Testicular Microcirculation Research Articles

Testicular ultrasonic microvascular density in assessing spermatogenesis and predicting successful sperm retrieval.

The relationship between microcirculatory disorders and testicular spermatogenesis is an area of ongoing interest among urologists. The objective of this prospective observational study was to investigate the correlation between testicular microcirculation and spermatogenesis, as well as the predictive value of ultrasonic microvascular density (UMVD) and ultrasonographic volume estimation (UVE) in successful sperm retrieval among men with non-obstructive azoospermia (NOA). Testicular UMVD derived from Angio PLUSTM Planwave Ultrasensitive Imaging (AP), UVE were obtained. Participants were divided into 4 groups (normozoospermia; asthenozoospermia, teratozoospermia, or asthenoteratozoospermia; oligozoospermia; NOA). The study included a total of 875 participants. No significant difference was found in UMVD-mean between different semen groups (P>0.05). A total of 108 participants with NOA underwent microdissection testicular sperm extraction (micro-TESE). Participants with successful sperm retrieval (40 cases) showed significant differences in testicular UMVD and UVE compared to those with negative retrieval (68 cases) (P<0.01). We generated receiver operating characteristic (ROC) curves for UMVD and testicular UVE to differentiate participants with successful sperm retrieval from those without. The area under the curve (AUC) was 0.760 [95% confidence interval (CI): 0.658-0.849, P<0.01] for UMVD and 0.716 (95% CI: 0.609-0.822, P<0.01) for testicular UVE, respectively. The optimal cutoff value was determined based on the maximum Youden index. When UMVD was set at 28.50/cm2, its sensitivity and specificity were calculated as 57.5% and 85.3%, respectively. For testicular UVE, a cutoff value of 8.94 mL resulted in a sensitivity of 60.0% and specificity of 82.4%. Combining UMVD with testicular UVE improved diagnostic performance (AUC: 0.856, 95% CI: 0.772-0.929, P<0.01) with a sensitivity of 79.4% and specificity of 77.5%. The present study demonstrates the utility of AP as a predictive tool for successful sperm retrieval prior to micro-TESE. Furthermore, the combination of testicular UMVD and UVE provides a highly valuable diagnostic approach for predicting micro-TESE success and can be routinely implemented before the procedure. A testicular UMVD exceeding 28.50/cm2 and a testicular UVE larger than 8.94 mL strongly indicate favorable outcomes in terms of sperm retrieval.

Inside Front Cover: Super‐resolution ultrasound localization microscopy for the non‐invasive imaging of human testicular microcirculation and its differential diagnosis role in male infertility (View 2/2024)

Inside Front Cover: Super‐resolution ultrasound localization microscopy for the non‐invasive imaging of human testicular microcirculation and its differential diagnosis role in male infertility (View 2/2024)

Super‐resolution ultrasound localization microscopy for the non‐invasive imaging of human testicular microcirculation and its differential diagnosis role in male infertility

AbstractTesticular microcirculation is closely related to spermatogenic function and seminiferous tubular function. The diagnosis and monitoring of testicular diseases can be associated with testicular microcirculation; however, there are currently no effective non‐invasive methods for super‐resolution imaging of testicular microcirculation. In this study, we introduced state‐of‐the‐art graph‐based tracking with the Kalman motion model algorithm to non‐invasively image human testicular microcirculation for the first time with a regular frame‐rate clinical ultrasound imaging system (37 Hz). Two distinct testicular vessels with an 81 µm separation were resolved in the testicular vasculature, surpassing all other imaging modalities. In a retrospective study, we performed contrast‐enhanced ultrasound examinations(CEUS) and ultrasound localization microscopy (ULM) processing on the included 76 infertile patients and 15 healthy controls from August 2021 to May 2023 and obtained super‐resolution images of testicular microcirculation with sub‐diffraction resolution. Through the results of one‐way analysis of variance tests and receiver operating characteristic analyses, we found that the ULM‐based parameters hold promise as clinical guidance for differentiating between non‐obstructive and obstructive male infertility. The mean vessel diameter achieved an area under the curve (AUC) of 0.920 (95% confidence interval [CI]: 0.847–0.994, p &lt; .001) with a cut‐off value of 170.9 µm in oligoasthenospermia, and an AUC of 0.952 (95% CI: 0.875–1.000, p &lt; .001) with a cut‐off value of 169.9 µm in azoospermia patients, respectively, addressing a significant clinical challenge.

