Testicular Hypoxia Research Articles

The impact of N-acetylcysteine on hypoxia-induced testicular apoptosis in male rats: TUNEL and IHC findings

The present study aimed to evaluate the impact of N-acetylcysteine (NAC) on testicular hypoxia caused by varicocele, focusing specifically on the regulation of genes related to apoptosis and oxidative stress in the testes of mature Wistar rats.Thirty-two rats were divided into four groups: Control (Sham), hypoxia, testicular hypoxia treated with NAC (Hypoxia + NAC), and healthy animals treated with NAC. After the 8-week treatment period, testicular histopathology and the levels of oxidative stress markers—superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA)—in serum were examined. The expression of Bax and Bcl-2 mRNA was analyzed using immunocytochemistry and RT-qPCR assays, while the apoptosis rate was determined using the TUNEL method.Histopathological evaluations showed that parameters such as Johnsen's score, epithelium width, and seminiferous tubule diameter indicated significant improvement in the Hypoxia + NAC group compared to the Hypoxia group. NAC administration resulted in elevated serum levels of GPx and SOD, accompanied by a reduction in MDA levels (p < 0.003). Furthermore, the study revealed that NAC decreased Bax expression and enhanced Bcl-2 gene and protein expression compared to the varicocele group (p < 0.05). Additionally, NAC administration significantly decreased the rate of apoptosis in germ cells (p < 0.05).These findings suggest that NAC administration can mitigate testicular damage induced by hypoxia from varicocele in rats, primarily due to its antioxidant properties.

Adolescent exposure to organophosphate insecticide malathion induces spermatogenesis dysfunction in mice by activating the HIF-1/MAPK/PI3K pathway

Chemical-caused reproductive dysfunction has emerged as a global public health concern. This study investigated the adverse effects of the organophosphorus pesticide malathion on reproductive function in adolescent male mice at environmentally relevant concentrations. The results indicated that eight-week malathion exposure reduced testis weight, caused sex and thyroid hormone disorders, and induced testicular spermatogenic epithelium damage and oxidative stress. Testicular RNA sequencing indicated that malathion significantly affected testicular energy metabolism, hypoxia-inducible factor 1 (HIF-1) signaling, and steroid hormone biosynthesis pathways. Malathion significantly increased the gene and protein expression of HIF-1α by upregulating key genes in the mitogen-activated protein kinase (MAPK) pathway (Map2k2, Mapk3, and Eif4e2) and the phosphatidylinositol 3-kinase (PI3K) pathway (Pik3r2 and Akt1). Furthermore, malathion downregulated HIF-1α degradation-regulating genes while upregulating anaerobic metabolism and inflammation-related genes, thereby inhibiting normoxia and promoting hypoxia processes. Testicular hypoxia subsequently induced steroid hormone biosynthesis disorders and spermatogenesis dysfunction. Molecular docking verified that malathion interfered with HIF-1α and steroid hormone synthases (CYP11A1, CYP17A1 and CYP19A1) by forming hydrogen bonds and hydrophobic interactions with these proteins. This study presents the first evidence that malathion triggers spermatogenesis dysfunction in mice through activating the HIF-1/MAPK/PI3K pathway, providing a comprehensive understanding of the reproductive toxicity risks associated with organophosphorus pesticides.

Investigating the Therapeutic Potential of Clove Extract in Mitigating Testicular Injury Associated With Testicular Hypoxia in Male Rats

Investigating the Therapeutic Potential of Clove Extract in Mitigating Testicular Injury Associated With Testicular Hypoxia in Male Rats

The Management of Clinical Varicocele: Robotic Surgery Approach.

