Long-term follow-up results of testicular torsion in children.

A retrospective cohort study was conducted at the Children's Hospital of Chongqing Medical University from November 2004 to December 2020 to investigate the long-term follow-up results after testicular torsion (TT) in children. Boys with TT were divided into the salvage orchiopexy group and the orchiectomy group, and the baseline characteristics, ultrasonographic indications, intraoperative findings, testicular volumes, and adverse events during follow-up were compared. A total of 145 cases were included in this study. Approximately 56.6% of patients who underwent salvage orchiopexy had testicular atrophy (TA), and the median testicular volume loss of the testes was 57.4%. Age less than 6 years, delayed surgery, and intraoperative poor blood supply were associated with TA in pediatric TT after orchiopexy. Most atrophied testes appeared within 3-6 months after surgery. Compared with the corresponding age-matched healthy controls, the contralateral testicular volumes were larger in the orchiopexy (P = 0.001 without TA, and P = 0.042 with TA) and orchiectomy groups (P = 0.033). The adverse events were comparable in patients with orchiectomy or orchiopexy. In summary, follow-up before 3 months after surgery may not offer sufficient clinical value, while that 3 months after surgery should be regarded as the first follow-up time for testicular monitoring. The contralateral testes of patients with TT showed compensatory hypertrophy. We suggest performing orchiectomy when torsed testes are surgically assessed as Arda grade III or inviable.

Diagnosis, treatment, outcome, and reasons for delayed treatment of cryptorchidism with torsion in children: a 16-year retrospective study in a large pediatric medical center.

We describe and summarize the diagnosis, treatment, and reasons for delayed treatment of children with cryptorchidism torsion in Children's Hospital of Chongqing Medical University. The study included 19 cases of cryptorchidism torsion. The age of the children ranged from 16 days to 12 years (median: 6 years). The interval from diagnosis to surgery varied from 4 h to 16 days (median: 3 days). Ultrasound was performed in all cases. Fifteen cases had cryptorchidism torsion, 2 cases had a soft tissue mass in the inguinal region, and 2 cases had an inguinal/abdominal teratoma. Five cases were treated with an orchidopexy, 12 cases were treated with orchiectomy, and 2 cases received resection of a testicular tumor. The 5 children with an orchidopexy were followed up from 1 month to 7 years (median: 3 years), with 1 child having a testis retraction and no blood supply. Of the 12 children who had an orchiectomy, three had delayed diagnosis due to family unawareness of the condition, while other delays were due to delayed referral from primary care facilities. The relative rarity and insufficient awareness of cryptorchidism torsion resulted in a low rate of testicular salvage. Therefore, hospitals of all levels should be fully aware of cryptorchidism with torsion and ensure a male child's genital system and inguinal region are examined to improve the success rate of testicular salvage.

The impact of the COVID-19 pandemic on pediatric operations: a retrospective study of Chinese children.

BACKGROUND: The aim of this study was to quantify the impact of coronavirus disease 2019 (COVID-19) on pediatric operations, and establish preoperative, intraoperative, and postoperative protocols to improve the pediatric operations. METHODS: We here compare the number of patients who underwent surgery in Chongqing Medical University Affiliated Children's Hospital during the pandemic (January 23-March 11), after the pandemic (March 12-April 30), after our measures were put in place (May 1-May 21), and the equivalent period in 2019. RESULT: During the COVID-19 pandemic, 62.68% fewer patients underwent surgery than during the homologous period of time 1 year earlier (P < 0.01). After the COVID-19 pandemic, the number of orchidopexy cases increased significantly from 175.14 to 504.57 per week (P < 0.01). The large number of patients that accrued in our hospital may have increased the risk of COVID-19 transmission. In response, hospitals and clinics have made protocols and reorganized healthcare facilities (e.g., performing nucleic acid tests (NAT), adding adequate personal protective equipment (PPE)) from May 1, 2020. After the measures were implemented, the number of operations performed remained stable and comparable to the pre-pandemic period. COVID-19 RNA detection was performed in 5104 cases and there were no new confirmed cases in our hospital. CONCLUSION: This outbreak of COVID-19 has affected not only individuals with COVID-19 but also patients seeking surgical operations. Understanding the present situation helps clinicians provide a high level of treatment to all children.

