International journal of andrology最新文献

{"title":"Do men with prostate abnormalities (prostatitis/benign prostatic hyperplasia/prostate cancer) develop immunity to spermatozoa or seminal plasma?","authors":"P. Hoover,&nbsp;R. K. Naz","doi":"10.1111/j.1365-2605.2011.01246.x","DOIUrl":"10.1111/j.1365-2605.2011.01246.x","url":null,"abstract":"<p>Prostate is an immunocompetent and not an immunoprivileged organ. It has an active immunologic armamentarium. There are three major prostate abnormalities namely, prostatitis, benign prostatic hyperplasia (BPH) and prostate cancer. In all these abnormalities, infection/inflammation has been implicated. As infection/inflammation of the male genital tract can also be involved in induction of antisperm antibodies (ASA), this study was conducted to examine if these prostate abnormalities lead to the formation of ASA. Sera were obtained from normal healthy men (<i>n </i>=<i> </i>20), men with chronic prostatitis (<i>n </i>=<i> </i>20), men with BPH (<i>n </i>=<i> </i>25), men with prostate cancer (<i>n </i>=<i> </i>25) and immunoinfertile men (<i>n </i>=<i> </i>10). The presence of antisperm antibodies against lithium diiodosalicylate (LIS)-solubilized human sperm extract (HSE), seminal plasma and synthetic peptides based upon sperm-specific antigens namely fertilization antigen (FA-1) and YLP₁₂, were analysed using the sperm immobilization technique (SIT), tray agglutination technique (TAT), enzyme-linked immunosorbent assay (ELISA) and indirect immunobead binding technique (IBT). All the sera from normal men and men with prostate abnormalities (chronic prostatitis/BPH/prostate cancer) were found to be negative in SIT and TAT. In ELISA, a few sera from men having prostate abnormalities (4–24%) showed a weak positive immunoreactivity (2–3 SD units) with some of the spermatozoa/seminal plasma antigens. Majority of the samples did not show any immunoreactivity (&lt;2 SD units) in ELISA. Even the samples that showed a weak positive immunoreactivity in ELISA did not bind to live human sperm in IBT, indicating lack of sperm binding antibodies in these sera. In all these assays, the sera from immunoinfertile men were positive. Our findings indicate that chronic prostatitis, BPH and prostate cancer do not induce antibodies to spermatozoa, sperm-specific antigens and seminal plasma components. Although prostate is an immunologically competent organ, and its abnormalities cause a rise in circulating prostate-specific antigen (PSA), it appears that there is no concomitant induction of immunity to spermatozoa/seminal components including sperm-specific fertility-related antigens, thus not causing ASA-induced immunoinfertlity. This is the first study to our knowledge reporting the absence of ASA in men with BPH and prostate cancer.</p>","PeriodicalId":13890,"journal":{"name":"International journal of andrology","volume":"35 4","pages":"608-615"},"PeriodicalIF":0.0,"publicationDate":"2012-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1365-2605.2011.01246.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30449231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scrotal asymmetry, varicocoele and the Riace Bronzes","authors":"B. Bonafini,&nbsp;P. Pozzilli","doi":"10.1111/j.1365-2605.2011.01181.x","DOIUrl":"10.1111/j.1365-2605.2011.01181.x","url":null,"abstract":"<p>In 1972, a pair of remarkably attractive Greek statues, later named Riace Bronzes, were found along the Mediterranean coast in the province of Reggio Calabria, Italy. We analyse the Riace Bronzes in the context of previous research on scrotal asymmetry in Greek statues. By examining their testis, one can define a more exact time of their dating by placing them beside previous observations of scrotal asymmetry, and possibly by taking a pathological condition, varicocoele, as an influencing factor in determining the appearance of the testis. In statue A of the Riace Bronzes, the left testicle is remarkably lower compared with the right one; it also appears as it looks when under physical examination varicocoele is suspected. Being located on the left testicle (as in 90% of cases) and by sight, we feel sufficiently confident to affirm that varicocoele might be diagnosed.