Non-invasive ultrasound localization microscopy (ULM) in azoospermia: connecting testicular microcirculation to spermatogenic functions.

Rationale: Azoospermia is a significant reproductive challenge. Differentiating between non-obstructive azoospermia (NOA) and obstructive azoospermia (OA) is crucial as each type requires distinct management strategies. Testicular microcirculation plays a profound role in spermatogenic functions. However, current diagnostic methods are limited in their ability to effectively elucidate this crucial connection. Methods: We employed ultrasound localization microscopy (ULM) to visualize testicular microcirculation in NOA and OA patients and quantified the testicular hemodynamic parameters. Pearson correlation analysis was conducted to investigate the inner connection between parameters of testicular microcirculation and clinical spermatogenic functions. We conducted multiple logistic regression analysis to establish a new diagnostic model that integrates follicle-stimulating hormone (FSH) and mean vascular diameter to distinguish NOA from OA. Results: Our findings demonstrated significant differences in vascular parameters between NOA and OA, with NOA characterized by lower mean vascular diameter (p < 0.001), vessel density (p < 0.001), and fractal number (p < 0.001). Testicular volume showed a moderate positive correlation with mean vascular diameter (r = 0.419, p < 0.01) and vessel density (r = 0.415, p < 0.01); Mean vascular diameter exhibited negative correlations with both FSH (r = -0.214, p < 0.05) and age (r = -0.240, p < 0.05); FSH (r = -0.202, p < 0.05) and luteinizing hormone (LH) (r = -0.235, p < 0.05) were negatively correlated with mean blood flow velocity. The diagnostic model demonstrated an area under the curve (AUC) of 0.968. We also reported a method to map the vascular pressure distribution derived from the blood flow velocity generated by ULM. Conclusions: ULM provides a non-invasive and detailed assessment of testicular microvascular dynamics. The ULM-derived vascular parameters are able to connect testicular microcirculation to spermatogenic functions. The combination of FSH and mean vascular diameter enhances diagnostic precision and holds potential for distinguishing NOA from OA.

Testicular Microvascular Flow Is Altered in Klinefelter Syndrome and Predicts Circulating Testosterone.

Experimental studies on Klinefelter syndrome (KS) reported increased intratesticular testosterone (T) levels coexisting with reduced circulating levels. Abnormalities in testicular microcirculation have been claimed; however, no studies investigated in vivo testicular blood flow dynamics in humans with KS. To analyze the testicular microcirculation in KS by contrast-enhanced ultrasonography (CEUS) and correlate vascular parameters with endocrine function. Prospective study. University setting. Sixty-eight testicular scans, 34 testes from 19 T-naïve subjects with KS and 34 testes from age-matched eugonadal men (control) who underwent CEUS for incidental nonpalpable testicular lesions. CEUS kinetic parameters. CEUS revealed slower testicular perfusion kinetics in subjects with KS than in age-matched controls. Specifically, the wash-in time (P = 0.018), mean transit time (P = 0.035), time to peak (P < 0.001), and wash-out time (P = 0.004) were all prolonged. Faster testicular blood flow was associated with higher total T levels. Principal component analysis and multiple linear regression analyses confirmed the findings and supported a role for reduced venous blood flow as independent predictor of total T levels. Testicular venous blood flow is altered in KS and independently predicts T peripheral release.

Canine babesiosis \u2013 a disease rarely considered in the context of male infertility

BackgroundLittle is known about the impact of babesiosis on semen quality and fertility in dogs.Case presentationFour cases of infertility in male dogs after infection with Babesia canis are described. In all dogs sperm quality was low. Two dogs were castrated pharmacologically or surgically. In two dogs fertility was restored after supplementation with selenium and Vitamin E. As possible causes of spermatogenesis disorders due to the treatment of infection with Babesia canis with imidocarb, fever and disturbed testicular microcirculation are discussed.ConclusionsThese cases indicate that if males have fertility problems, question about babesiosis infection in the past should be a permanent point in the clinical interview.

