Intratesticular Testosterone Levels Research Articles

An update on male infertility and intratesticular testosterone-insight into novel serum biomarkers.

Intratesticular testosterone is vital for spermatogenesis, male fertility, and virility. Currently the only method to assess levels of intratesticular testosterone is to perform testicular biopsy which is invasive and can lead to several complications. Approaches to assess intratesticular testosterone have been understudied but hold promise as future male contraceptive agents and maygrant the ability to monitor patients undergoing hormonal changes from therapeutic and diagnostic perspectives. Previous studies have sought to assess the utility of 17-hydroxyprogesterone (17-OHP) and insulin-like factor 3 (INSL3) as accurate surrogate biomarkers of intratesticular testosterone. The aim of this review is thus to highlight the importance of intratesticular testosterone and the consequent advances that have been made to elucidate the potential of biomarkers for intratesticular testosterone in the context of male infertility.

Venlafaxine-induced adrenergic signaling stimulates Leydig cells steroidogenesis via Nur77 overexpression: A possible role of EGF

Venlafaxine, a norepinephrine and serotonin reuptake inhibitor, impairs rat sperm parameters, spermatogenesis and causes high intratesticular estrogen and testosterone levels, indicating that Leydig cells (LCs) may be a venlafaxine target. We evaluated the effect of venlafaxine treatment on rat LCs, focusing on adrenergic signaling, EGF immunoexpression and steroidogenesis. Germ cells mitotic/meiotic activity and UCHL1 levels were also evaluated in the seminiferous epithelium. Eighteen adult male rats received 30 mg/kg of venlafaxine (n = 9) or distilled water (n = 9). The seminiferous tubules, epithelium and LCs nuclear areas were measured, and the immunoexpression of Ki-67, UCHL1, StAR, EGF, c-Kit and 17β-HSD was evaluated. UCHL1, StAR and EGF protein levels and Adra1a, Nur77 and Ndrg2 expression were analyzed. Malondialdehyde (MDA) and nitrite testicular levels, and serum estrogen and testosterone levels were measured. Venlafaxine induced LCs hypertrophy and Ndrg2 upregulation in parallel to increased number of Ki-67, c-Kit- and 17β-HSD-positive interstitial cells, indicating that this antidepressant stimulates LCs lineage proliferation and differentiation. Upregulation of Adra1a and Nur77 could explain the high levels of StAR and testosterone levels, as well as aromatization. Enhanced EGF immunoexpression in LCs suggests that this growth fact is involved in adrenergically-induced steroidogenesis, likely via upregulation of Nur77. Slight tubular atrophy and weak Ki-67 immunoexpression in germ cells, in association with high UCHL1 levels, indicate that spermatogenesis is likely impaired by this enzyme under supraphysiological estrogen levels. These data corroborate the unchanged MDA and nitrite levels. Therefore, venlafaxine stimulates LCs steroidogenesis via adrenergic signaling, and EGF may be involved in this process.

MP21-04 SUCCESSFUL SPERM RETRIEVAL FOR MEN WITH Y CHROMOSOME AZFC MICRODELETION

You have accessJournal of UrologyInfertility: Epidemiology & Evaluation I (MP21)1 Sep 2021MP21-04 SUCCESSFUL SPERM RETRIEVAL FOR MEN WITH Y CHROMOSOME AZFC MICRODELETION I-Shen Huang, Wei-Jen Chen, and William J Huang I-Shen HuangI-Shen Huang More articles by this author , Wei-Jen ChenWei-Jen Chen More articles by this author , and William J HuangWilliam J Huang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002006.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Among the genetic aberrations contributing to male infertility, the deletion of the AZFc region of the Y chromosome is a common cause of spermatogenetic failure and the chances for successful surgical sperm extraction from azoospermic men with AZFc region microdeletion are relatively good. Nevertheless, it is still a challenge to procure sperm from a sizeable proportion of individuals with AZFc microdeletion, even when meticulous surgical measures are employed. The objective of this study is to identify predictive factors for successful sperm retrieval in men with AZFc microdeletion. METHODS: 76 infertile men were studied, each having Y chromosome AZFc microdeletion at some time during a 10-year period, as confirmed by multiplex polymerase chain reaction (PCR) amplification of STS (sequence tagged site). For each patient, the endocrine profile including serum follicle stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), prolactin (PRL) and estradiol (E2) was recorded, along with intratesticular testosterone level (ITT), age and testicular size. The factors were further analyzed to determine the key predictors for successful sperm retrieval. RESULTS: Of the 76 men with AZFc microdeletion, 56 were classified as having non-obstructive azoospermia (NOA), 8 as having cryptozoospermia, and 12 as having severe oligoasthenoteratozoospermia (OAT). Of the 56 men with azoospermia, 50 received microdissection TESE (mTESE), and sperm retrieval was successful in 37 of those cases (74 %). A significantly lower serum FSH (P = 0.02) was found in those patients from whom sperm could be successfully retrieved. On the other hand, parameters such as levels of LH, TT, PRL, E2, testicular volume and age were not found to be correlated with successful sperm recovery. The area under the receiving operating characteristic (ROC) curve (AUC) for FSH was determined to be 0.721. Using an FSH cut-off point of 12.95 mIU/mL according to Youden’s index, the model for predicting successful sperm retrieval was found to have 51.4% sensitivity, 84.6% specificity, 90.5% positive predictive value (PPV) and 37.9% negative predictive value (NPV). CONCLUSIONS: Men exhibiting AZFc microdeletion with discernible spermatogenesis from whom sperm was successfully retrieved by mTESE generally presented with relatively lower FSH levels. Source of Funding: nil © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e347-e347 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information I-Shen Huang More articles by this author Wei-Jen Chen More articles by this author William J Huang More articles by this author Expand All Advertisement Loading ...