</p>","PeriodicalId":13890,"journal":{"name":"International journal of andrology","volume":"35 2","pages":"181-182"},"PeriodicalIF":0.0,"publicationDate":"2012-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1365-2605.2011.01181.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30422141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone mineral density, body composition and bone turnover in patients with congenital hypogonadotropic hypogonadism","authors":"E.-M. Laitinen,&nbsp;M. Hero,&nbsp;K. Vaaralahti,&nbsp;J. Tommiska,&nbsp;T. Raivio","doi":"10.1111/j.1365-2605.2011.01237.x","DOIUrl":"10.1111/j.1365-2605.2011.01237.x","url":null,"abstract":"<p>Patients with congenital hypogonadotropic hypogonadism (HH) may have reduced peak bone mass in early adulthood, and increased risk for osteoporosis despite long-term hormonal replacement therapy (HRT). To investigate the relationship between HRT history and measures of bone health in patients with HH, we recruited 33 subjects (24 men, nine women; mean age 39.8 years, range: 24.0–69.1) with congenital HH (Kallmann syndrome or normosmic HH). They underwent clinical examination, were interviewed and medical charts were reviewed. Twenty-six subjects underwent dual-energy X-ray absorptiometry for evaluation of BMD of lumbar spine, hip, femoral neck and whole body; body composition and vertebral morphology were evaluated in 22 and 23 subjects, respectively. Circulating PINP, ICTP and sex hormone levels were measured. HRT history clearly associated to bone health: BMDs of lumbar spine, femoral neck, hip and whole body were lower in subjects (<i>n </i>=<i> </i>9) who had had long (≥5 years) treatment pauses or low dose testosterone (T) treatment as compared to subjects without such history (<i>n </i>=<i> </i>17; all <i>p</i>-values &lt; 0.05). In addition, fat mass and body mass index (BMI) were significantly higher in men with deficient treatment history (median fat mass: 37.5 vs. 23.1%, <i>p </i>=<i> </i>0.005; BMI: 32.6 vs. 25.2 kg/m², <i>p </i>&lt;<i> </i>0.05). Serum PINP correlated with ICTP (<i>r</i>_s<i> </i>=<i> </i>0.61; <i>p </i>&lt;<i> </i>0.005) in men, but these markers correlated neither with circulating T, nor with serum estradiol levels in women. In conclusion, patients with congenital HH require life-long follow-up to avoid inadequate HRT, long treatment pauses and further morbidity.</p>","PeriodicalId":13890,"journal":{"name":"International journal of andrology","volume":"35 4","pages":"534-540"},"PeriodicalIF":0.0,"publicationDate":"2012-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1365-2605.2011.01237.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30388360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of dihydrotestosterone exposure during or prior to the masculinization programming window on reproductive development in male and female rats","authors":"A. Dean,&nbsp;L. B. Smith,&nbsp;S. Macpherson,&nbsp;R. M. Sharpe","doi":"10.1111/j.1365-2605.2011.01236.x","DOIUrl":"10.1111/j.1365-2605.2011.01236.x","url":null,"abstract":"<p>Masculinization is programmed by androgen exposure during a masculinization programming window (MPW). Deficiency in MPW androgen action results in reduced size of all reproductive organs and anogenital distance (AGD) and reproductive disorders. Although timing of MPW closing has been defined, what determines ‘opening’ and ‘closing’ of the MPW remains unknown. To test whether initiation of testosterone production/action defines the opening of the window, we first demonstrated that androgen receptor mRNA and protein are expressed prior to the MPW, and then investigated whether masculinization could be advanced or enhanced by treating pregnant rats with either 1 or 10 mg/kg/day dihydrotestosterone (DHT) prior to (early window, EW; e11.5–e14.5) or during the MPW (e15.5–e18.5), and then evaluating offspring in foetal life (e18.5, e21.5), early puberty (day 25) or adulthood (∼day 75). DHT treatment did not affect pregnancy duration, birth, litter or pup size. DHT exposure in either time window did not advance foetal male development (Wolffian duct coiling) and had no effect on AGD, testis, penis and ventral prostate (VP) size at any age when measured; there was a tendency towards smaller penis size. In contrast, exposure of females to 10 mg DHT in either time window induced varying degrees of masculinization, including stabilization of the Wolffian duct and increased AGD (e21.5, Pnd25), VP formation, more male-like phallus structure, absence of nipples and vaginal opening and, in some adult females, gross fluid distension of the uterus (hydrometrocolpos); these effects were generally more pronounced after exposure in the MPW than in the EW. In conclusion, exposure of the male rat foetus to additional androgens prior to or during the MPW does not advance or enhance any measured parameter of reproductive development. Therefore, androgen availability plays no role in determining timing of the MPW. Susceptibility of the female reproductive system to androgens may precede the MPW.</p>","PeriodicalId":13890,"journal":{"name":"International journal of andrology","volume":"35 3","pages":"330-339"},"PeriodicalIF":0.0,"publicationDate":"2012-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1365-2605.2011.01236.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30388565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The endocrine disruptors dibutyl phthalate (DBP) and diethylstilbestrol (DES) influence Leydig cell regeneration following ethane dimethane sulphonate treatment of adult male rats","authors":"K. Heng,&nbsp;R. Anand-Ivell,&nbsp;K. Teerds,&nbsp;R. Ivell","doi":"10.1111/j.1365-2605.2011.01231.x","DOIUrl":"10.1111/j.1365-2605.2011.01231.x","url":null,"abstract":"<p>The manner by which endocrine-disrupting xenobiotics, such as phthalates, can induce changes in the development of the male reproductive system still remains largely unknown. Herein, we have explored the application of ethane dimethane sulphonate (EDS) to eliminate adult-type Leydig cells in the mature rat testis, leading to their regeneration from resident stem cells, as a novel system to investigate the effects of dibutyl phthalate (DBP) and diethylstilbestrol (DES) on adult-type Leydig cell differentiation. The advantage of this model is that one can study adult-type Leydig cell differentiation in vivo divorced from the concomitant endocrine development of puberty. In these preliminary studies, we show that both DBP and/or DES, given for 2 or 4 days following EDS application, indeed affect Leydig cell differentiation in the adult testis, largely by increasing early Leydig cell proliferation and possibly thereby delaying early differentiation. In particular, on day 27 post-EDS, a time-point when the differentiation trajectory appears to be most discriminating, we observe that both DBP and/or DES cause a fourfold increase in Leydig cell density, and a significant increase in the expression of the Leydig cell-specific marker transcripts INSL3, LH receptor, Cyp17a1 and Cyp 11a1. In conclusion, both DBP and DES are able to affect adult-type Leydig cells during their differentiation to cause a significant perturbation in their ultimate functional capacity.</p>","PeriodicalId":13890,"journal":{"name":"International journal of andrology","volume":"35 3","pages":"353-363"},"PeriodicalIF":0.0,"publicationDate":"2011-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1365-2605.2011.01231.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30309370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in sex hormone concentrations in US males: 1988–1991 to 1999–2004","authors":"S. J. Nyante,&nbsp;B. I. Graubard,&nbsp;Y. Li,&nbsp;G. M. McQuillan,&nbsp;E. A. Platz,&nbsp;S. Rohrmann,&nbsp;G. Bradwin,&nbsp;K. A. McGlynn","doi":"10.1111/j.1365-2605.2011.01230.x","DOIUrl":"10.1111/j.1365-2605.2011.01230.x","url":null,"abstract":"<p>Previous studies suggest that male testosterone concentrations have declined over time. To explore this in a large US population, we examined testosterone and free testosterone concentrations in National Health and Nutrition Examination Surveys (NHANES) from 1988–1991 and 1999–2004. We also examined sex hormone-binding globulin (SHBG), estradiol, and androstanediol glucuronide (3α-diol-G) over the same period. Non-Hispanic white, non-Hispanic black, and Mexican-American