Rome Rome Italy Unit of Endocrinology Department of Movement Human and Health Sciences ForoItalico University of Rome Rome Italy

Obesity and sarcopenia combination, appropriately defined as sarcopenic obesity (SO), due to disproportionally reduced/low lean body mass compared to excess fat mass, may lead to disability. Aims: The aim of our study was to investigate the relationship among sarcopenic obesity, physical performance, disability, and quality of life in a rehabilitation setting. Methods: Participants were recruited among obese patients (BMI > 30 kg/m2) admitted to the rehabilitation facility at the Department of Experimental Medicine, Medical Physiopatology, Food Science and Endocrinology Section during a 1-year period. A multidimensional evaluation was performed through bioelectrical impedance analysis and anthropometry, handgrip strength test, Short Physical Performance Battery (SPPB), 6-minute walk test (6MWT) and blood chemistry parameters. Psychological status (SCL-90 questionnaire), quality of life, and comorbidity (Charlson comorbidity index score) were also evaluated. Obesity was diagnosed as increased fat mass by 35% in women and by 25% in men. Sarcopenia was defined if lean body mass (LBM) was <90% of the subject’s ideal LBM. Results: 79 patients (48 women and 31 men;mean age: 60.1 ± 11.5 years, and 58.6 ± 10.8 years, respectively) were enrolled. Results showed a high prevalence of SO (54.4%) in our samples of obese subjects. Sarcopenia was present not only among older obese adults but also among younger obese subjects, and was related to reduced functional performance, to inflammatory status and to worse psychological status and quality of life.

关键词： Sarcopenic Obesity Disability