Leydig cell tumors of the testis are the most common type of non-germ cell testicular tumors. In adult patients, gynecomastia, oligozoospermia, erectile dysfunction, and other signs of feminization can be present, wherea...Leydig cell tumors of the testis are the most common type of non-germ cell testicular tumors. In adult patients, gynecomastia, oligozoospermia, erectile dysfunction, and other signs of feminization can be present, whereas testosterone levels are frequently in the normal range or slightly reduced. We describe a patient with a history of impaired sexual function, as well as progressive enlargement of the left testis, without gynecomastia. Hormonal evaluation demonstrated very high testosterone, estrogen, and pan-alpha-inhibin levels. Magnetic resonance imaging revealed the presence of left testicular hypertrophy without evidence of testicular mass. After left orchiectomy, histologic examination confirmed the diagnosis of Leydig cell tumor, and steroid hormone levels normalized. A heterozygous missense somatic gsp mutation (R201C) was found in tumoral tissue, whereas no mutation was found in the surrounding normal tissue or in leukocyte DNA. This case provides evidence that somatic activating gsp mutation in Leydig cells may result in tumor development, leading to overexpression of the inhibin alpha subunit and hyperactivity of the testosterone biosynthetic pathway.
The biochemical composition of seminal plasma (SP) is very complex and variable among species. Advances in reproductive technologies reveal SP as a nutritive-protective medium for sperm cells suspended in it, and some SP...The biochemical composition of seminal plasma (SP) is very complex and variable among species. Advances in reproductive technologies reveal SP as a nutritive-protective medium for sperm cells suspended in it, and some SP components are very important for sperm metabolism, as well as sperm function, survival, and transport in the female reproductive tract. Biochemistry of SP is a relatively modern but rapidly expanding field of research, particularly concerning the biological significance of the various biochemical constituents of SP. However, identification of active factors in SP and mechanisms by which they act are not sufficiently understood in different species. Especially in camelids, the origin, composition, and function of the viscous component of SP remain a mystery, and only some biochemical and morphological characteristics of SP have been described. In this review, we focus on the current understanding of physiological and biochemical properties of SP in ruminants and camelids.
Testosterone replacement therapy (TRT) can improve the symptoms, signs, and well being of hypogonadal men by restoring serum testosterone concentrations to physiologic levels. This multicenter, open-label noncomparative...Testosterone replacement therapy (TRT) can improve the symptoms, signs, and well being of hypogonadal men by restoring serum testosterone concentrations to physiologic levels. This multicenter, open-label noncomparative trial of men with hypogonadism evaluated the pharmacokinetic profile and safety of a novel testosterone 2% gel (Fortesta™ Gel), administered once daily to the front and inner thighs at starting doses of 40 mg/d. The metered-dose delivery system allowed dose adjustments in 10-mg increments between 10 and 70 mg/d. Of the 149 patients enrolled, 138 patients (92.6%) completed the study and 129 patients (86.6%) were included in the efficacy analysis. On day 90, mean testosterone concentration (C(avg) [0-24 hours] ± SD) was 438.6 ± 162.5 ng/dL. Overall, 100 (77.5%) patients achieved serum total testosterone concentrations within the normal physiologic range (≥ 300 and ≤ 1140 ng/dL). On day 90, mean testosterone C(max) (± SD) was 827.6 ± 356.5 ng/dL. On day 90, a total of 122 patients (94.6%) had C(max) levels of 1500 ng/dL or less and 2 patients (1.6%) had values between 1800 and 2500 ng/dL. Similar results for C(avg) (0-24 hours) and C(max) were observed on day 35. All enrolled patients were included in the safety analysis. Testosterone 2% gel was generally well tolerated, with the most common adverse events (AE) being mild and moderate skin reactions. There were no serious AEs related to testosterone 2% gel. Once-daily testosterone 2% gel restored levels of testosterone in more than 75% of patients, with low risk of supraphysiologic testosterone levels. Patients may find this a suitable option for TRT because of its application site and low volume.