The gut-microbiota-testis axis mediated by the activation of the Nrf2 antioxidant pathway is related to prepuberal steroidogenesis disorders induced by di-(2-ethylhexyl) phthalate.

Di-(2-ethylhexyl) phthalate (DEHP) is a common plasticizer, which is known to be an environmental endocrine-disrupting chemical that can jeopardize the male reproductive system. Prepuberal exposure to DEHP leads to steroidogenesis disorders. However, the specific mechanism remains ambiguous. Therefore, Sprague Dawley (SD) rats underwent prepuberal DEHP exposure at a dose of 500 mg/kg per day through gavage. Additionally, the resulting testicular injury was evaluated to confirm the disturbed steroidogenesis. Changes in testicular histology, significant reduction of serum testosterone (P < 0.01) and luteinizing hormone (P < 0.001), and significantly decreased expressions of steroidogenic acute regulatory protein (P < 0.01) and 3-beta-hydroxysteroid dehydrogenase (P < 0.05) were found in DEHP-treated rats. DEHP exposure resulted in obvious intestinal damage and oxidative stress imbalance, primarily in the jejunum. Both the activation of the nuclear factor-E2-related factor 2 (Nrf2) signaling pathway and alterations of microbiota profiles were observed in all three gut specimens, but were most notable in the jejunum. We hypothesize that the gut-microbiota-testis axis, which is mediated by the activation of the Nrf2 antioxidant pathway, could be involved in the dysfunction of prepuberal steroidogenesis induced by DEHP.

Increased m6A RNA modification is related to the inhibition of the Nrf2-mediated antioxidant response in di-(2-ethylhexyl) phthalate-induced prepubertal testicular injury.

Di-(2-ethylhexyl) phthalate (DEHP) is a common environmental endocrine disrupting chemical that may induce male reproductive disorders. Exposure to DEHP at a prepubertal stage could lead to prepubertal testicular injury, but the underlying mechanisms remain unclear. In this study, we exposed Sprague-Dawley rats to 0, 250, and 500 mg DEHP per kg body weight per day at the prepuberty stage from postnatal day 22 (PND 22) to PND 35 by oral gavage. Testicular injury and oxidative stress were evaluated, and the levels of 6-methyladenosine (m6A) modification and expression of modulator genes for RNA methylation were measured in testes. Furthermore, m6A modification of the important antioxidant transcription factor Nrf2 was analyzed using methylated RNA immunoprecipitation qPCR. Our results show that DEHP worsened testicular histology, decreased testosterone concentrations, downregulated expression of spermatogenesis inducers, enhanced oxidative stress, inhibited the Nrf2-mediated antioxidant pathway, and increased apoptosis in testes. Additionally, DEHP increased global levels of m6A RNA modification and altered the expression of two important RNA methylation modulator genes, FTO and YTHDC2. Moreover, m6A modification of Nrf2 mRNA increased upon DEHP exposure. Overall, these findings link oxidative stress imbalance with epigenetic effects of DEHP toxicity and provide insight into the testicular toxicity of DEHP from the new perspective of m6A modification.

Incidence characteristics of testicular microlithiasis and its association with risk of primary testicular tumors in children: a systematic review and meta-analysis.