Varicocele is a pathologic dilation of the testicular veins within the spermatic cord. Varicocele is considered the most common problem in reproductive medicine practice. It is identified in 15% of healthy men and up to 35% of men with primary infertility. The exact pathophysiology of varicoceles is not very well understood, and several theories have been proposed to explain it. Varicocele can impair sperm quality and fertility via various mechanisms: reflux of adrenal metabolites, increased testicular hypoxia, oxidative stress, and increased testicular temperature have been proposed. Several studies have reported the significant benefits on semen parameters with the surgical treatment of varicocele: reducing oxidatively induced sperm DNA damage and potentially improving fertility. Varicocele repair should be offered as a part of treatment option for male partners of infertile couples presenting with palpable varicoceles. Nowadays, there are several surgical approaches available for the treatment of varicocele, such as the retroperitoneal approach, inguinal approach, and the subinguinal approach. The subinguinal microscopic approach offers the best outcomes, such as shorter hospital stays, preservation of the testicular arteries and lymphatics, least number of postoperative complications, recurrence, and a higher number of pregnancies. Currently robotic-assisted laparoscopic surgery is widely adopted in urology and surgeons began to explore the potential applications of the robotic platform to male infertility microsurgical operations. Robotic approach offers many advantages: elimination of tremor, retraction with third arm, high quality, 3-dimensional visualization and surgeon ergonomics, all contributing to the precision of surgery.

Effect of Varicocelectomy on Gonadal Function among Patients Reporting with Sexual Dysfunction in Ghana

Background: Long-standing varicocele is often associated with testicular hypoxia and that might worsen Leydig cell function, a significant risk factor for hypogonadism. This may affect both the secretory and endocrine functions of the testis. This study aims to determine the effect of microsurgical sub-inguinal varicocelectomy on gonadal function among men reporting sexual dysfunction in Ghana. Methods: This was an intervention study conducted at the Tamale Teaching Hospital from September 2017 to August 2021. A total of 103 participants were randomized into two groups; the surgery group (n = 52) and the observed group (n = 51). Venous blood samples were collected at baseline, varicocelectomy was performed for the surgery group, and no intervention was given to the other. Blood samples were subsequently collected at 12-, 24-, 36-, and 48-month intervals for assay of serum total testosterone, FSH, and LH. The data were analyzed in GraphPad Prism (v8.0) at an alpha value of 0.05. Results: All the participants had varicocele and were aged between 55.0 to 69.0 years old. At the baseline of the study, all participants presented with sexual dysfunction but a significant improvement (p < 0.001) in the GRISS score, and the subscale was observed 12 months after the surgery. The mean ± SD serum total testosterone (p = 0.6078), FSH (p = 0.6522) and LH (p = 0.2281) between the groups at baseline did not vary but those in surgery group had improved values at 12-, 24-, 36- and 48-month post-surgery (p-trend < 0.0001). The surgery group had an overall percent increase in serum total testosterone (76.3%, 194.0%, 221.0%, and 231.9%) over 12-, 24-, 36- and 48-month and significant percent reduction in both FSH (-14.7%, -29.9%, -33.8% and -40.8%) and LH (-21.8%, -31.0%, -32.4%, and -36.4%) respectively. These gonadotropins observed annual percentages spike within the first and second year but changes were marginal from the third year onwards in the surgery group. Conclusions: Microsurgical sub-inguinal varicocelectomy improved gonadal function among varicocele patients reporting sexual dysfunction. It is recommended to use this choice for similar patients; however, these findings should be verified by a multi-institutional study to provide more evidence for this choice.

Short-term testicular warming under anesthesia causes similar increases in testicular blood flow in Bos taurus versus Bos indicus bulls, but no apparent hypoxia

Bull testes must be 4–5 °C below body temperature, with testicular warming more likely to cause poor-quality sperm in Bos taurus (European/British) versus Bos indicus (Indian/zebu) bulls. Despite a long-standing dogma that testicular hyperthermia causes hypoxia, we reported that increasing testicular temperature in bulls and rams enhanced testicular blood flow and O2 delivery/uptake, without hypoxia. Our objective was to determine effects of short-term testicular hyperthermia on testicular blood flow, O2 delivery and uptake and evidence of testicular hypoxia in pubertal Angus (B. taurus) and Nelore (B. indicus) bulls (nine per breed) under isoflurane anesthesia. As testes were warmed from 34 to 40 °C, there were increases (P < 0.0001, but no breed effects) in testicular blood flow (mean ± SEM, 9.59 ± 0.10 vs 17.67 ± 0.29 mL/min/100 g, respectively), O2 delivery (1.79 ± 0.06 vs 3.44 ± 0.11 mL O2/min/100 g) and O2 consumption (0.69 ± 0.07 vs 1.25 ± 0.54 mL O2/min/100 g), but no indications of testicular hypoxia. Hypotheses that: 1) both breeds increase testicular blood flow in response to testicular warming; and 2) neither breed has testicular hypoxia, were supported; however, the hypothesis that the relative increase in blood flow is greater in Angus versus Nelore was not supported. Although these were short-term increases in testicular temperature in anesthetized bulls, results did not support the long-standing dogma that increased testicular temperature does not increase testicular blood flow and an ensuing hypoxia is responsible for decreases in motile, morphologically normal and fertile sperm.