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.

Effect of Sorafenib on Sex Hormone Levels in Male Swiss Albino Mice

Background: Hormones play a vital role in initiating and maintenance of male reproductive or testicular function which includes the production of androgens and spermatozoa. Testosterone is essential for the initiation and maintenance of spermatogenesis. FSH is responsible for the stimulation of spermatogenesis. Semen analysis and hormone evaluation are essential parameters in the diagnosis of infertility in males. Objective: The aim of the present study is to evaluate the effect of sorafenib on FSH and intratesticular testosterone levels in male Swiss albino mice. Materials and Methods: The animals were segregated into control, positive control, and treatment groups (n=6). Treatment group received 25, 50 and 100 mg/kg body weight of sorafenib orally for seven consecutive days at intervals of 24 hours between two administrations. Positive control group received 100 mg/kg body weight of imatinib. The animals were sacrificed at the end of 1st, 2nd, 4th, 5th, 7th and 10th week after the last exposure to sorafenib. Results: The intratesticular testosterone level was significantly (P&lt;0.05) reduced in treated groups and severe effect was observed on week 4th and 5th weeks. FSH level was increased significantly (P&lt;0.05) in sorafenib treated groups of mice. Conclusion: The administration of sorafenib does affect testosterone and FSH level significantly, but this effect is reversible once the drug is withdrawn. This finding may help the clinicians to plan and address the fertility-related issues in young patients of reproductive age who are being treated with sorafenib for advanced renal cell carcinoma, hepatocellular carcinoma and differentiated thyroid carcinoma.

Low Doses of Glyphosate/Roundup Alter Blood-Testis Barrier Integrity in Juvenile Rats.

It has been postulated that glyphosate (G) or its commercial formulation Roundup (R) might lead to male fertility impairment. In this study, we investigated the possible effects of G or R treatment of juvenile male rats on blood-testis barrier function and on adult male sperm production. Pups were randomly assigned to the following groups: control group (C), receiving water; G2 and G50 groups, receiving 2 and 50 mg/kg/day G respectively; and R2 and R50 groups receiving 2 and 50 mg/kg/day R respectively. Treatments were performed orally from postnatal day (PND) 14 to 30, period of life that is essential to complete a functional blood-testis barrier. Evaluation was done on PND 31. No differences in body and testis weight were observed between groups. Testis histological analysis showed disorganized seminiferous epithelium, with apparent low cellular adhesion in treated animals. Blood-testis barrier permeability to a biotin tracer was examined. A significant increase in permeable tubules was observed in treated groups. To evaluate possible mechanisms that could explain the effects on blood-testis barrier permeability, intratesticular testosterone levels, androgen receptor expression, thiobarbituric acid reactive substances (TBARS) and the expression of intercellular junction proteins (claudin11, occludin, ZO-1, connexin43, 46, and 50 which are components of the blood-testis barrier) were examined. No modifications in the above-mentioned parameters were detected. To evaluate whether juvenile exposure to G and R could have consequences during adulthood, a set of animals of the R50 group was allowed to grow up until PND 90. Histological analysis showed that control and R50 groups had normal cellular associations and complete spermatogenesis. Also, blood-testis barrier function was recovered and testicular weight, daily sperm production, and epididymal sperm motility and morphology did not seem to be modified by juvenile treatment. In conclusion, the results presented herein show that continuous exposure to low doses of G or R alters blood-testis barrier permeability in juvenile rats. However, considering that adult animals treated during the juvenile stage showed no differences in daily sperm production compared with control animals, it is feasible to think that blood-testis barrier impairment is a reversible phenomenon. More studies are needed to determine possible damage in the reproductive function of human juvenile populations exposed to low doses of G or R.