Yangjing capsule attenuates cyclophosphamide-induced deficiency of testicular microcirculation in mice

Purpose: To explore the protective effects of Yangjing capsule (YC) on testicular microcirculation in a mouse model of deficiency of testicular microcirculation.&#x0D; Methods: Immunohistochemistry was applied to determine the effects of YC on microvascular density of mice. The protein level of CD34 and vascular endothelial growth factor A (VEGF A) was measured by western blot. The viability of Testicular cell line (TM4 cells) was examined by CCK-8 assay.&#x0D; Results: Histopathological changes demonstrated that CP-induced decrease of microvascular density of the mice was rescued by YC dose-dependently (p &lt; 0.5). Western blot data showed that the protein levels of CD34 and VEGF A in CP group were significantly decreased, but dose-dependently increased by YC, respectively, following co-administration of CP + YC, compared with those in CP group (p &lt; 0.5). The results from CCK-8 assay showed that the cell viability of TM4 cells increased with the amount of YC administered, and that high concentrations of YC (0.1 and 1 mg/mL) showed significant effects (p &lt; 0.5). Moreover, YC showed little effect on VEGF A mRNA and protein expression in TM4 cells.&#x0D; Conclusion: YC may be considered an alternative therapeutic agent for the management of testicular microcirculation disease. However, further studies are required to ascertain this.&#x0D; Keywords: Yangjing Capsule, Testicular microcirculation, Cyclophosphamide, Vascular endothelial growth factor A

Yangjing Capsule Can Improve the Function of the Testicular Angiogenesis through Activating VEGFA/eNOS Signaling Pathway.

Background The testicular microcirculation was an important aspect of testicular physiology and it offered a stable environment for the transport of nutrients and secretary products in the testis. Yangjing capsule (YC), a traditional Chinese compound herbal prescription, has been proved as an effective drug to ameliorate spermatogenesis, promote testosterone synthesis in vivo, and cure spermatogenesis in clinical practice. Objective This study was aimed at understanding the potential mechanisms of YC exerting angiogenic effects in the mouse spermatogenesis dysfunction model induced by cyclophosphamide (CP) and MLTC-1 cells. Materials and Methods Balb/c mice were randomly divided into five groups: control, CP, CP plus YC (630 mg/kg), CP plus YC (1260 mg/kg), and CP plus YC (2520 mg/kg). After 30 days, mice were sacrificed and the expressions of endothelial marker CD34+, angiogenic marker VEGFA, VEGFR1, VEGFR2, and eNOS in the testes of the mice were examined; moreover, Leydig cell line MLTC-1 cells were cultured and treated with different concentrations of YC extracts (YCE), and the expressions of VEGFA, VEGFR1, VEGFR2, and eNOS, as well as the secretion of NO, were evaluated. Results We observed that YC significantly increased the expressions of VEGFA, VEGFR1, VEGFR2, and eNOS in testes of CP-treated mice; moreover, YCE has led to increased expressions of VEGFA, VEGFR1, VEGFR2, and eNOS and secretion of NO in MLTC-1 in vitro. These data suggested that the YC might be an alternative treatment for the dysfunction of testicular microcirculation by promoting the angiogenesis in the testis.

Systemic arterial hypertension leads to decreased semen quality and alterations in the testicular microcirculation in rats

Arterial hypertension is a cardiovascular disease that leads to important systemic alterations and drastically impairs normal organ function over time. Hypertension affects around 700 million men of reproductive age and hypertensive men present increased risk for reproductive disorders, such as erectile dysfunction. However, the link between arterial hypertension and male reproductive disorders is associative at best. Moreover, many studies have reported associations between decreased male fertility and/or semen quality and alterations to general male health. In this study we aim to investigate the effect of systemic high blood pressure in sperm quality, sperm functional characteristics and testicular physiology in a rat model. Hypertensive rats presented altered testicular morphology – mainly vascular alterations and impaired testicular vasomotion. Hypertensive rats also presented decrease in sperm concentration, DNA integrity and increased percentages of sperm with dysfunctional mitochondria, intracellular superoxide anion activity and abnormal morphology. This study provides mechanistic insights by which arterial hypertension affects the testes, evidencing the testes as another target organ for hypertension as well as its impact on sperm quality.