BACKGROUND: To systematically evaluate the incidence characteristics of testicular microlithiasis (TM) in children and its association with primary testicular tumors (PTT). METHODS: A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. A priori protocol was registered in the PROSPERO database (CRD42018111119), and a literature search of all relevant studies published until February 2019 was performed. Prospective, retrospective cohort, or cross-sectional studies containing ultrasonography (US) data on the incidence of TM or the association between TM and PTT were eligible for inclusion. RESULTS: Of the 102 identified articles, 18 studies involving 58,195 children were included in the final analysis. The overall incidence of TM in children with additional risk factors for PTT was 2.7%. In children, the proportion of left TM in unilateral cases was 55.7%, the frequency of bilateral TM was 69.0%, and proportion of classic TM was 71.8% [95% confidence interval (CI) 62.4-81.1%, P = 0.0, I2 = 0.0%]. About 93.5% of TM remained unchanged, and newly detected PTT rate was very low (4/296) during follow-up. The overall risk ratio of TM in children with a concurrent diagnosis of PTT was 15.46 (95% CI 6.93-34.47, P < 0.00001). CONCLUSIONS: The incidence of TM in children is highly variable. Nonetheless, TM is usually bilateral, of the classic type, and remains stable or unchanged at follow-up. Pediatric patients with TM and contributing factors for PTT have an increased risk for PTT; however, there is no evidence to support mandatory US surveillance of children with TM.

Automobile exhaust-derived PM2.5 induces blood-testis barrier damage through ROS-MAPK-Nrf2 pathway in sertoli cells of rats.

Particulate matter with an aerodynamic diameter of less than 2.5 µm (PM2.5) derived from automobile exhaust can lead to serious male spermatogenesis dysfunction, but its specific molecular mechanism is unclear. In this experiment, we focused on the blood-testis barriers (BTB) and explored the intracellular mechanisms underlying the fertility toxicity of PM2.5 originating from automobile exhaust in the primary cultured Sertoli cells(SCs) of rats. After PM2.5 exposure, excessive reactive oxygen species (ROS) and increased apoptosis of SCs were detected. The expression of the BTB related proteins including ZO-1, Occludin, N-cadherin and ß-catenin were significantly decreased and the spatial arrangement of F-actin was completely disordered through Immunofluorescence and Western blots tests. The phosphorylation of Jun N-terminal kinase (JNK), extracellular signal regulatory kinase (ERK), p38 mitogen-activated protein kinase (MAPK) were upregulated and nuclear factor (erythroid-derived 2) -like 2-related factor (Nrf2) was downregulated respectively. However, combined utilization of vitamin C and E were observed to prevent the increase of ROS generation, reduce celluar apoptosis, increase the expression of BTB related proteins, reconstructed the spatial arrangement of F-actin as well as improved the Nrf2 expression and attenuated the phosphorylation of the MAPK kinases and cleaved caspase-3 levels. Furthermore, ERK inhibitor (SCH772984), JNK inhibitor (SP600125) and p38 MAPK inhibitor (SB203580) obviously up-regulated BTB-related proteins expression as well as activated Nrf2 expression at varying degrees, indicating that ROS-MAPKs-Nrf2 is involved in the signaling pathway that leads to PM2.5-induced spermatogenesis dysfunction. These findings indicate that PM2.5 derived from automobile exhaust causes oxidative stress, which in turn causes cellular apoptosis of SCs and damage of the blood-testis barrier, resulting male spermatogenesis dysfunction, in which ROS-MAPK-Nrf-2 pathways may play a key role.

Clinical and socioeconomic factors associated with delayed orchidopexy in cryptorchid boys in China: a retrospective study of 2423 cases.

We investigated the associations of clinical and socioeconomic factors with delayed orchidopexy for cryptorchidism in China. A retrospective study was conducted on cryptorchid boys who underwent orchidopexy at Children's Hospital at Chongqing Medical University in China from January 2012 to December 2017. Of 2423 patients, 410 (16.9%) received timely repair by 18 months of age, beyond which surgery was considered delayed. Univariate analysis suggested that the laterality of cryptorchidism (P = 0.001), comorbidities including inguinal hernia/scrotal hydrocele (P < 0.001) or urinary tract disease (P = 0.016), and whether patients lived in a poverty county (P < 0.001) could influence whether orchidopexy was timely or delayed. Logistic regression analysis suggested that the following factors were associated with delayed repair: unilateral rather than bilateral cryptorchidism (odds ratio [OR] = 1.752, P < 0.001), absence of inguinal hernia or hydrocele (OR = 2.027, P = 0.019), absence of urinary tract disease (OR = 3.712, P < 0.001), and living in a poverty county (OR = 2.005, P < 0.001). The duration of postoperative hospital stay and hospital costs increased with the patient's age at the time of surgery.