STRUCTURAL AND FUNCTIONAL CHANGES IN THE PROSTATE GLAND OF MEN OF OLDER AGE AT SUFFERING INGUINAL HERNIA

The research of structural and functional parameters of the prostate gland and the state of hemodynamics in it in case of testicular diseases are important for andrology, urology and gerontology, as even insignificant deviations of these parameters has negatively affect on the reproductive function and performance of male. Despite the considerable number of publications that relating to the prostate gland, their analysis shows that the structural and functional features of the blood vessels and tissue elements of this organ, in the conditions of inguinal hernia, is remained beyond the attention of researchers. However, the contents of a hernial sac in these conditions leads to chronic testicular hypoxia because of the contents of the hernial sac exerts the constant or periodic pressure on the testicular blood vessels, in particular on the wide and thin-walled testicular veins. Venous stagnation in the testicle violates thermoregulation, which is an important factor for the normal course of spermatogenesis and production of testosterone in interstitial endocrinocytes, and the prostate gland is the target for this hormone. Increase the concentration of testosterone in the blood leads to atrophy of the secretory epithelium of the lobules prostate gland and the development of connective tissue in it. Ultrasound and color ultrasound transrectal angiography of the prostate gland has been conducted in men of mature age (first period) with the inguinal hernia lasting of 3-5 years and has been showed a significant increase in peak blood flow (6,34±0,52) cm/sec and up to (2,42±0,31) cm/sec of diastolic blood flow compared to (19,32±3,28) cm/sec and (5,90±0,28) cm/sec on average in control group of male. These hemodynamic disorders were accompanied by an increase of up to (26,5 ± 1,7) cm3 of volume and up to (27,8 ± 1,6) g of mass of the prostate gland, which is markedly larger in comparison with the control. Such changes in parameters are due to the growth of connective tissue elements with a decrease of glandular parenchyma, the ratio between which is 56% versus 46%.

Increased testicular blood flow maintains oxygen delivery and avoids testicular hypoxia in response to reduced oxygen content in inspired air

Despite a long-standing assertion that mammalian testes operate near hypoxia and increased testicular temperature causes frank hypoxia, we have preliminary evidence that changes are due to hyperthermia per se. The objective was to determine how variations in inspired oxygen concentration affected testicular blood flow, oxygen delivery and extraction, testicular temperature and lactate production. Eight rams were maintained under general anesthesia, with successive decreases in oxygen concentration in inspired air (100, 21 and 13%, respectively). As oxygen concentration decreased from 100 to 13%, there were increases in testicular blood flow (9.6 ± 1.7 vs 12.9 ± 1.9 ml/min/100 g of testis, P < 0.05; mean ± SEM) and conductance (normalized flow; 0.46 ± 0.07 to 1.28 ± 0.19 ml/min/mm Hg/100 g testis (P < 0.05). Increased testicular blood flow maintained oxygen delivery and increased testicular temperature by ~1 °C; this increase was correlated to increased testicular blood flow (r = 0.35, P < 0.0001). Furthermore, oxygen utilization increased concomitantly and there were no significant differences among oxygen concentrations in blood pH, HCO3− or base excess, and no effects of venous-arterial differences in lactate production. In conclusion, under acute hypoxic conditions, testes maintained oxygen delivery and uptake by increasing blood flow and oxygen extraction, with no evidence of anaerobic metabolism. However, additional studies are needed to determine longer-term responses and potential evidence of anaerobic metabolism at the molecular level.