Proteomic Signatures of Sperm Mitochondria in Varicocele: Clinical Use as Biomarkers of Varicocele Associated Infertility

Varicocele may disrupt testicular microcirculation and induce hypoxia-ischemia related degenerative changes in testicular cells and spermatozoa. Superoxide production at low oxygen concentration exacerbates oxidative stress in men with varicocele. Therefore, the current study was designed to study the role of mitochondrial redox regulation and its possible involvement in sperm dysfunction in varicocele associated infertility. We identified differentially expressed mitochondrial proteins in 50 infertile men with varicocele and in 10 fertile controls by secondary liquid chromatography-tandem mass spectroscopy data driven in silico analysis. Identified proteins were validated by Western blot and immunofluorescence. Seminal oxidation-reduction potential was measured. We identified 22 differentially expressed proteins related to mitochondrial structure (LETM1, EFHC, MIC60, PGAM5, ISOC2 and import TOM22) and function (NDFSU1, UQCRC2 and COX5B, and the core enzymes of carbohydrate and lipid metabolism). Cluster analysis and 3-dimensional principal component analysis revealed a significant difference between the groups. All proteins studied were under expressed in infertile men with varicocele. Liquid chromatography-tandem mass spectroscopy data were corroborated by Western blot and immunofluorescence. Impaired mitochondrial function was associated with decreased expression of the proteins (ATPase1A4, HSPA2, SPA17 and APOA1) responsible for proper sperm function, concomitant with elevated seminal oxidation-reduction potential in the semen of infertile patients with varicocele. Impaired mitochondrial structure and function in varicocele may lead to oxidative stress, reduced ATP synthesis and sperm dysfunction. Mitochondrial differentially expressed proteins should be explored for the development of biomarkers as a predictor of infertility in patients with varicocele. Antioxidant therapy targeting sperm mitochondria may help improve the fertility status of these patients.

Hyperglycemia induced testicular damage in type 2 diabetes mellitus rats exhibiting microcirculation impairments associated with vascular endothelial growth factor decreased via PI3K/Akt pathway.

As an endocrine disease, type 2 diabetes mellitus (T2DM) can cause testicular damage which induces male infertility. However, the underlying mechanism is still not clear. We prove that T2DM induced testicular microcirculation impairment involves the decrease of VEGF and these actions are regulated by PI3K/Akt pathway. In our study, rats were divided into three groups (n=8): control group, diabetes group and diabetes + VEGF group. Intraperitoneal injection of streptozotocin (STZ, 65mg/Kg, at 9th week) and daily high-fat diet were used to establish T2DM rat model. Serum glucose in diabetes group and diabetes + VEGF group obviously exceeded 13mmol/L after STZ injection. Immunohistochemical studies indicated that VEGF level in diabetes group significantly decreased. In diabetes group, testicular blood velocity and vascular area reduced evaluated by Doppler and FITC. Furthermore, atrophic testicular morphology and increasing apoptosis cells were evaluated by haematoxylin and eosin staining and TUNEL assay. In diabetes + VEGF group, the administration of VEGF (intraperitoneally, 10mg/kg) can significantly alleviated hyperglycemia-induced impairment of testes in above aspects. Finally, we used Western blot to analyze the mechanism of hyperglycemia-induced testicular VEGF decrease. The results indicated that hyperglycemia-induced VEGF decreased is regulated by PI3K/Akt pathway in Rats testicular sertoli cells (RTSCs). Together, we demonstrate that T2DM can reduce testicular VEGF expression, which results in testicular microcirculation impairment, and then induces testicular morphological disarrangement and functional disorder. These actions are triggered by PI3K/Akt pathway. Our findings provide solid evidence for VEGF becoming a therapeutic target in T2DM related male infertility.