Spermatogenesis dysfunction induced by PM2.5 from automobile exhaust via the ROS-mediated MAPK signaling pathway.

Long-term exposure to particulate matter 2.5 (PM2.5) from automobile exhaust impairs spermatogenesis through oxidative stress injury, but the underlying mechanism is unknown. To investigate the toxic mechanism of PM2.5-induced spermatogenesis impairment, we focused on the MAPK signaling pathway. We also examined the effects of treatment with vitamins C and E on spermatogenic function. Male SD rats were divided randomly into three groups: control (0.9% sterilized saline), PM2.5 exposure (20 mg/kg.b.w.), and PM2.5 exposure (20 mg/kg.b.w.) with vitamin intervention (vitamin C, 100 mg/kg.b.w.; vitamin E, 50 mg/kg.b.w.). Male rats showed a marked decline in fertility and decreased sperm quality after PM2.5 exposure. The expression of SOD and Nrf2 was significantly decreased, and that of MDA was increased markedly. The expression of blood-testis barrier-associated proteins, such as ZO-1, occludin, connexin 43, and ß-catenin, was significantly decreased, the Bcl-2/Bax ratio was downregulated, and the cleaved caspase-3 level was increased. Phosphorylation of MAPKs, including ERKs, JNKs, and p38, was upregulated. Treatment with vitamins C and E reversed the damage induced by PM2.5 exposure. These results suggest that PM2.5 from automobile exhaust disrupted spermatogenesis via ROS-mediated MAPK pathways, and that a combined vitamin C and E intervention effectively mitigated toxicity in the male reproductive system.

Testicular developmental impairment caused by flutamide-induced and DEHP-induced cryptorchid rat models is mediated by excessive apoptosis and deficient autophagy.

BACKGROUND: Cryptorchidism is a common condition of childhood, and it is known to impair fertility potential. However, the underlying mechanisms remain unclear. METHODS: This study constructed two cryptorchid rat models to investigate the roles of apoptosis and autophagy in testicular impairment induced by cryptorchidism. Pregnant rats were randomly divided into three groups. Group I: non-treated rats were used as controls. Group II: injected with drug Flutamide (Flu) 25 mg/kg/bw/d from gestation day (GD) 11-19. Group III: daily intragastric administration of 750 mg/kg/bw/d di-2-ethylhexylphosphate (DEHP) from GD 7-19. The cubs were feed normally and the testes were excised on postnatal day (PND) 30. RESULTS: Our results demonstrated cryptorchidism models induced noticeable decreased fertility, significantly reduced sperm count, increased sperm abnormality rate, decreased testosterone and severe testicular damage in histomorphology. Intriguingly, the level of apoptosis marker FAS, Cytochrome C and caspase-3 increased in Flu-induced and DEHP-induced groups. DEHP-induced treatment simultaneously increased the number of autophagosomes and the levels of autophagy marker LC3-II and p62. Significant decrease of autophagy gene (LC3-II and p62) expression is found in Flu-induced rats testes. CONCLUSION: Taken together, deficient autophagy is involved in testicular spermatogenesis damage of cryptorchidism rats. And this autophagy defect is caused by deficient degradation.

Urban fine particulate matter (PM2.5) exposure destroys blood-testis barrier (BTB) integrity through excessive ROS-mediated autophagy.