Chronic prostatitis (CP) due to Chlamydia trachomatis (Ct) infection has a significant impact on young male fertility, and eradication of Ct infection after antibiotic therapy does not always result in recovery of semen...Chronic prostatitis (CP) due to Chlamydia trachomatis (Ct) infection has a significant impact on young male fertility, and eradication of Ct infection after antibiotic therapy does not always result in recovery of semen quality. The study aim was to evaluate the effects on fertility parameters of L-arginine, L-carnitine, acetyl-L-carnitine, and ginseng extracts (FERTIMEV) associated with prulifloxacin in patients affected by CP and oligoasthenoteratozoospermia due to Ct infection. Two hundred and six patients with proven Ct genital infection and oligoasthenoteratozoospermia were enrolled in a prospective, randomized, and controlled study. Prulifloxacin (600 mg) was administered daily for 14 days, and patients were divided into 2 groups: group A: antibiotic therapy alone; and group B: antibiotic therapy and additional therapy with FERTIMEV (1 vial daily for 6 months). Microbiological and semen parameter analyses were performed both at enrollment and after 6 months. National Institutes of Health Chronic Prostatitis Symptom Index and International Prostatic Symptom Score questionnaires were applied. Of the 206 patients, 109 were assigned to group A and 97 to group B. At the enrollment time, no differences were reported with regard to clinical, instrumental, and laboratory data. Six months after treatment, statistically significant differences were demonstrated between both groups in terms of sperm concentration (21.3 ± 13.2 millions/mL vs 11.5 ± 13.2 millions/mL) (Cohen's d = 0.61) (P < .001, df = 2, F = 62.10) and percentage of motile sperm (42.4% ± 5.2% vs 29.3% ± 11.0%) (Cohen's d = 1.52) (P < .001, df = 2, F = 91.48). In this study treatment with FERTIMEV together with prulifloxacin improved semen parameters in patients with Ct genital infection and oligoasthenoteratozoospermia compared to treatment with prulifloxacin therapy alone.
High-flow priapism most often occurs following perineal and penile trauma. We report the case of a 29-year-old man who presented with recurrent priapism and was initially treated with corporal aspiration and intracaverno...High-flow priapism most often occurs following perineal and penile trauma. We report the case of a 29-year-old man who presented with recurrent priapism and was initially treated with corporal aspiration and intracavernosal injections on multiple emergency department visits and then condition-controlled with sibutramine while on treatment for weight loss. His condition relapsed after the medication was withdrawn from the market, necessitating medical intervention.
It would be of value to evaluate whether expression levels of mRNAs playing important roles in spermatogenesis could be used as predictors of successful testicular sperm recovery by microdissection testicular sperm extra...It would be of value to evaluate whether expression levels of mRNAs playing important roles in spermatogenesis could be used as predictors of successful testicular sperm recovery by microdissection testicular sperm extraction (TESE) in patients with nonobstructive azoospermia (NOA). This study included 52 patients with NOA who underwent therapeutic sperm retrieval by micro-TESE at our institution. We measured expression levels of VASA, outer dense fiber-1 (ODF1), ODF2, and sperm mitochondria-associated cysteine-rich protein (SMCP) mRNAs in testicular tissue specimens obtained from these patients by quantitative real-time reverse transcription polymerase chain reaction. Expression patterns of these mRNAs were analyzed focusing on the outcomes of sperm retrieval by micro-TESE. There were no significant differences in age, testicular volume, and serum levels of follicle-stimulating hormone, luteinizing hormone, and testosterone between successful and unsuccessful TESE groups; however, the proportion of patients with Sertoli cell only in the successful TESE group was significantly lower than that in the unsuccessful TESE group. Additionally, expression levels of VASA, ODF1, ODF2, and SMCP mRNAs in the successful TESE group were significantly greater than those in the unsuccessful TESE group. Univariate analysis identified histological classification, VASA, ODF1, ODF2, and SMCP expressions as significant predictors of sperm retrieval, of which only VASA mRNA expression appeared to be independently related to micro-TESE outcome on multivariate analysis. These findings suggest that measurement of VASA mRNA in testis could be a useful adjunct to conventional parameters for predicting sperm retrieval by micro-TESE in patients with NOA.