men from 1988–1991 and 1999–2004 NHANES surveys who were ≥20 years old and had serum from morning blood draws were included in this analysis (1988–1991: <i>N</i> = 1,413; 1999–2004: <i>N</i> = 902). Testosterone, estradiol and SHBG were measured by competitive electrochemiluminescence immunoassays and 3α-diol-G was measured by enzyme immunoassay. Free testosterone was calculated using testosterone and SHBG values. Adjusted mean hormone concentrations were estimated using linear regression, accounting for NHANES sampling weights and design, age, race/ethnicity, body mass index, waist circumference, alcohol use and smoking. Differences in adjusted mean concentrations (Δ) and two-sided <i>p</i>-values were calculated; <i>p</i> &lt; 0.05 was statistically significant. Overall, 3α-diol-G and estradiol declined between 1988–1991 and 1999–2004, but there was little change in testosterone, free testosterone, or SHBG (Δ: 3α-diol-G = −1.83 ng/mL, <i>p</i> &lt; 0.01; estradiol = −6.07 pg/mL, <i>p</i> &lt; 0.01; testosterone = −0.03 ng/mL, <i>p</i> = 0.75; free testosterone = −0.001 ng/mL, <i>p</i> = 0.67; SHBG = −1.17 nmol/L, <i>p</i> = 0.19). Stratification by age and race revealed that SHBG and 3α-diol-G declined among whites 20–44 years old (Δ: SHBG = −5.14 nmol/L, <i>p</i> &lt; 0.01; 3α-diol-G = −2.89 ng/mL, <i>p</i> &lt; 0.01) and free testosterone increased among blacks 20–44 years old (Δ: 0.014 ng/mL, <i>p</i> = 0.03). Estradiol declined among all ages of whites and Mexican-Americans. In conclusion, there was no evidence for testosterone decline between 1988–1991 and 1999–2004 in the US general population. Subgroup analyses suggest that SHBG and 3α-diol-G declined in young white men, estradiol declined in white and Mexican-American men, and free testosterone increased in young black men. These changes may be related to the increasing prevalence of reproductive disorders in young men.</p>","PeriodicalId":13890,"journal":{"name":"International journal of andrology","volume":"35 3","pages":"456-466"},"PeriodicalIF":0.0,"publicationDate":"2011-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1365-2605.2011.01230.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30308433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Foetal and post-natal exposure of sheep to sewage sludge chemicals disrupts sperm production in adulthood in a subset of animals","authors":"M. Bellingham,&nbsp;C. McKinnell,&nbsp;P. A. Fowler,&nbsp;M. R. Amezaga,&nbsp;Z. Zhang,&nbsp;S. M. Rhind,&nbsp;C. Cotinot,&nbsp;B. Mandon-Pepin,&nbsp;N. P. Evans,&nbsp;R. M. Sharpe","doi":"10.1111/j.1365-2605.2011.01234.x","DOIUrl":"10.1111/j.1365-2605.2011.01234.x","url":null,"abstract":"<p>Exposure to ubiquitous, environmental chemicals (ECs) has been hypothesized as a cause for declining male reproductive health. Understanding the long-term effects of EC exposure on reproductive health in humans requires animal models and exposure to ‘real life’, environmentally relevant, mixtures during development, a life stage of particular sensitivity to ECs. The aim of this study was to evaluate the effects of in utero and post-natal exposure to environmentally relevant levels of ECs, via sewage sludge application to pasture, on the adult male sheep testis. Hormones, liver concentrations of candidate ECs and Sertoli and germ cell numbers in testes of adult rams that were exposed to ECs in sewage sludge in utero, and until weaning via maternal exposure, and post-weaning via grazing pastures fertilized with sewage sludge, were quantified. Evaluated as a single group, exposure to sludge ECs was without significant effect on most parameters. However, a more detailed study revealed that 5 of 12 sludge-exposed rams exhibited major spermatogenic abnormalities. These consisted of major reductions in germ cell numbers per testis or per Sertoli cell and more Sertoli cell-only tubules, when compared with controls, which did not show any such changes. The sludge-related spermatogenic changes in the five affected animals were significantly different from controls (<i>p</i> &lt; 0.001); Sertoli cell number was unaffected. Hormone profiles and liver candidate EC concentrations were not measurably affected by exposure. We conclude that developmental exposure of male sheep to real-world mixtures of ECs can result in major reduction in germ cell numbers, indicative of impaired sperm production, in a proportion of exposed males. The individual-specific effects are presumed to reflect EC effects on a heterogeneous population in which some individuals may be more susceptible to adverse EC effects. Such effects of EC exposure in humans could have adverse consequences for sperm counts and fertility in some exposed males.