CONTEXT: Blood-testis barrier (BTB), constituted by tight junctions (TJs), adherens junctions and gap junctions, is important for spermatogenesis. PM2.5 is known to impair testicular functions and reproduction. However, its effects on BTB and the underlying mechanisms remain obscure. OBJECTIVE: To investigate the roles of autophagy in BTB toxicity induced by PM2.5. MATERIALS AND METHODS: Sprague-Dawley rats were developmentally exposed to normal saline (NS) or PM2.5 with the doses of 9 mg/kg b.w. and 24 mg/kg b.w. via intratracheal instillation for seven weeks. Success rate of mating, sperm quality, testicular morphology, expressions of BTB junction proteins and autophagy-related proteins were detected. In addition, expressions of oxidative stress markers were also analyzed. RESULTS: Our results demonstrated that developmental PM2.5 exposure induced noticeable decreased fertility, significantly reduced sperm count, increased sperm abnormality rate and severe testicular damage in histomorphology. The expressions of TJ (such as ZO-1 and occludin), gap junction (such as connexin43) were down-regulated significantly after PM2.5 treatment. Intriguingly, PM2.5 simultaneously increased the number of autophagosomes and the levels of autophagy marker LC3-II and p62, suggesting that the accumulated autophagosomes resulted from impaired autophagy degradation. Moreover, the expressions of HO-1 levels remarkably increased and expression levels of Gpx and SOD were significantly decreased after PM2.5 exposure. Vitamins E and C could alleviate the PM2.5-induced oxidative stress, reverse the autophagy defect and restore the BTB impairment. CONCLUSIONS: Taken together, the results suggest that PM2.5 exposure destroys BTB integrity through excessive ROS-mediated autophagy. Our finding could contribute to a better understanding of PM2.5-induced male reproductive toxicity.

Diagnosis and treatment of urethral prolapse in children: 16 years' experience with 89 Chinese girls.

OBJECTIVE: To review our experience and results in the diagnosis and treatment of urethral prolapse (UP) in Chinese girls. PATIENTS AND METHODS: We conducted a retrospective chart review of 89 consecutive girls (aged <16 years) with UP and without other complications, who received treatment for UP from January 1999 to January 2015 (a study period of 16 years) at the Children's Hospital of Chongqing Medical University, China. Data analysed included: age, symptoms, clinical findings, predisposing factors, management, and outcomes. RESULTS: The presenting symptoms in the 89 girls were: mass (54 girls), bleeding (34), and dysuria/straining at micturition (one). In all, 14 patients received conservative treatment as their symptoms were mild, and 75 were successfully treated by excision of the prolapsed urethral mucosa or ligation over a Foley catheter, as their symptoms were severe and recurred too frequently to be managed conservatively. The mean postoperative length of stay for ligation was 7.76 days and for excision was 4.57 days. Ligation over a Foley catheter had a longer hospital stay. CONCLUSIONS: UP is a rare condition occurring in prepubertal girls, evidenced by a urethral mass and bleeding. Increased physician awareness and early recognition of UP avoids unnecessary examinations and patient anxiety.

Urban fine particulate matter exposure causes male reproductive injury through destroying blood-testis barrier (BTB) integrity.

Blood-testis barrier (BTB) provides a suitable microenvironment for germ cells that is required for spermatogenesis. Exposure to particulate matter (PM) is recognized to occasion male reproductive impairment, but the mechanism of which remains unclear. Male Sprague-Dawley (SD) rats were used to establish animal models with PM2.5 exposure concentration of 0, 10, and 20mg/kg.b.w. once a day for four weeks. Success rate of mating, sperm quality, epididymal morphology, expressions of spermatogenesis markers, superoxide dismutases (SOD) activity and expression in testicular tissues, and expressions of BTB junction proteins were detected. In addition, in vitro experiments were also performed. After PM2.5 treatment, reactive oxygen species (ROS) production and apoptosis of Sertoli cells were analyzed. Our results indicated that after PM2.5 exposure male rats presented inferior uberty and sperm quality, with decreased expressions of spermatogenesis markers, escalated SOD activity and expression levels, and reduced expressions of tight junction, adherens junction, and gap junction proteins in testicular tissues. Meantime, PM2.5-treated Sertoli cells displayed increased SOD production and apoptosis. PM2.5 exposure engenders male reproductive function injury through breaking BTB integrity.