Morphological and microcirculatory evaluation of the rat testis after detorsion with or without a capsular release with a tunica vaginalis flap.

Testicular torsion may lead to serious ischemia, and the viability depends on the duration of torsion and the effect of ischemia-reperfusion. Testicular decompression and tunica vaginalis flap application technique were introduced in 2008 by Kutikov et al. We aimed to examine the impact of this method on the testicular microcirculation and hemorheological parameters in a rat model. Six adult rats underwent bilateral scrotal exploration. Intravaginal torsion of the testis was created by 720° rotation on both sides for 2 h. After detorsion, the right testes underwent tunica albuginea incision and tunica vaginalis flap application. Testicular microcirculation was monitored and hematological parameters, erythrocyte deformability, and aggregation were determined. Measurements were performed before and after torsion, directly after detorsion, on the 1st–2nd and 8th postoperative day. After the last sampling, testicles were removed to determine their volume for histological examinations. The microcirculatory parameters demonstrated slight differences between testicles. Apical zone of the left (nondecompressed) testicles had elevated compared to the middle zone (P < 0.05). On the 2nd and 8th day, the microcirculation of the testes normalized but not equally. The erythrocyte aggregation and deformability decreased by the 8th day. Both testicles underwent atrophy and epithelial necrosis, but the volume of the decompressed ones was lower (1.07 ± 0.08 vs 1.25 ± 0.31). Histologically, there was no significant difference in epithelial damage score between decompressed and nondecompressed testes. In conclusion, 2-h ischemia led to alteration in testicular microcirculation, reduction in volume, changes in hemorheological parameters and serious epithelial necrosis both in decompressed and nondecompressed testicles without remarkable differences.

Testicular ischemia-reperfusion may alter micro-rheological parameters in laboratory rats

Ischemia-reperfusion-caused hemorheological alterations have been widely studied but the effect of testicular ischemia-reperfusion has not so far. In this study 14 Sprague-Dawley rats were involved. In the ischemia-reperfusion group under general anaesthesia the left testis was explored by opening the scrotum then the deferent duct and vasculature were clamped for 30 minutes. Testicular microcirculation was monitored by laser Doppler flowmetry. The right testis was untouched. In the control group: only anaesthesia was induced. Blood sampling occurred before and after ischemia, at the 60th minute of reperfusion and on the 1st postoperative day for determining hematological parameters (microcell-counter), erythrocyte deformability (slit-flow ektacytometer) and erythrocyte aggregation (light-transmission aggregometer). After the last blood sampling, testicles were removed for histological examination. Hematological parameter changes reflected inflammatory response. Erythrocyte deformability showed a worsening already at the 60th minute of reperfusion compared to base and control values. By the 1st postoperative day further decrease was observed. Erythrocyte aggregation significantly enhanced with great magnitude versus base and control values (p < 0.001). However, conventional histological examinations did not show marked testicular injury. The experienced changes can attract attention to the testicular ischemia-reperfusion causing significant effects on hemorheological parameters, which can lead to further harmful microcirculatory consequences.

Does varicocele ligation affect inrtatesticular resistive indices?

The Resistive Index (RI), calculated from the spectral waveform during the scrotal ultrasound (US) examination, is an indicator of the integrity of testicular microcirculation. Prior investigations have shown correlations between elevated RI and impaired spermatogenesis. This study characterizes changes in RI after varicocele ligation (VL).

Testicular ultrasound as a non-invasive indicator of testicular function

The Resistive Index (Ri) calculated from the spectral waveform during the scrotal ultrasound examination is an indicator of the integrity of the testicular microcirculation. This study attempts to determine the threshold Ri value for normal spermatogenesis.