Male sexual orientation has been proposed to have genetic components, but previously suggested candidate genes have all received negative results. The human sonic hedgehog (SHH) gene is located in the 7q36 region, which...Male sexual orientation has been proposed to have genetic components, but previously suggested candidate genes have all received negative results. The human sonic hedgehog (SHH) gene is located in the 7q36 region, which was linked to male sexual orientation in a previous genome-wide association study. SHH is known to play an important role in embryo patterning, and there is evidence connecting it to sexual orientation. In this study, we performed an association analysis of the SHH tag single nucleotide polymorphism rs9333613 in 361 subjects and 319 Chinese male controls. We find a significant difference in genotype and allele distribution between identified homosexuals and heterosexual control subjects, suggesting that the SHH gene could potentially be associated with male sexual orientation.
Spinal and bulbar muscular atrophy is a hereditary motor neuron disease caused by the expansion of CAG triplets in the androgen receptor. Because the length of CAG repeat is inversely related with androgen receptor funct...Spinal and bulbar muscular atrophy is a hereditary motor neuron disease caused by the expansion of CAG triplets in the androgen receptor. Because the length of CAG repeat is inversely related with androgen receptor function, patients with a longer CAG repeat are expected to have a lower incidence of prostate cancer. Here, we report an extremely rare case of high-stage prostate cancer in a patient with spinal and bulbar muscular atrophy, which responded to maximal androgen blockade therapy.
For adolescents with hypogonadism, failure to comply with a testosterone replacement therapy (TRT) regimen can be a barrier to obtaining adequate and consistent serum testosterone (T) levels. We evaluated 4 young men wit...For adolescents with hypogonadism, failure to comply with a testosterone replacement therapy (TRT) regimen can be a barrier to obtaining adequate and consistent serum testosterone (T) levels. We evaluated 4 young men with hypogonadism secondary to Klinefelter syndrome to determine if implantable pellets represented a viable treatment option for such patients. Four patients (aged 14-20 years) had previously received TRT but were not compliant. Patients initially received 4 to 10 subcutaneous T pellets with subsequent doses implanted at 3- to 4-month intervals. In all 4 patients, total and free T levels were improved at follow-up, although fluctuations between levels were inconsistent. All patients reported improvement in their energy and concentration, and parents noted improved stability of mood. The mean baseline total T level of 108.3 ng/dL increased in all patients at the time of second pellet implantation. Average total T levels were 325 to 587 ng/dL over the course of therapy. There was significant variability of serum T levels while patients were on therapy. All patients eventually received an increased number of pellets at some point in their care. Subcutaneous implantation of T pellets is a viable option for TRT in young men with Klinefelter syndrome in whom compliance is an issue. However, the requirement for repeat implantation every 3 months, increased cost of therapy and monitoring, dramatic shifts in serum total and free T concentrations, and seemingly unpredictable response requires close monitoring and careful follow up and suggests this modality of therapy may not be appropriate for a substantial number of hypogonadal patients, but this strategy warrants consideration in noncompliant patients.