Hyperthermia and not hypoxia may reduce sperm motility and morphology following testicular hyperthermia

The mammalian testis typically operates on the brink of hypoxia; the long-standing dogma is that increased testicular temperature increases metabolism, but blood flow is unaffected and the resulting hypoxia reduces sperm motility and morphology. In rats and mice, oxygen (O&lt;sub&gt;2&lt;/sub&gt;) content of inspired air affected O&lt;sub&gt;2&lt;/sub&gt; content of testes, enabling the latter to range from approximately 50 to more than 200% of physiologic concentrations. A ram model was used to test the hypotheses that hypoxia would disrupt sperm motility and morphology and that hyperoxia would prevent hyperthermia-induced reductions in sperm motility and morphology. Eighteen Canadian Arcott rams (approximately 10 months old) were used in a 2 × 3 factorial, with factors being scrotal insulation (insulated or not insulated) and O&lt;sub&gt;2 &lt;/sub&gt;concentrations in inspired air (14, 21 or 85%). Six rams, three with and three without scrotal insulation, were placed in each of three enclosed areas for 30 h to expose them to their respective oxygen concentrations, with scrotal insulation removed at the end of the exposure. Semen was collected by electro-ejaculation twice before insulation, bi-weekly for four weeks starting one week after exposures, and then once weekly for two weeks. There were effects of insulation, time and an insulation × time interaction for motile sperm and sperm that had normal morphology or head or midpiece defects (P &amp;lt; 0.01 for each). Sperm motility and morphology exhibited alterations between approximately two and five weeks after insulation, with mean progressively motile and morphologically normal sperm decreasing from approximately 55 to 35% and from 80 to 30%, respectively, and with head and midpiece defects increasing from approximately 3 to 50% and from 10 to 20% (P &amp;lt; 0.05 for each). The hypotheses that hypoxia would disrupt sperm quality and production, whereas hyperoxia would prevent hyperthermia-induced reductions in sperm quality and production, were not supported. This is apparently the first report that heat-stress induced damage to sperm was due to increased temperature per se and not testicular hypoxia, calling into question a long-standing paradigm.

The hypoxic testicle: physiology and pathophysiology.

Mammalian spermatogenesis is a complex biological process occurring in the seminiferous tubules in the testis. This process represents a delicate balance between cell proliferation, differentiation, and apoptosis. In most mammals, the testicles are kept in the scrotum 2 to 7°C below body core temperature, and the spermatogenic process proceeds with a blood and oxygen supply that is fairly independent of changes in other vascular beds in the body. Despite this apparently well-controlled local environment, pathologies such as varicocele or testicular torsion and environmental exposure to low oxygen (hypoxia) can result in changes in blood flow, nutrients, and oxygen supply along with an increased local temperature that may induce adverse effects on Leydig cell function and spermatogenesis. These conditions may lead to male subfertility or infertility. Our literature analyses and our own results suggest that conditions such as germ cell apoptosis and DNA damage are common features in hypoxia and varicocele and testicular torsion. Furthermore, oxidative damage seems to be present in these conditions during the initiation stages of germ cell damage and apoptosis. Other mechanisms like membrane-bound metalloproteinases and phospholipase A2 activation could also be part of the pathophysiological consequences of testicular hypoxia.

Hypoxia‐Induced Apoptosis in the Bilateral Testes of Rats With Left‐Sided Varicocele: A New Way to Think About the Varicocele