</p>","PeriodicalId":13890,"journal":{"name":"International journal of andrology","volume":"35 3","pages":"317-329"},"PeriodicalIF":0.0,"publicationDate":"2011-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1365-2605.2011.01234.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30309084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semen variation in a population of fertile donors: evaluation in a French centre over a 34-year period","authors":"C. Splingart,&nbsp;C. Frapsauce,&nbsp;S. Veau,&nbsp;C. Barthélémy,&nbsp;D. Royère,&nbsp;F. Guérif","doi":"10.1111/j.1365-2605.2011.01229.x","DOIUrl":"10.1111/j.1365-2605.2011.01229.x","url":null,"abstract":"<p>Although it has been suspected that there is a decrease in semen quality over time, the results reported to date remain debatable because of methodological issues. The aim of the study reported here was to investigate the evolution of semen quality over time in a population of 1114 fertile candidates for sperm donation at CECOS, Tours, between 1976 and 2009. We investigated semen volume, sperm concentration, progressive motility, vitality, percentage of normal forms and multiple abnormalities index of the first ejaculate in this population. We did not find a decline in semen volume, whereas we observed a significant decrease in total sperm count (from 443.2 million in 1976 to 300.2 million in 2009), motility (from 64% in 1976 to 49% in 2009) and vitality (from 88% to 80%). Moreover, a significant decline in the percentage of normal forms was noted between 1976 and 1997 (from 67% to 26%) with a steady rise in the multiple abnormalities index between 1998 and 2009 (from 1.19 to 1.65). This study involving a population of fertile men from a restricted area revealed various degrees of decline in semen parameters over a period of 34 years. These findings will have to be compared with findings in other geographical areas.</p>","PeriodicalId":13890,"journal":{"name":"International journal of andrology","volume":"35 3","pages":"467-474"},"PeriodicalIF":0.0,"publicationDate":"2011-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1365-2605.2011.01229.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30309323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure of neonatal rats to anti-androgens induces penile mal-developments and infertility comparable to those induced by oestrogens","authors":"L. Simon,&nbsp;L. Avery,&nbsp;T. D. Braden,&nbsp;C. S. Williams,&nbsp;L. A. Okumu,&nbsp;J. W. Williams,&nbsp;H. O. Goyal","doi":"10.1111/j.1365-2605.2011.01232.x","DOIUrl":"10.1111/j.1365-2605.2011.01232.x","url":null,"abstract":"<p>We previously reported that oestrogen exposure in neonatal rats induced permanent infertility and malformed penis characterized by fat accumulation, which replaced most of the smooth muscle cells and cavernous spaces in the body of the penis, structures essential for erection. The objective of this study was to determine if reduced androgen production/action in the neonatal period, in the absence of exogenous oestrogen exposure, induces penile deformities similar to those caused by oestrogen. Male rats were treated from postnatal days 1–6 with GnRH antagonist antide (A, 10 mg/kg) or androgen receptor (AR) antagonist flutamide (F, 50 mg/kg) or F + A, with or without AR agonist dihydrotestosterone (DHT, 20 mg/kg). For comparison, pups received diethylstilbestrol (DES, 0.1 mg/kg), with or without DHT. Tissues were collected at ages 7 and 12 days and at adulthood. Flutamide alone decreased penile length and weight significantly (<i>p</i> &lt; 0.05), but it caused neither fat accumulation, nor affected fertility (80% vs. 87% in controls). Antide alone reduced penile