Diabetes Type 1 Negatively Influences Leydig Cell Function in Rats, Which is Partially Reversible By Insulin Treatment.

Type 1 diabetes mellitus (T1DM) is associated with impaired spermatogenesis and lower testosterone levels and epididymal weight. However, the underlying processes in the testis are unknown and remain to be elucidated. Therefore, the present study focused on the effects of T1DM on testicular function in a spontaneously diabetic rat model. BB/OKL rats after diabetes manifestation were divided into 3 groups: those without insulin treatment and insulin treatment for a duration of 2 and of 6 weeks. Anthropometrical data, circulating levels of gonadotrophins, testosterone, and inhibin B were measured. Intratesticular testosterone, oxidative stress, inflammation, and apoptosis were analyzed. Key enzymes of steroidogenesis were evaluated in the testis. Untreated diabetic rats had significantly lower serum follicle-stimulating hormone and luteinizing hormone levels. Serum and intratesticular testosterone levels significantly decreased in untreated diabetic rats compared to healthy controls. Key markers of Leydig cell function were significantly downregulated at the RNA level: insulin-like factor 3 (Insl3) by 53% (P = .006), Star by 51% (P = .004), Cyp11A1 by 80% (P = .003), 3Beta-Hsd2 by 61% (P = .005), and Pbr by 52% (P = .002). In the insulin-treated group, only Cyp11A1 and 3Beta-Hsd2 transcripts were significantly lower. Interestingly, the long-term insulin-treated group showed significant upregulation of most steroidogenic enzymes without affecting testosterone levels. Tumor necrosis factor α and apoptosis were significantly increased in the long-term insulin-treated rats. In conclusion T1DM, with a severe lack of insulin, has an adverse action on Leydig cell function. This is partially reversible with well-compensated blood glucose control. Long-term T1DM adversely affects Leydig cell function because of the process of inflammation and apoptosis.

Association of aging and obesity with decreased 17-hydroxyprogesterone, a serum biomarker of intratesticular testosterone.

Obesity's negative association with serum testosterone can be explained by either decreasing luteinizing hormone (LH) production from the pituitary gland and/or directly impacting intratesticular testosterone production. We hypothesize that obesity will negatively impact intratesticular testosterone levels when compared to those of non-obese men. We performed a cross-sectional analysis of men with symptoms of testosterone deficiency and male infertility between July 2018 and April 2020 to evaluate the association between body mass index (BMI) and age with intratesticular testosterone (using serum 17-hydroxyprogesterone (17-OHP) as a biomarker), and between BMI with LH. Univariable and multiple linear regression analysis were performed using confounding variables to predict 17-OHP and testosterone. A total of 340 men were selected. Median age was 38 [33-44] years, BMI 27.8 [25.4-31.1] kg/m2, serum testosterone 363 [256.3-469.6] ng/dl, 17-OHP 60.5 [39.3-85.8] ng/dl, and LH 4.2 [2.8-5.7] mIU/ml. Older and obese men had lower testosterone compared to younger and non-obese men. Interestingly, increasing age and higher BMI were associated with lower 17-OHP (p < 0.001). Contrarily, age and BMI were not associated with LH levels (p = 0.478). In conclusion, obesity and aging negatively affected 17-OHP independent of LH, suggesting a possible direct effect on testicular function, rather than a secondary effect from a decline in pituitary signaling.

Venlafaxine-induced damage to seminiferous epithelium, spermiation, and sperm parameters in rats: A correlation with high estrogen levels.

Venlafaxine (selective serotonin and norepinephrine reuptake inhibitor) use has increased worldwide. However, the impact of venlafaxine on testes and sperm parameters has not been investigated. We evaluated venlafaxine impact on testicular and sperm parameters and verified whether the changes are reversible. Animals from venlafaxine-35days and venlafaxine-65days groups received 30mg/kg of venlafaxine for 35days. Control-35days and control-65days received distilled water. In control-65days and venlafaxine-65days, the treatment was interrupted for 30days. Sperm concentration, morphology, motility, and mitochondrial activity were analyzed. Number of step 19 spermatids (NLS), frequency of tubules with spermiation failure, Sertoli cells number, and TUNEL-positive germ cells were quantified. Testicular aromatase, connexin 43 (Cx43) immunoexpression, Cx43 protein levels, and Cx43 expression were evaluated. Either intratesticular testosterone or estrogen levels were measured. Venlafaxine impaired sperm morphology, reduced sperm concentration, mitochondrial activity, and sperm motility. The frequency of tubules with spermiation failure and NLS increased in parallel to increased Cx43 immunoexpression; mRNA and protein levels; and aromatase, testosterone, and estrogen levels. An increase in germ cell death and decreased Sertoli cells number were observed. In venlafaxine-65days, except for sperm motility, mitochondrial activity, Sertoli cells number, and germ cell death, all other parameters were partially or totally recovered. Venlafaxine increases testosterone aromatization and Cx43. This drug, via high estrogen levels, disturbs Sertoli cells, induces germ cell death, and impairs spermiation and sperm parameters. The restoration of spermiation associated with the decreased Cx43 and hormonal levels in venlafaxine-65days reinforces that high estrogen levels are related to venlafaxine-induced changes. The presence of damaged Sertoli cells, germ cell death, and low sperm motility in venlafaxine-65days indicates that interruption of treatment for 30days was insufficient for testicular recovery and points to a long-term estrogen impact on the seminiferous epithelium.