The objective of this study was to investigate structural changes in the penile corpus cavernosum of prepubertal chronically stressed rats. Eight Wistar rats were assigned into the stress group (SG) and were submitted to...The objective of this study was to investigate structural changes in the penile corpus cavernosum of prepubertal chronically stressed rats. Eight Wistar rats were assigned into the stress group (SG) and were submitted to 2 hours of tube restraint daily, from the fourth to the ninth week of life. Another 7 rats were used as the control group (CG). All animals were weighed weekly. At day 64, animals were sacrificed by anesthetic overdose, blood was collected for testosterone concentration by radioimmunoassay, and penis and adrenal were collected. Adrenal mass index and testosterone serum levels were used to assess the efficacy of the stress stimulus. The surface density of connective tissue and smooth muscle fibers of corpus cavernosum were measured on Masson trichromic-stained slices. Picrosirius red-stained slices were assessed under polarized light for different types of collagen. The Student's t test was applied for mean comparisons, with P < .05 considered significant. Testosterone serum concentrations decreased and adrenal mass index increased, confirming the effectiveness of the stress protocol. Smooth muscle fibers of corpus cavernosum decreased from 14.07% (CG) to 8.98% (SG) (P = .02), and connective tissue increased from 53.66% (CG) to 64.47% (SG) (P = .01). Also, there was a higher level of type I collagen in the SG animals compared with the CG. Stress stimuli induced structural changes in the corpus cavernosum of rats suggestive of penile fibrosis, which may play a role in erection dysfunction.
Androgen receptor (AR) CAG(n) (polyglutamine) and GGN(n) (polyglycine) repeat polymorphisms determine part of the androgenic effect and may influence adiposity. The association of fat mass, and its regional distribution,...Androgen receptor (AR) CAG(n) (polyglutamine) and GGN(n) (polyglycine) repeat polymorphisms determine part of the androgenic effect and may influence adiposity. The association of fat mass, and its regional distribution, with the AR CAG(n) and GGN(n) polymorphisms was studied in 319 and 78 physically active nonsmoker men and women (mean ± SD: 28.3 ± 7.6 and 24.8 ± 6.2 years old, respectively). The length of CAG and GGN repeats was determined by polymerase chain reaction and fragment analysis, and confirmed by DNA sequencing of selected samples. Men were grouped as CAG short (CAG(S)) if harboring repeat lengths ≤ 21, the rest as CAG long (CAG(L)). The corresponding cutoff CAG number for women was 22. GGN was considered short (GGN(S)) if GGN ≤ 23, the rest as GGN long (GGN(L)). No association between AR polymorphisms and adiposity or the hormonal variables was observed in men. Neither was there a difference in the studied variables between men harboring CAG(L) + GGN(L),CAG(S) + GGN(S),CAG(S) + GGN(L), and CAG(L) + GGN(S) combinations. However, in women, GGN(n) was linearly related to the percentage of body fat (r = 0.30, P < .05), the percentage of fat in the trunk (r = 0.28, P < .05), serum leptin concentration (r = 0.40, P < .05), and serum osteocalcin concentration (r = 0.32, P < .05). In men, free testosterone was inversely associated with adiposity and serum leptin concentration, and positively with osteocalcin, even after accounting for differences in CAG(n), GGN(n), or both. In summary, this study shows that the AR repeat polymorphism has little influence on absolute and relative fat mass or its regional distribution in physically active men. In young women, GGN length is positively associated with adiposity, leptin, and osteocalcin.
Relaxin is a circulating hormone with functions in pregnancy, parturition, and other aspects of female reproduction. It is also secreted from the prostate gland into the seminal fluid; however, the role of relaxin in mal...Relaxin is a circulating hormone with functions in pregnancy, parturition, and other aspects of female reproduction. It is also secreted from the prostate gland into the seminal fluid; however, the role of relaxin in male reproduction is debated. Studies conducted in the past have suggested possible actions on human spermatozoa, but the data were contrasting. Here, we show that the relaxin receptor RXFP1 (Relaxin Family Peptide Receptor 1) is expressed in human spermatozoa, and it mainly localizes in the astrodome. In vitro studies on human sperm demonstrated that this hormone attenuates the natural decline in sperm motility and maintains higher mitochondrial activity and lower apoptosis level. Furthermore, relaxin induced an increase in sperm hyperactivation, intracellular calcium and cAMP, and acrosome reaction. These effects were abolished by the use of the specific anti-RXFP1 antibody. Relaxin concentrations were low in the blood (x ± SD, 0.16 ± 0.03 nM) and very high in the seminal plasma (x ± SD, 10.3 ± 4.0 nM), confirming its secretion mainly by the prostate. Taken together, these data demonstrate that relaxin influences positively many sperm functions linked to fertilizing ability, and it preserves sperm functionality, with possible practical value in assisted reproduction techniques.