length and weight significantly, and induced fat accumulation in 4/11 rats and infertility in 13/14 rats. Conversely, all 11 F + A-treated rats, similar to all nine DES-treated rats, had fat accumulation and loss of smooth muscle cells and cavernous spaces in the body of the penis and were infertile. In addition, reductions in penile length and weight were higher than in rats treated with F or A alone. DHT co-administration mitigated penile deformities in the DES group, but did not in the F + A group. Testicular testosterone was reduced by 70–95% at 7 or 12 days of age in all treated groups, except in the F group, which had threefold higher testosterone than controls. Collectively, data unequivocally show that reduced androgen production/action in the neonatal period, in the absence of oestrogen exposure, induces permanent infertility and malformed penis similar to that caused by oestrogen.</p>","PeriodicalId":13890,"journal":{"name":"International journal of andrology","volume":"35 3","pages":"364-376"},"PeriodicalIF":0.0,"publicationDate":"2011-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1365-2605.2011.01232.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30308996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mixed testicular atrophy related to atherosclerosis: first lessons from the ApoE−/−/ LDL receptor−/− double knockout mouse model","authors":"A. C. Langheinrich,&nbsp;A. Paradowska,&nbsp;R. Kilinski,&nbsp;M. Kampschulte,&nbsp;K. Steinfeld,&nbsp;B. Altinkilic,&nbsp;K. Steger,&nbsp;P. Stieger,&nbsp;M. Bergmann,&nbsp;W. Weidner","doi":"10.1111/j.1365-2605.2011.01228.x","DOIUrl":"10.1111/j.1365-2605.2011.01228.x","url":null,"abstract":"<p>Age-related testicular changes are associated with declining spermatogenesis and testosterone levels. A relationship to atherosclerosis has never been investigated systematically. The ApoE^−/−/LDL receptor^−/− double knockout mouse model, providing a remarkable homology to human atherosclerosis, is an ideal tool to investigate spermatogenetic alterations in this context. Testes (<i>n </i>= 10) from ApoE^−/−/LDL receptor^−/− double knockout mice at the age of 80 weeks were perfused <i>in vivo</i> with contrast agent, harvested and scanned with micro-CT at (4.9 μm³) voxel size. Testes (<i>n </i>= 8) of C57/BL mice at the same age served as controls. Testis volume (mm³) and total vascular volume fraction (mm³) were quantified using micro-CT. Serum testosterone levels were determined. Testicular histology and epididymal sections were analysed for tubular structure, spermatogenetic scores and sperm count. The expression of protamine 2 as a marker for elongated spermatids, inflammation markers (CD4, F4/80) and hypoxia inducible factor 1 alpha (HIF1 alpha) were investigated using immunohistochemistry. ApoE^−/−/LDL receptor^−/− double knockout mice exhibit diminished testis and vascular volume fraction with respect to that of controls (<i>p </i>&lt; 0.001). These findings were associated with a reduction of testosterone levels (<i>p </i>&lt; 0.001). Mixed atrophy was present in 41% of the seminiferous tubuli in ApoE^−/−/LDL receptor^−/− double knockout mice at the age of 80 weeks. Sperm counts from the epididymis demonstrated a significant decrease in ApoE^−/−/LDL receptor^−/− double knockout mice (<i>p </i>&lt; 0.001). In addition, sperm specific protamine 2 expression was decreased in testicular tissue and epididymis of ApoE^−/−/LDL receptor^−/− double knockout mice compared with that of control mice. Peritubular inflammatory infiltration and the expression of the hypoxia related marker was observed. Mixed testicular atrophy in ApoE^−/−/LDL receptor^−/− double knockout mice is linked to reduced testis volume, vascular volume fraction and low testosterone serum levels, suggesting a direct relation between atherosclerosis and disturbed spermatogenesis.</p>","PeriodicalId":13890,"journal":{"name":"International journal of andrology","volume":"35 4","pages":"562-571"},"PeriodicalIF":0.0,"publicationDate":"2011-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1365-2605.2011.01228.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30308979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}