Although the varicocele has been studied for many years, its pathophysiology remains unclear. In this study, we investigated the expression of the alpha subunit of hypoxia-inducible factor 1 (HIF-1 alpha) and determined the apoptosis index (AI) in the testes of rats with varicoceles to study the mechanism by which varicoceles induce infertility. A total of 45 Wistar rats were divided into 3 groups: control group, sham surgery group, and experimental group. Forty-nine days after the initial partial ligation of the left renal vein, all of the rats underwent orchiectomy. HIF-1 alpha expression in each testis was analyzed using immunohistochemical methods and enzyme-linked immunosorbent assay. The degree of apoptosis within each testicle was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling. HIF-1 alpha immunoreactivity in the testes of the experimental group was significantly higher than that in those of the control group (P < .05) or the sham group (P < .05). The AI of the germ cells of rats in the experimental group was significantly higher than that in germ cells of rats in the sham group (P < .001) or the control group (P < .001). Additionally, there was a significant positive correlation observed between the AI of germ cells and relative intensity of HIF-1 alpha in the left testis (r = .631; P = .028) and right testis (r = .707; P = .01) of rats in the experimental group. The results of this study showed that a left-sided varicocele could cause bilateral testicular hypoxia and increased germ cell apoptosis, both of which play an important role in testicular dysfunction. Furthermore, HIF-1 alpha is a useful factor that can be used to predict the degree of germ cell apoptosis in rat testes.

Lactate and pyruvate levels in the testicular vein of subfertile males with varicocele as a test for the theory of underlying hypoxia.

To test for the theory of testicular hypoxia in subfertile males with varicocele, the testicular mean blood level of lactate and pyruvate was compared with that of a control group. Statistical analysis of data showed a lower mean of lactate and of pyruvate in the testicular vein of varicocele patients. It is concluded that in varicocele there is no accumulation of lactic acid, thus excluding testicular hypoxia. Since lactate and pyruvate mean concentrations in testicular vein were correlated, it is suggested that in cases of varicocele there is defective glycolysis preceding the stage of pyruvate formation.

Semen analysis in sickle cell disease.

Male reproductive function has been poorly studied in sickle cell disease. Low sperm count, impaired motility of spermatozoa and spermatogenic arrest during testicular biopsies have been described in this situation. In the present series of patients, the main seminal changes found were reduced forward progression of spermatozoa and high incidence of the stress pattern during morphologic analysis. Since these findings closely resemble that seminal picture observed during varicocele, testicular hypoxia has been expected by the authors to be a possible stressing factor both common to falcemic and varicocele patients.

Parenchymal Echo Texture Predicts Testicular Salvage After Torsion: Potential Impact on the Need for Emergent Exploration

In the setting of signs and symptoms of testicular torsion the absence of diastolic flow and/or color flow on Doppler ultrasound has traditionally prompted emergent scrotal exploration. This practice emanates largely from the difficulty on ultrasound of distinguishing salvageable torsed testes from those that are not salvageable. We identified ultrasound findings predictive of testicular viability or the lack thereof. We retrospectively reviewed the charts of all boys who underwent scrotal exploration for signs and symptoms of torsion during a 4-year period. In those who underwent preoperative Doppler ultrasound of the scrotum ultrasound findings were reviewed, as were the operative dictations. In patients who underwent orchiectomy the pathology reports were also reviewed. In patients in whom the torsed testis appeared viable and who underwent orchiopexy followup data were reviewed when available. Emergency room charts were also reviewed to ascertain, when documented, the duration of pain before presentation to the emergency room and the interval between ultrasound and operating room. During this period 55 boys underwent exploration after preoperative scrotal Doppler ultrasound revealed absent diastolic flow and/or color flow Doppler in the symptomatic testis. Assessment of parenchymal echogenicity revealed heterogeneity in 37 testes (67%), of which none were deemed viable at exploration. Orchiectomy was performed in 34 of 37 cases. Pathological examination revealed necrosis in all 34 cases, a finding consistent with late torsion. The remaining 3 testes underwent orchiopexy by parental directive despite nonviability, as confirmed by biopsy and subsequent atrophy. Thus, heterogeneity on preoperative ultrasound was universally predictive of organ loss (chi-square p <0.001). Of the 18 symptomatic testes (33%) demonstrating homogeneity and isoechogenicity on ultrasound 16 (89%) were deemed viable at exploration. Boys in whom the torsed testicle was nonviable on exploration experienced an average of 27.5 hours of pain preoperatively (range 5 to 72), whereas boys in whom the torsed testis was salvaged experienced an average of 20.5 hours of pain (range 2 to 96) (p = 0.073). The nonviable group underwent surgery an average of 49 minutes after ultrasound, whereas the viable group underwent surgery 52 minutes after ultrasound (p = 0.92). None of the 55 patients experienced any surgical or anesthetic complications and no pathological condition was noted intraoperatively in the contralateral asymptomatic testis. In the setting of Doppler proven testicular torsion heterogeneous parenchymal echo texture indicates late torsion and testicular nonviability. Therefore, the case may not require emergent scrotal exploration. On the other hand, homogeneous echo texture portends extremely well for testicular viability. Thus, such testes should be explored emergently.