The role of dihydrolipoamide dehydrogenase (DLD), the E3 subunit of the pyruvate dehydrogenase complex (PDHc) in hamster sperm capacitation and acrosome reaction has been implicated previously. In this study, attempt has...The role of dihydrolipoamide dehydrogenase (DLD), the E3 subunit of the pyruvate dehydrogenase complex (PDHc) in hamster sperm capacitation and acrosome reaction has been implicated previously. In this study, attempt has been made to understand DLD/PDHc involvement from the perspective of pyruvate/lactate metabolism. Inhibition of DLD was achieved by the use of a specific inhibitor, 5-methoxyindole-2-carboxylic acid. It was seen that 5-methoxyindole-2-carboxylic acid-treated spermatozoa with inhibited DLD (and PDHc) activity had lactate accumulation, which caused an initial lowering of the intracellular pH and calcium and an eventual block in capacitation and acrosome reaction. Collectively, the data reveal a significant contribution of the metabolic enzymes DLD and PDHc to lactate regulation in hamster spermatozoa during capacitation and acrosome reaction. Additionally, the importance of lactate regulation in the maintenance of sperm intracellular pH and calcium, two important physiologic factors essential for sperm capacitation and acrosome reaction, has also been established.
The relationship between sex steroids and osteoprotegerin (OPG) in patients with prostate cancer is not well established. Our aim was to evaluate serum OPG levels in patients with prostate cancer and its relationship wit...The relationship between sex steroids and osteoprotegerin (OPG) in patients with prostate cancer is not well established. Our aim was to evaluate serum OPG levels in patients with prostate cancer and its relationship with sex steroids, bone mineral density, bone turnover markers, and fractures. We performed a cross-sectional study including 91 patients with prostate cancer. We determined: bone mineral density by dual-energy x-ray absorptiometry, bone turnover markers, serum levels of sex steroids and osteoprotegerin, and prevalent radiographic vertebral fractures. Serum OPG levels were higher in patients with vertebral fractures (8.02 ± 2.0 vs 4.91 ± 0.28 pmol/L; P < .05). OPG level and the duration of hormonal therapy were related (r = 0.299, P = .004), but this association did not persist after adjustment for age. In patients without androgen deprivation therapy, serum OPG levels were correlated with the levels of total testosterone (r = 0.508, P = .001) and bioavailable testosterone (r = 0.311, P = .037). In patients receiving androgen deprivation therapy, serum OPG levels were correlated with levels of total estradiol (r = 0.199, P = .18), bioavailable estradiol (r = 0.37, P = .009), and free estradiol (r = 0.349, P = .016). In conclusion, in patients with prostate cancer treated with androgen deprivation therapy, serum OPG levels were correlated with the levels of total estradiol, bioavailable estradiol, and free estradiol. Our hypothesis is that in patients with androgen deprivation therapy, the higher relative estrogen levels could stimulate OPG production in response to the higher resorption state. Future prospective studies are needed to clarify the role of OPG in androgen deprivation therapy-mediated bone loss.