Testicular blood supply is altered in the 41,XXY* Klinefelter syndrome mouse model

Hypergonadotropic hypogonadism is a major feature of Klinefelter syndrome (KS), assumed to be caused by testicular hormone resistance. It was previously shown that intratesticular testosterone levels in vivo and Leydig cell function in vitro seem to be normal indicating other functional constraints. We hypothesized that impaired testicular vascularization/blood flow could be a co-factor to the observed hypergonadotropic hypogonadism. We evaluated the testicular vascular system by measuring blood vessel sizes during postnatal development and testis blood flow in adult 41,XXY* mice. Proportional distribution and size of blood vessels were analyzed during testicular development (1, 3, 5, 7, 10, 21 dpp, 15 wpp). While ratios of the vessel/testis area were different at 15 wpp only, a lower number of smaller and mid-sized blood vessels were detected in adult KS mice. For testicular blood flow determination we applied contrast enhanced ultrasound. Floating and reperfusion time for testicular blood flow was increased in 41,XXY* mice (floating: XY* 28.8 ± 1.69 s vs XXY* 44.6 ± 5.6 s, p = 0.0192; reperfusion XY* 19.7 ± 2.8 s vs XXY*: 29.9 ± 6.2 s, p = 0.0134), indicating a diminished blood supply. Our data strengthen the concept that an impaired vascularization either in conjunction or as a result of altered KS testicular architecture contributes to hormone resistance.

Cyperus esculentusL. (tigernut) mitigates high salt diet‐associated testicular toxicity in Wistar rats by targeting testicular steroidogenesis, oxidative stress and inflammation

High salt diet (HSD) impairs testicular function via oxidative stress. Cyperus esculentus contains antioxidants and improves testicular function. We investigated the protective effect of hydro-ethanolic extract of Cyperus esculentus on testicular function in HSD-fed Wistar rats. Twenty-five male Wistar rats (125-135g) 8-9weeks old were divided into five groups (n=5): control, HSD-fed (8% NaCl in feed), extract-treated (500mgkg-1 day-1 ), HSD-fed +500mgkg-1 day-1 of extract and HSD-fed +1,000mgkg-1 day-1 of extract groups. Treatment lasted for 6weeks. HSD decreased (p<.05) sperm parameters and serum reproductive hormones levels, while Cyperus esculentus extract improved (p<.05) sperm parameters, and serum testosterone and follicle-stimulating hormone levels in HSD-fed rats. The extract upregulated intra-testicular testosterone level and activities of 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-HSD, downregulated malondialdehyde and nitric oxide levels, and exhibited a dose-dependent decrease in pro-inflammatory cytokines, upregulation of activities of enzymatic antioxidants and increase in total antioxidant capacity in testes of HSD-fed rats. The extract at both doses improved Johnsen's score, Leydig and Sertoli cell counts and seminiferous tubular diameter in HSD-fed rats. Cyperus esculentus exhibited a dose-dependent mitigation of HSD-associated testicular dysfunction by targeting testicular steroidogenesis, oxidative stress and inflammation.