Orthogonal Polarization Spectral Imaging: A Novel Tool for Examination of Microcirculatory Changes in the Testis

Testicular torsion is a surgical emergency in urologic practice. Many models have demonstrated the relationship between the degree and duration of the torsion and the subsequent damages of the testis, but there are as yet no suitable methods for visualization of the testicular microcirculation in this condition. We aimed to use orthogonal polarization spectral (OPS) imaging to observe the microcirculatory changes in the testis after ischemia-reperfusion (I/R) challenge, and to compare this technique with that of fluorescence intravital video microscopy (IVM). Twelve rats subjected to 60-minute ischemia following 720° testicular torsion were divided into two groups for IVM or OPS imaging examinations of the microcirculatory network of the testis at 60, 120, 180, and 240 minutes after reestablishment of perfusion. Significant microcirculatory failure was demonstrated after I/R in both groups. The absolute values of the microcirculatory parameters recorded with the OPS and IVM imaging methods did not differ statistically. The microcirculatory disturbances are present during the later phases of testicular torsion. OPS imaging technique represents an accurate noninvasive method to detect physiologic and pathophysiologic changes in the microcirculation of the testis.

2200 RESISTIVE INDEX DOES NOT VARY WITH LOCATION IN THE TESTIS

You have accessJournal of UrologyImaging/Radiology: Uroradiology II1 Apr 20122200 RESISTIVE INDEX DOES NOT VARY WITH LOCATION IN THE TESTIS Joel Hillelsohn, Mahyar Kashan, and Bruce Gilbert Joel HillelsohnJoel Hillelsohn Lake Success, NY More articles by this author , Mahyar KashanMahyar Kashan Lake Success, NY More articles by this author , and Bruce GilbertBruce Gilbert Lake Success, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2374AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Elevations in Resistive Index (Ri) is a non-invasive indicator of impaired testicular microcirculation, dyspermia and hypothalamic-pituitary-gonadal axis abnormalities. However, whether measurement varies with location in the testis has not been elucidated. This study answers this question by measuring the Ri of intratesticular arteries from the upper, middle and lower testis. METHODS The spectral Doppler evaluation was performed in 31 patients (59 testes) presenting with infertility or testicular pain and palpably normal testes. Our standard protocol included spectral Doppler interrogation of a single centripetal artery or recurrent rami from the upper, middle and lower portions of each testis. A BK medical Flex focus ultrasound with an 18 mHz linear array transducer was used by a single sonographer for all measurements. The groups were compared using t tests and ANOVA tests as appropriate. RESULTS Ri measured in the upper or lower testis did not significantly differ from mid testes. An ANOVA between the three groups also showed no significant difference (Right p= 0.52, Left p= 0.72). In addition, the average RI of both testes was not significantly different (p=0.82). These results are outlined in Table #1 and #2. Table #1. Ri Parameters vs Mid Testes Ri RI Mean ± SD p value vs mid testes Right Upper Testes 0.62±0.11 0.46 Right Mid Testes 0.59±0.13 1 Right Lower Testes 0.59±0.15 0.98 Left Upper Testes 0.62±0.15 0.35 Left Mid Testes 0.59±0.13 1 Left Lower Testes 0.61±0.15 0.48 Table #2. Average Ri Right Testes vs Ri Left Testes Right Testes Left Testes p= Varicocele Mean ± SD 5.4±1.3 5.4±1.7 0.96 Testes Volume 11.6±4.7 11.0±4.8 0.62 RI Mean ± SD 0.60±0.13 0.61±0.14 0.82 CONCLUSIONS Spectral Doppler results are equal whether taken from arteries in the upper, mid or lower testis. Ri does not vary with location in the testis. A single Ri measured anywhere in the testis is a valid indicator of testicular microcirculation. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e887 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joel Hillelsohn Lake Success, NY More articles by this author Mahyar Kashan Lake Success, NY More articles by this author Bruce Gilbert Lake Success, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Azoospermia and maturation arrest: malfunction of valves in erect poster of humans leads to hypoxia in sperm production site