A 22-year retrospective study: educational update and new referral pattern of age at orchidopexy.

OBJECTIVES: To determine the current age at orchidopexy in China and whether changing targets have altered practice, as research suggesting progressive deterioration in an undescended testis (UDT) has led to the reduction in the target age for orchidopexy to 6-12 months but it is still unknown whether changing targets have altered practice. PATIENTS AND METHODS: The demographics of orchidopexies performed in the Children's Hospital of Chongqing Medical University between 1993 and 2014 were reviewed. A survey of the general publics' awareness of UDT and survey of primary healthcare practitioners' current opinion on age at orchidopexy and referral patterns were performed. RESULTS: In all, 3784 orchidopexies were performed over 22 years. The median age at orchidopexy fell between 1993 and 2014. There was an initial drop in the median age for orchidopexy between 2000 and 2010 (36 months) compared with 1993 and 2000 (48 months) (P < 0.05); however, beyond the corresponding target age (<18 months). The age for orchidopexy between 2010 and 2014 was also beyond the corresponding target age (6-9 months). The survey of the general public showed that 0.98% had knowledge of UDT and none of them knew about the target age for orchidopexy in the survey of 5393 cases. In all, 63.46% of them were told about the UDT by healthcare practitioners at the 1-4 months postnatal baby check. Furthermore, only 2% of the healthcare practitioners knew the recommended age for orchidopexy was 6-9 months and only 14.3% of them would directly make a surgical referral to paediatric surgery specifically at this point. CONCLUSIONS: The recommended orchidopexy age is not being achieved and we recognise the national need to address this. The approach should include the right cognition of cryptorchidism among the general public and earlier primary care referral directly from the routine postnatal baby check to a specialist centre prepared to undertake surgery in this age group.

[Testicular teratoma in children: Analysis of 64 cases].

OBJECTIVE: To improve the diagnosis and treatment of testicular teratoma in children by analysis of clinical data. METHODS: We retrospectively analyzed the clinical data about 64 cases of testicular teratoma treated in the Children's Hospital of Chongqing Medical University from 1995 to 2014. RESULTS: Sixty-one of the cases presented painless scrotal mass with a sense of bearing down and the other 3 cases were confirmed because of empty scrotum diagnosed as cryptorchidism. The level of serum alpha fetal protein ( AFP) was obviously increased in 46 cases but normal in the other 18 preoperatively. Ultrasonography manifested abnormal inhomogeneous echo zones with calcification or necrosis. X-ray examination presented patchy or curvilinear high-density shadows in 28 cases. Forty-one of the patients underwent testis-sparing surgery (TSS) , 20 received high inguinal orchiectomy, and 3 refused surgical treatment. Pathological examination revealed 3 mature germinal layers in the 49 cases of mature teratoma and immature germinal tissue, including the original neural tube, and 11 cases of immature teratoma. The mature cases were exempted from chemotherapy, while the immature cases received the combination of cisplatin, etoposide, and bleomycin (PEB). The patients were followed up for 2 years postoperatively, which revealed no recurrence or metastasis. CONCLUSION: Most children with testicular teratoma presented painless scrotal mass with a sense of bearing down and with abnormal serum AFP in most cases. Ultrasonography and plain radiography of the scrotum contribute to the diagnosis of the tumor. TSS is the main treatment option and intraoperative frozen-section can help the surgeons decide on the surgical mode. Postoperative chemotherapy is necessitated for immature teratoma but not for mature cases.