This prospective study evaluated the safety of tadalafil 5 mg taken once a day in terms of hypotensive side effects and whether it improves lower urinary tract symptoms (LUTS) and restores sexual function in patients wit...This prospective study evaluated the safety of tadalafil 5 mg taken once a day in terms of hypotensive side effects and whether it improves lower urinary tract symptoms (LUTS) and restores sexual function in patients with erectile dysfunction who are receiving concomitant α-blocker (AB) therapy for benign prostatic hyperplasia (BPH). A total of 158 LUTS/BPH patients receiving AB therapy for ≥3 months were given tadalafil 5 mg once a day. Before treatment with tadalafil (V1), and 4 weeks (V2) and 12 weeks (V3) after starting tadalafil, blood pressure, heart rate, International Prostate Symptom Score (IPSS), maximal urine flow rate (Qmax), postvoiding residual urine volume, and International Index of Erectile Function (IIEF-5) score were measured. Of the 158 LUTS/BPH patients, a total of 119 completed the trial. Blood pressure (systolic and diastolic) and heart rate did not change. IPSS and IIEF-5 scores improved significantly, but Qmax and postvoiding residual urine volume did not; however, in the 39 men with a low baseline Qmax (≤10 mL/s), Qmax rose significantly from 7.97 ± 1.44 mL/s (baseline) to 8.91 ± 1.60 mL/s (V3; P = .012). The remaining patients (baseline Qmax >10 mL/s) did not change. At V2 and V3, adverse side effects were observed in 10 men (7.30%) and 6 men (5.04%), respectively. Facial flushing was the most common adverse side effect (6 men at V2 and 4 men at V3), followed by headache (2 men each at V2 and V3) and dizziness (2 men at V2). Two patients dropped out of the study because of adverse side effects. In conclusion, tadalafil 5 mg once a day in combination with AB appeared to have few adverse effects on hypotensive events and can improve LUTS and restore sexual function.
A prospective randomized controlled study was designed to evaluate the effects of recombinant human follicle-stimulating hormone (rFSH) treatment on sperm DNA fragmentation in men with idiopathic oligoasthenoteratozoospe...A prospective randomized controlled study was designed to evaluate the effects of recombinant human follicle-stimulating hormone (rFSH) treatment on sperm DNA fragmentation in men with idiopathic oligoasthenoteratozoospermia (iOAT). One hundred twenty-nine men with sperm count less than 10 × 10(6) spermatozoa/mL and forward motility <25% were included; normal serum levels of FSH, luteinizing hormone (LH), and testosterone, and no other causes of infertility were enrolled. The patients were randomized into 2 groups: 65 men were treated on alternate days for 90 days with injections of 150 IU rFSH, and 64 subjects received nonantioxidant vitamin supplements. Main outcome measures were serum levels of FSH, LH, testosterone, and inhibin B and DNA fragmentation index (DFI) at baseline and after 90 days. No significant differences were observed between the 2 groups with regard to sperm parameters and hormone values. The DFI was similar between the 2 groups at the time of the enrollment but reduced significantly (P < .05) after rFSH therapy in study group, whereas no significant variation occurred in the control group. In the subgroup of patients with high basal DFI values (>15%), rFSH treatment significantly increased DFI (P < .01), whereas no significant variation occurred after 90 days of vitamin supplements. We conclude that rFSH administration improves sperm DNA integrity in iOAT men with increased DFI values. The degree of sperm DFI might be useful to identify those iOAT patients in which rFSH treatment can be advantageous.
The effect of transurethral procedures for benign prostate hyperplasia (BPH) on male sexual function is still controversial, and we conducted this meta-analysis to compare the effects of different transurethral surgical...The effect of transurethral procedures for benign prostate hyperplasia (BPH) on male sexual function is still controversial, and we conducted this meta-analysis to compare the effects of different transurethral surgical procedures for the treatment of symptomatic BPH on male erectile function (EF) and ejaculatory function (EJF). Databases, including MEDLINE, EMBASE, and the Cochrane Controlled Trial Register, were searched to identify randomized controlled trials (RCT) that compared watchful waiting, transurethral electrovaporization (TUEVP) or holmium laser treatment (HLT) with transurethral resection of the prostate (TURP). Trials were included if they were RCTs, contained fully available data, compared with conventional TURP for BPH, and referred to male EF and EJF. A total of 12 RCTs involving a total of 1889 subjects were selected for analysis, including 2 trials comparing TURP and watchful waiting, 6 comparing TURP with TUEVP, and 4 comparing TURP with HLT. TURP was associated with a higher occurrence of retrograde ejaculation compared with watchful waiting but not to TUEVP (P = .95) or HLT (P = .37) and associated with a lower incidence of male erectile dysfunction compared with TUEVP (P = .04) but not HLT. According to the analysis, TURP lead to a higher prevalence of retrograde ejaculation compared with watchful waiting but had less of an effect on EF than TUEVP. TURP did not have a significantly different effect on EF or EJF compared with HLT.