Orlistat attenuates obesity‐induced decline in steroidogenesis and spermatogenesis by up‐regulating steroidogenic genes

Steroidogenesis decline is reported to be one of the mechanisms associated with obesity-induced male factor subfertility/infertility. We explored the possible preventive/therapeutic effects of orlistat (a medication prescribed for weight loss) on obesity-induced steroidogenesis and spermatogenesis decline. Twenty-four adult male Sprague Dawley rats weighing 250-300g were randomized into four groups (n=6/group), namely; normal control, high-fat diet, high-fat diet plus orlistat preventive group and high-fat diet plus orlistat treatment group. Orlistat (10mg/kg/b.w./d suspended in distilled water) was either concurrently administered with high-fat diet for 12weeks (high-fat diet plus orlistat preventive group) or administered from week 7-12 post- high-fat diet feeding (high-fat diet plus orlistat treatment group). Thereafter, serum, testes and epididymis were collected for analyses. Obesity increased serum leptin and decreased adiponectin levels, decreased serum and intra-testicular levels of follicle stimulating hormone, luteinising hormone and testosterone, sperm count, motility, viability, normal morphology and epididymal antioxidants, but increased epididymal malondialdehyde level and sperm nDNA fragmentation. Testicular mRNA transcript levels of androgen receptor, luteinizing hormone receptor, steroidogenic acute regulatory protein, cytochrome P450 enzyme (CYP11A1), 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase were significantly decreased in the testes of the high-fat diet group. Further, the levels of steroidogenic acute regulatory protein protein and enzymatic activities of CYP11A1, 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase were also significantly decreased in the testes of the high-fat diet group. Treatment with orlistat significantly decreased leptin and increased adiponectin levels, improved sperm parameters, decreased sperm DNA fragmentation, increased the levels of steroidogenic hormones, proteins and associated genes in high-fat diet-induced obese male rats, with the preventive group (high-fat diet plus orlistat preventive group) having better results relative to the treatment group (high-fat diet plus orlistat treatment group). Orlistat attenuated impaired spermatogenesis and steroidogenesis decline by up-regulating steroidogenic genes. This may not be unconnected to its significant effect in lowering serum leptin levels, since the hormone is known to dampen fertility potential. Therefore, orlistat may improve fertility potential in overweight/obese men.

Testosterone Supplementation Rescues Spermatogenesis and In Vitro Fertilizing Ability of Sperm in Kiss1 Knockout Mice.

Restoration of spermatogenesis and fertility is a major issue to be solved in male mammals with hypogonadotropic hypogonadism. Kiss1 knockout (KO) male mice are postulated to be a suitable animal model to investigate if hormonal replacement rescues spermatogenesis in mammals with this severe reproductive hormone deficiency, because KO mice replicate the hypothalamic disorder causing hypogonadism. The present study investigated whether testosterone supplementation was able to restore spermatogenesis and in vitro fertilization ability in Kiss1 KO mice. To this end, spermatogenesis, in vitro fertilization ability of Kiss1 KO sperm, and preimplantation development of wild-type embryos inseminated with Kiss1 KO sperm, were examined. The newly generated Kiss1 KO male mice showed infertility with cryptorchidism. Subcutaneous testosterone supplementation for 6 weeks restored plasma and intratesticular testosterone levels, elicited testicular descent, and induced complete spermatogenesis from spermatocytes to elongated spermatids in the testis, resulting in an increase in epididymal sperm number in testosterone-supplemented Kiss1 KO male mice. Epididymal sperm derived from the testosterone-supplemented Kiss1 KO mice showed normal in vitro fertilization ability, and the fertilized eggs showed normal preimplantation development, while the males failed to impregnate females. These results suggest that the failure of spermatogenesis in Kiss1 KO mice is mainly due to a lack of testosterone production, and that Kiss1 KO sperm are capable of fertilizing eggs if the animals receive the appropriate testosterone supplementation without local kisspeptin signaling in the testis and epididymis. Thus, testosterone supplementation would restore spermatogenesis of male mammals showing hypogonadotropic hypogonadism with genetic inactivation of the KISS1/Kiss1 gene.

Effect of microsurgical varicocelectomy on semen parameters, serum, and intratesticular testosterone levels.

ObjectiveThe goal of this work was to evaluate if men who underwent microsurgical varicocelectomy would have improvement in serum testosterone (T) as well as serum 17‐hydroxyprogesterone (17‐OHP—An intratesticular T biomarker) in addition to semen parameters after operation.Materials and MethodsWe conducted a prospective analysis of 30 men who underwent microsurgical varicocelectomy from December 2018 to September 2019. We assessed varicocele grade and laterality, serum T, serum 17‐OHP, serum follicle‐stimulating hormone (FSH), serum LH, and semen parameters in baseline and follow‐up. According to the data distribution, we reported the median and interquartile ranges and utilized the Mann‐Whitney U, Student's t test and Wilcoxon rank test. Correlation analysis was performed with the Spearman test.ResultsIn the baseline, 9 (30%) men had 17‐OHP < 55 ng/dL and 21 (70%) men presented with 17‐OHP ≥ 55 ng/dL. Also, 19 men had TMSC < 9 million, including 6 men with azoospermia, 1 man with cryptozoospermia, and 11 men with TMSC ≥ 9 million. We found an improvement in most SA parameters of most men, which include concentration (63.3%, 19/30), motility (46.6%, 14/30), and TMSC (60%, 18/30). About seven (36.8%) men had TMSC upgraded to > 9. There was a significant change in volume (2.1 [1.5‐2.8] to 2.4 [1.7‐3.6] cc, P = .018), concentration (6.8 [0.8‐22.5] to 12.5 [1‐31] million/cc, P = .047) and TMSC (4.4 [0.3‐15.1] to 10.5 [0‐41.8] million, P = .012) after surgery. We neither found a change in serum T nor a change in intratesticular T (serum 17‐OHP) after varicocelectomy (P > .05). FSH, LH and T were similar both before and after varicocelectomy (P > .05).ConclusionDespite improvement in semen parameters following varicocelectomy, we did not see changes in either serum or intratesticular T. This suggests that improvement of semen parameters following varicocele repair could be from factors other than changes in androgen levels within the testis.