Transforming growth factor-beta3 expression up-regulates on cleft palates induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been shown to induce cleft palate, in which the molecular etiology of the defect is poorly characterized. Recently, transforming growth factor-beta3 (TGF-beta3) has been indicated to play an essential role in the development of palatal shelves. In this developmental toxicity study, we investigated the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the expression of TGF-beta3 in fetal mice. Pregnant C57BL/6 mice were exposed to corn oil or TCDD (32 microg/kg/day 64 microg/kg/day, per os) at embryonic day 10 (ED10), a drastic inhibition of palatal shelves was induced. By using RT-PCR (reverse transcription-polymerase chain reaction) and Western blot, the expressions of TGF-beta3 was investigated. We found that the expression of TGF-beta3 was gradually up-regulated in TCDD-treated group. These results suggest that cleft palate can be induced by TCDD exposure, the modification of TGF-beta3 is related to its pathogenesis.

[Effects of Di (2-ethylhexyl) phthalate on the testis and testicular gubernaculum of fetal KM mice].

OBJECTIVE: To explore the effects of Di (2-ethylhexyl) phthalate (DEHP) on the testis and testicular gubernaculum of fetal KM mice in vivo and to investigate the mechanism of DEHP-induced cryptorchidism. METHODS: Thirty healthy pregnant KM mice were randomly and equally divided into a blank control group, a corn oil control group and a DEHP group. The pregnant mice in the latter group were exposed to DEHP by gavage at the dose of 500 mg/kg body weight per day from gestation day 12 (GD12) through gestation day 19 (GD19). The effects of DEHP were observed on the number of fetuses per pregnancy, the ratio of male to female pups, the weight of the testis, the morphology and location of the testis and gubernaculum, the relative testis-bladder neck distance (TBD) and cranial suspensory ligament (CSL) residual. The expressions of the androgen receptor (AR), estrogen receptor (ER) and actin and proliferating cell nuclear antigen (PCNA) in the gubernaculum were detected by immunohistochemistry. RESULTS: DEHP reduced the testis weight and TBD, induced different degrees of testis maldescent, but produced no obvious effect on the body weight, the number of fetuses per pregnancy, the sex ratio and the testis gubernacular morphology. Under the light microscope, hypotrophy was seen in all the testis seminiferous tubules, spermatogenic cells and Sertoli cells, marked Leydig cell hyperplasia was noted, and the positive expression of AR in the gubernaculum was decreased in the DEHP group (P < 0.01). CONCLUSION: DEHP could cause dysfunction of the testis gubernaculum via its anti-androgen effect, induce cryptorchidism, and cause dysplasia and dysfunction of Sertoli cells, Leydig cells and spermatogenic cells in fetal mice.

[Di-(2-ethylhexyl) phthalate increases the DNA methylation level of genomes in the mouse testis].

OBJECTIVE: To investigate the effect of the exposure to di- (2-ethylhexyl) phthalate (DEHP) during pregnancy on the DNA methylation level of genomes in the testis of the offspring in mice. METHODS: Pregnant KM mice were randomly divided into three groups, normal control, corn oil and DEHP-exposed. Corn oil and DEHP (500 mg/[kg x d]) were administrated respectively from gestation day 12.5 (GD 12.5) to postnatal day 3 (PND 3). The testes of the offspring were excised on PND 7, and their genomic DNA was treated with EcoR I /Msp I and EcoR I /Hpa II. The genome-wide DNA methylation patterns of the CCGG sites were detected by methylation-sensitive amplification polymorphism (MSAP). The samples were electrophoresed in the ABI 3730 DNA sequencer and the results analyzed by the Genescan3.1. RESULTS: The average incidence of DNA methylation was (34.03 +/- 3.05)% in the DEHP-exposed mice, obviously higher than (28.37 +/- 2.37)% in the normal control and (28.58 2.45)% in the corn oil group, with statistically significant differences (P < 0.05). CONCLUSION: Exposure to DEHP during pregnancy increases the DNA methylation level of the genome in the testis of the offspring and affects the apparent genetic modification of the genome, which may be one of the important toxicological causes of the lesion in the reproductive system.