Feasibility of Using Near-Infrared Spectroscopy to Diagnose Testicular Torsion: An Experimental Study in Sheep

To assess whether near-infrared spectroscopy can detect testicular hypoxia in a sheep model of testicular torsion within 6 hours of experimental torsion. This was a randomized, controlled, nonblinded study. Trans-scrotal, near-infrared, spectroscopy-derived testicular tissue saturation of oxygen values were obtained from the posterior hemiscrota of 6 anesthetized sheep at baseline and every 15 minutes for 6 hours after either experimental-side, 720-degree, unilateral, medial testicular torsion and orchidopexy or control-side sham procedure with orchidopexy and then for 75 minutes after reduction of torsion and pexy. Color Doppler ultrasonography was performed every 30 minutes to confirm loss of vascular flow on the experimental side, return of flow after torsion reduction, and preserved flow on the control side. Near infrared spectroscopy detected a prompt, sustained reduction in testicular tissue saturation of oxygen after experimental torsion. Further, it documented a rapid return of these values to pretorsion levels after reduction of torsion. Experimental-side testicular tissue saturation of oxygen fell from a median value of 59% (interquartile range [IQR] 57% to 69%) at baseline to 14% (IQR 11% to 29%) at 2.5 hours of torsion, and postreduction values were approximately 70%. Control-side testicular tissue saturation of oxygen values increased from a median value of 67% (IQR 59% to 68%) at baseline to 77% (IQR 77% to 94%) at 2.5 hours and remained at approximately 80% for the entire protocol. The difference in median testicular tissue saturation of oxygen between experimental and control sides, using the Friedman test, was found to be significant (P=.017). This study demonstrates the feasibility, in a sheep model, of using near-infrared spectroscopy for the noninvasive diagnosis of testicular torsion and for quantification of reperfusion after torsion reduction. The applicability of these findings, from an animal model using complete torsion, to the clinical setting remains to be established.

Varicocèle : traiter ou ne pas traiter ? quand et comment ?

Varicoceles are dilated veins within the spermatic cord and a relatively common occurrence in men. Fortunately, the large majority of men are asymptomatic, however, a proportion of men with varicoceles can suffer from infertility and testosterone deficiency. Sperm and testosterone are produced within the testis, and any alteration to the testicular environment can negatively affect the cells responsible for these processes. The negative impact of varicoceles on testicular function occurs mainly due to increased oxidative stress within the testicular parenchyma which is thought to be caused by scrotal hyperthermia, testicular hypoxia, and blood-testis barrier disruption. Management of varicoceles involves ligation or percutaneous embolization of the dilated veins. Repair of varicoceles can improve semen parameters and fertility, along with serum testosterone concentration. In this review, we discuss the pathophysiology of varicoceles, their impact on testicular function, and management.

Torsion of only spermatic cord in the absence of testis and/or epididymis results in contralateral testicular hypoxia.

Unilateral spermatic cord torsion in the presence or absence of ipsilateral testis causes hypoxia in the contralateral testis. An experimental study was conducted to find the most important structure that causes contralateral testicular hypoxia following ipsilateral twisting. In five groups each consisting of 10 rats sham operations, epididymoorchiectomy, spermatic cord torsion, spermatic cord torsion following subepididymal orchiectomy or spermatic cord torsion following epididymoorchiectomy were performed. Lactic acid, hypoxanthine and thiobarbituric acid reactive products of lipid peroxidation (TBAR) were determined in the contralateral testis. While lactic acid, hypoxanthine and TBAR values did not differ significantly following sham and epididymoorchiectomy procedures, evaluation of other groups revealed significantly increased values compared with sham and epididymoorchiectomy groups. Since torsion of only spermatic cord and testicular vasculature causes contralateral testicular hypoxia, testis and epididymis do not seem to be mandatory for occurrence of contralateral testicular hypoxia. Testicular artery under distress seems to be the most important structure that results in contralateral testicular hypoxia following torsion.