Maturation arrest (MA) of spermatogenesis is diagnosed on histology as interruption of spermatogenesis before the final stage without impairment of Sertoli or Leydig cells. It is considered a condition of irreversible or absolute infertility. Varicocele, which represents impairment in the testicular venous drainage system, has been shown to be a bilateral disease. Malfunction of the valves increase the hydrostatic pressure in the testicular venous system that exceeds the pressure in the arterial system leading to hypoxia in the testicular microcirculation and in the seminiferous tubules, the sperm production site. Sperm production deteriorates, and ultimately progresses to azoospermia. Our prediction was that MA, if genetic factors are excluded, is the final stage of long standing hypoxia. This would indicate that MA is not always an independent disease entity, but may represent progressive process of deterioration of the testicular parenchyma beyond azoospermia. By histology and electron microscopy, our prediction confirmed, at least partially, that MA is associated with degenerative ischaemic changes in the seminiferous tubules. Adequate treatment of bilateral varicocele by microsurgery or super-selective sclerotherapy of the internal spermatic veins including associated network of venous bypasses, vertically oriented, may resume the flow of oxygenated blood. If irreversible damages did not occur and ischaemia is not too long standing, limited sperm production may be restored, at least partially.

Azoospermia and Sertoli-cell-only syndrome: hypoxia in the sperm production site due to impairment in venous drainage of male reproductive system

Sertoli-cell-only (SCO) syndrome, or germ cell aplasia, is diagnosed on testicular biopsy when germ cells are seen to be absent without histological impairment of Sertoli or Leydig cells. It is considered a situation of irreversible infertility. Recent studies have shown that varicocele, a bilateral disease, causes hypoxia in the testicular microcirculation. Destruction of one-way valves in the internal spermatic veins (ISV) elevates hydrostatic pressure in the testicular venules, exceeding the pressure in the arteriolar system. The positive pressure gradient between arterial and venous system is reversed, causing hypoxia in the sperm production site. Sperm production deteriorates gradually, progressing to azoospermia. Our prediction was that, if genetic problems are excluded, SCO may be the final stage of longstanding hypoxia which deteriorates sperm production in a progressive process over time. This would indicate that SCO is not always an independent disease entity, but may represent deterioration of the testicular parenchyma beyond azoospermia. Our prediction is confirmed by histology of the seminiferous tubules demonstrating that SCO is associated with extensive degenerative ischaemic changes and destruction of the normal architecture of the sperm production site. Adequate treatment of bilateral varicocele by microsurgery or by selective sclerotherapy of the ISV resumes, at least partially, the flow of oxygenated blood to the sperm production site and restored sperm production in 4 out of 10 patients. Based on our findings the following statements can be made: (i) SCO may be related in part of the cases to persistent, longstanding testicular parenchymal hypoxia; (ii) germ cells may still exist in other areas of the testicular parenchyma; and (iii) if genetic problems are excluded, adequate correction of the hypoxia may restore very limited sperm production in some patients.

Regulation of Neuropeptide Y Y1 Receptors by Testosterone in Vascular Smooth Muscle Cells in Rat Testis

It is well established that testosterone and neuropeptide Y (NPY), via its Y1 receptor (Y1R), are involved in the central control of the gonadotrope axis in male rats. Here we examined if a similar interaction also occurs in the male peripheral reproductive target organ, the testes. Expression of the Y1R transcript and protein and changes in testicular microcirculation were studied in normal rats and 12 days following hypophysectomy with and without testosterone substitution (1 or 25 mg s.c.). In situ hybridization and immunohistochemistry showed strong expression of, respectively, Y1R messenger RNA (Y1R mRNA) and Y1R-like immunoreactivity (Y1R-LI) in vascular smooth muscles in the testes of control and hypophysectomized rats treated with testosterone, but was not seen without testosterone substitution. In parallel, control animals and hypophysectomized, testosterone-supplemented rats showed a strong (approximately 40%) decrease in testicular blood flow following intratesticular (i.t.) injection of the Y1-R agonists, [Leu³¹, Pro³⁴]NPY, [D-Arg²⁵]NPY or NPY, an effect which was completely blocked by prior intravenous administration of the Y1R antagonist, BIBP3226. No significant change in testicular blood flow following i.t. injection of NPY was seen in hypophysectomized rats without testosterone substitution. These findings suggest that the high levels of Y1R mRNA and Y1R-LI in the testes reflect expression of functional Y1Rs mediating vasoconstriction, and that testosterone regulates expression of functional Y1Rs.