Our objectives were to evaluate the effects of mono(2-ethylhexyl) phthalate (MEHP) on tight junctions (TJ) in cultured rat Sertoli cells (SC) and to investigate changes in the signal transduction pathways in SCs followin...Our objectives were to evaluate the effects of mono(2-ethylhexyl) phthalate (MEHP) on tight junctions (TJ) in cultured rat Sertoli cells (SC) and to investigate changes in the signal transduction pathways in SCs following MEHP treatment. SCs were isolated and purified from the testes of 18-day-old Sprague Dawley rats and incubated at 34°C for 3 days. After treatment of SCs with either the vehicle or MEHP for 0.5, 1, 3, 6 and 24 hours, whole cell lysates were isolated from each replicate to prepare RNA and protein. Expression levels of claudin-11, occludin, and zonula occludens-1 (ZO-1) mRNA were evaluated by quantitative real-time reverse transcription-polymerase chain reaction and changes in signal transduction pathways possibly induced by MEHP treatment were assessed by Western blot analyses. MEHP treatment led to significant decreases in the expression of claudin-11 and occludin mRNA, but not that of ZO-1, in rat SCs. Exposure of rat SCs to MEHP resulted in the marked induction of phosphorylated p44/42 mitogen-activated protein kinase (MAPK), whereas other pathways examined in this study were not activated by MEHP. Furthermore, treatment of rat SCs with a specific inhibitor of p44/42 MAPK prevented the MEHP-induced down-regulation of claudin-11 and occludin. These findings demonstrate that MEHP exposure inhibited the expression of claudin-11 and occludin mRNA in rat SCs through the p44/42 MAPK pathway, suggesting the possible involvement of MEHP in spermatogenic function by regulating major components of TJs in SCs.
Phthalate esters are commonly used plasticizers found in many household items, personal care products, and medical devices. Animal studies have shown that in utero exposure to di-(n-butyl) phthalate (DBP) within a critic...Phthalate esters are commonly used plasticizers found in many household items, personal care products, and medical devices. Animal studies have shown that in utero exposure to di-(n-butyl) phthalate (DBP) within a critical window during gestation causes male reproductive tract abnormalities resembling testicular dysgenesis syndrome. Our studies utilized p53-deficient mice for their ability to display greater resistance to apoptosis during development. This model was chosen to determine whether multinucleated germ cells (MNG) induced by gestational DBP exposure could survive postnatally and evolve into testicular germ cell cancer. Pregnant dams were exposed to DBP (500 mg/kg/day) by oral gavage from gestational day 12 until birth. Perinatal effects were assessed on gestational day 19 and postnatal days 1, 4, 7, and 10 for the number of MNGs present in control and DBP-treated p53-heterozygous and null animals. As expected, DBP exposure induced MNGs, with greater numbers found in p53-null mice. Additionally, there was a time-dependent decrease in the incidence of MNGs during the early postnatal period. Histologic examination of adult mice exposed in utero to DBP revealed persistence of abnormal germ cells only in DBP-treated p53-null mice, not in p53-heterozygous or wild-type mice. Immunohistochemical staining of perinatal MNGs and adult abnormal germ cells was negative for both octamer-binding protein 3/4 and placental alkaline phosphatase. This unique model identified a role for p53 in the perinatal apoptosis of DBP-induced MNGs and provided insight into the long-term effects of gestational DBP exposure within a p53-null environment.