Tissue hypoxia in ipsilateral and contralateral testes undergoing surgically induced maldescent.

The mechanism of deterioration of ipsilateral and contralateral testes during unilateral maldescent remains controversial. Proposing that alterations in tissue perfusion may play a role in ipsilateral and contralateral testicular deteriorations, an experimental study has been planned to evaluate the status of parameters of tissue hypoxia in ipsilateral and contralateral testes following surgically induced maldescent, in rats which preoperatively underwent placebo or chemical sympathectomy. 60 male albino rats were used for the experiment. At the age of 21 days each 30 rats that were treated by placebo or chemical sympathectomy agent were divided into 3 groups undergoing sham operation, abdominal fixation of one testis or abdominal fixation of both testes. At the age of 3 months the rats underwent bilateral orchidectomies and lactic acid (LA) and hypoxanthine (HX) levels were measured in testicular tissues. Maldescent of the testis resulted in a marked increase of LA and HX values in the ipsilateral testis compared to controls, and also resulted in increased levels of LA and HX in the contralateral testis. Although the levels of LA and HX were lower compared to ipsilateral undescended counterparts the levels in contralateral testis were significantly elevated compared to the contralateral testes of rats undergoing sham operation following placebo treatment. Bilateral maldescent resulted in similar elevations of LA and HX in both of the testes. Administration of 6-hydroxydopamine did not result in decreased levels of LA and HX values in the ipsilateral testis following unilateral testicular undescendence. However the LA levels in the contralateral descended testis did not reveal a significant difference compared to the contralateral testis of rats undergoing sham operation. The present experimental design reveals that abdominal fixation of the testis results in tissue hypoxia not only in the ipsilateral but also in the contralateral testis. Chemical sympathectomy has some protective effects on contralateral testicular hypoxia during unilateral maldescent. Tissue hypoxia during maldescent may result from relative inadequacy of testicular blood flow to overcome the increased metabolic demands under hyperthermic conditions.

Biochemical Changes in Testicular Varicocele

The precise mechanism of the hypospermatogenesis associated with varicocele has remained uncertain, although there have been a number of speculations on the etiology of the associated infertility. The altered spermatogenesis has been attributed to the reflux of toxic metabolites from either adrenal or renal origin, disturbed hormone status, spermatic venous hypertension, testicular hypoxia secondary to stasis, and abnormal temperature regulation. However, the biochemical changes of the testicular tissue with varicocele have been only partially explored. This overview includes the available information on the biochemical change in the testes associated with varicocele as well as the introduction of basic biochemical aspects on the testes, which may give new insights into the possible pathophysiological mechanism of male infertility.

A bioenergetic model of gossypol action: effects of gossypol on adult rat spermatogenic cells.

Rat spermatogenic cells have glycolytic rates of 124 +/- 36 nmol lactate.mg protein-1.h-1. Maximum glycolytic rates in the absence of oxidative phosphorylation do not exceed the basal rates by greater than 40%. From the rates of oxygen consumption and lactate production it can be calculated that less than 8% of the total ATP produced by spermatogenic cells is provided by glycolysis. These properties of spermatogenic cells would render them highly susceptible to cytotoxicity due to the action of agents like gossypol that impair mitochondrial oxidative phosphorylation or to conditions that produce testicular hypoxia. The main effect of gossypol on spermatogenic cell energy metabolism is to uncouple mitochondrial oxidative phosphorylation. In the absence of glucose, this uncoupling action of gossypol would change the NAD+/NADH redox coupling and, consequently, could modify metabolic fluxes through the lactic dehydrogenase catalyzed reaction.