MP78-02 CAN WE USE SERUM 17-HYDROXYPROGESTERONE AS A SERUM BIOMARKER OF INTRATESTICULAR TESTOSTERONE?

You have accessJournal of UrologySexual Function/Dysfunction: Evaluation II (MP78)1 Apr 2020MP78-02 CAN WE USE SERUM 17-HYDROXYPROGESTERONE AS A SERUM BIOMARKER OF INTRATESTICULAR TESTOSTERONE? Thiago Lima*, Premal Patel, Ruben Blachman-Braun, Vinayak Madhusoodanan, and Ranjith Ramasamy Thiago Lima*Thiago Lima* More articles by this author , Premal PatelPremal Patel More articles by this author , Ruben Blachman-BraunRuben Blachman-Braun More articles by this author , Vinayak MadhusoodananVinayak Madhusoodanan More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000964.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Intratesticular testosterone (ITT) is essential for spermatogenesis and can only be reliably measured with invasive testicular sampling. Previous studies showed good correlation between ITT and serum 17-hydroxyprogesterone (17-OHP) in men treated with human Chorionic Gonadotropin (hCG). Based on this observation, we hypothesized that we can use serum 17-OHP as a serum biomarker for ITT in men receiving testosterone therapies. METHODS: We performed a prospective study from July 2018 to October 2019. We evaluated men undergoing agents that alter serum testosterone at baseline and after 3 months of therapy. The control group comprised of fertile men who had never received testosterone therapy. According to the data distribution, we reported the median and interquartile ranges [25-75] and utilized the Mann Whitney U or Wilcoxon tests. RESULTS: On an initial cross-sectional analysis, we evaluated 42 fertile controls, 37 men receiving Clomiphene Citrate (CC) and/or human Chorionic Gonadotropin (hCG) and 21 that received exogenous testosterone therapy (TRT). We demonstrated that serum testosterone levels were similar between men receiving the various therapies, however we found that serum 17-OHP was undetectable in men that received TRT compared to men receiving CC/hCG or fertile controls (Figure 1). Furthermore, on a prospective evaluation in men who received testosterone altering therapies, we demonstrated that serum 17-OHP decreased in men who received TRT (p < 0.05) at 3 months as compared to men who received CC/hCG (Figure 2) in whom serum 17-OHP was maintained. CONCLUSIONS: Serum 17-OHP appears to be a reliable serum marker for ITT levels. Serum 17-OHP could potentially be used in the management of men with hormonal causes of infertility, titrating and altering medications based on ITT levels rather than serum testosterone levels. Source of Funding: None. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1173-e1173 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Thiago Lima* More articles by this author Premal Patel More articles by this author Ruben Blachman-Braun More articles by this author Vinayak Madhusoodanan More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF downloadLoading ...

Evaluation of antioxidant capacity and reproductive toxicity of aqueous extract of Thai Mucuna pruriens seeds

ObjectiveIn traditional medicine, the seeds of Thai Mucuna pruriens (T-MP) are used to treat male dysuria and are believed to enhance fertility. However, information pertaining to the toxicity of T-MP and its interaction with other properties is limited. This study was thus conducted to evaluate the antioxidant capacity and subacute toxicity of T-MP in the reproductive system. MethodsTotal phenolic content and antioxidant capacity of T-MP seed extract were determined using total phenolic content, 2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power assays. Male and female adult rats were treated orally with T-MP at a dosage of 150 or 300 mg/kg body weight for 14 consecutive days. Sex hormones and functional parameters in the liver and kidney were evaluated. Histopathology of all tissue was conducted using Masson’s trichrome staining. Sperm parameters, including concentration, morphology, acrosome reaction status and DNA damage, were also examined. Expression of tyrosine phosphorylated protein (TyrPho), androgen receptor and A-kinase-anchoring protein 4 (AKAP4) were investigated using the Western blot technique. ResultsT-MP seed extract contained phenolic compounds and exhibited high antioxidant capacity with no toxicity at the tested doses. It did not affect liver or kidney function parameters in the male rats, but increased estradiol, aspartate aminotransferase and alanine aminotransferase levels in the females. Additionally, it decreased serum progesterone and alkaline phosphatase levels in female rats. Serum and intratesticular testosterone levels were significantly lower in male rats that received a high dosage of T-MP. Histopathological changes were not observed in any tissue treated with T-MP. T-MP also significantly increased sperm concentration (but did not affect sperm parameters), and enhanced testicular TyrPho protein and androgen receptor and expression of AKAP4 in sperms. ConclusionT-MP seed extract exhibited antioxidant capacity and was not harmful to reproductive tissues. It also had a phytoestrogenic effect on females and increased the expression of testicular and sperm markers of male fertility.

Serum 17-Hydroxyprogesterone is a Potential Biomarker for Evaluating Intratesticular Testosterone.

Intratesticular testosterone is essential for spermatogenesis and can only be reliably measured with invasive testicular sampling. Previous studies have demonstrated good correlation between intratesticular testosterone and serum 17-hydroxyprogesterone (17-OHP) in men treated with human chorionic gonadotropin. Based on this observation we hypothesized that we can use serum 17-OHP as a serum biomarker for evaluating intratesticular testosterone in men receiving medications that alter serum testosterone. Initially, we conducted a cross-sectional analysis of men with a single serum 17-OHP evaluation from July 2018 to March 2019. We followed this with a prospective analysis from July 2018 to October 2019 with evaluation of 140 men including fertile controls, and those receiving treatments that alter serum testosterone at baseline and after 3 months of therapy. According to the data distribution, we reported the median and interquartile ranges, and used the Mann Whitney U or Wilcoxon tests. In the initial cross-sectional analysis of 93 men, a total of 30 men received treatments that increase or maintain intratesticular testosterone concentrations, such as clomiphene citrate and/or human chorionic gonadotropin; 21 men received treatments that suppress intratesticular testosterone concentrations (various exogenous testosterone replacement therapy formulations) and 42 fertile men with normal serum testosterone (greater than 300 ng/dl) were used as control. We demonstrated that serum testosterone levels were within normal range among men receiving the various therapies. In contrast, we found that serum 17-OHP was undetectable in men who received exogenous testosterone replacement therapy, as opposed to men receiving human chorionic gonadotropin and/or clomiphene citrate or fertile controls (p <0.05). In the prospective evaluation that ensued, 17-OHP values decreased in the 21 men who received testosterone replacement therapy (47.5 [21-70] to 13.5 [10-23] ng/dl, p <0.05). Conversely, 17-OHP increased in the 55 men who received human chorionic gonadotropin and/or clomiphene citrate when compared to their baseline levels (42 [24-72] to 88 [61-135] ng/dl, p <0.05). Serum 17-OHP appears to be a reliable serum marker for intratesticular testosterone levels and could potentially be used to titrate or change medications that alter intratesticular testosterone.

Administration of Pharmaceutical Agents Prior to Testicular Sperm Extraction Procedures: A Meaningful or Meaningless Approach?

To date, no randomized and controlled study has demonstrated the effect of adjuvant medical therapy on testicular sperm production before the sperm retrieval procedures in men with non-obstructive azoospermia (NOA). To present the available data on the administration of pharmaceutical agents prior to testicular sperm extraction (TESE) procedures in order to obtain better sperm retrieval results in men with NOA. Various pharmaceutical agents were used empirically to induce spermatogenesis in the treatment of NOA. The rationale for adjuvant hormonal treatment has been to increase intratesticular testosterone levels with different dosages of gonadotropins, anti-estrogen agents, or aromatase inhibitors. Based on the published studies, in the presence of a normal range of peripheral serum total testosterone levels, no medical treatment is advised, and TESE procedures should be performed directly in men with NOA. Further well-designed and randomized, placebo-controlled trials are needed to support the potential benefit of pretreatment prior to TESE procedures.

Malaysian propolis and metformin mitigate subfertility in streptozotocin-induced diabetic male rats by targeting steroidogenesis, testicular lactate transport, spermatogenesis and mating behaviour.

Diabetes mellitus is one of the risk factors for male subfertility/infertility. Malaysian propolis is reported to decrease hyperglycaemia in diabetic state. The present study investigated the protective effect of Malaysian propolis on diabetes-induced subfertility/infertility. Additionally, its combined beneficial effects with metformin were investigated. Forty adult male Sprague Dawley rats were randomly assigned into five groups, namely normal control, diabetic control, diabetic+Malaysian propolis (300mg/k.g. b.w.), diabetic+metformin (300mg/kg b.w.) and diabetic+Malaysian propolis+metformin. Diabetes was induced using a single intraperitoneal injection of streptozotocin (60mg/kg b.w.) and treatment lasted for 4weeks. During the 4th week, mating behavioural experiments were performed using sexually receptive female rats. Thereafter, fertility parameters were assessed in the female rats. Malaysian propolis increased serum and intratesticular free testosterone levels, up-regulated the mRNA levels of AR and luteinizing hormone receptor, up-regulated the mRNA and protein levels of StAR, CYP11A1, CYP17A1, 3β-HSD and 17β-HSD in the testes of diabetic rats. Furthermore, Malaysian propolis up-regulated testicular MCT2, MCT4 and lactate dehydrogenase type C mRNA levels, in addition to improving sperm parameters (count, motility, viability and normal morphology) and decreasing sperm nDNA fragmentation in diabetic rats. Malaysian propolis improved mating behaviour by increasing penile guanosine monophosphate levels. Malaysian propolis also improved fertility outcome as seen with decreases in pre- and post-implantation losses, increases in gravid uterine weight, litter size per dam and foetal weight. Malaysian propolis's effects were comparable to metformin. However, their combination yielded better results relative to the monotherapeutic interventions. Malaysian propolis improves fertility potential in diabetic state by targeting steroidogenesis, testicular lactate metabolism, spermatogenesis and mating behaviour, with better effects when co-administered with metformin. Therefore, Malaysian propolis shows a promising complementary effect with metformin in mitigating Diabetes mellitus-induced subfertility/infertility.

Effects of letrozole administration on growth and reproductive performance in Markhoz goat bucklings

This study evaluated the growth performance, testicular and semen characteristics, and hormonal profile of Markhoz (Iranian Angora) bucklings injected with letrozole (LTZ). Twenty-eight 4–4.5 month old bucks were randomly assigned into four groups and received either 0.25 mg/kg body weight (BW) LTZ subcutaneously (sc LTZ) or intramuscularly (im LTZ), and also sc (sc CONT) or im (im CONT) controls every week for 3 months. The study was performed at the beginning of the breeding season in Sanandaj Animal Husbandry Research Station (46.99 °E, 35.31 °N). The results showed that LTZ causes increased final body weight (25.78 ± 1.61 kg), higher average daily gain (104 ± 0.03 g/days), and decreased feed conversion ratio (7.81 ± 2.57) (P < 0.05). The pre-slaughter, hot, and cold carcass weights (27.56 ± 2.40, 11.45 ± 1.07 and 11.11 ± 1.05 kg, respectively) were (P < 0.05) heavier in LTZ groups while other carcass characteristics did not differ between groups. No differences occurred between the groups in biochemical parameters, except high-density lipoprotein levels (35.47 ± 2.43 mg/dL) which was higher in LTZ treatments (P < 0.05). LTZ-treated bucks had larger scrotal circumference (20.12 ± 5.75 cm), higher relative testicular weight (560.91 ± 78.59 mg/100 g BW) and volume (175.5 ± 29.71 cm3), greater diameter of seminiferous tubules (224.5 ± 5.21 μm), and number of Sertoli cells (8.39 ± 0.77) (P < 0.05). Semen volume (0.74 ± 0.16 mL), sperm concentration (2.64 ± 0.19 × 10−9/mL), total sperm per ejaculate (1.95 ± 0.49 × 10−9), and semen index (1248 ± 323) increased (P < 0.05) by LTZ treatments, while semen pH (6.77), motility (80.91%), progressive motility (76.75%), viability (83.35%), abnormality (13.70%), acrosome integrity (78.06%), and membrane integrity (80.05%) of sperm remained unaffected. Intratesticular and serum testosterone (T) levels (7.97 ± 0.89 ng/mg protein and 2.47 ± 0.59 ng/mL, respectively), serum luteinizing hormone (LH), growth hormone (GH) levels (1.71 ± 0.24 and 3.62 ± 0.33 ng/mL, respectively) of LTZ groups were elevated, whereas intratesticular and serum estradiol (E2) levels (84.14 ± 8.15 pg/mg protein and 32.33 ± 2.16 pg/mL, respectively) decreased (P < 0.05). No differences were recorded between the sc and im routes of LTZ administration in the measured parameters. To conclude, we have found that LTZ treatment improves growth and reproductive functions of goat bucklings associated with increased serum LH and GH, elevated T and reduced E2 levels in both serum and testis.