Association of Maternal First Trimester Serum Levels of Free Beta Human Chorionic Gonadotropin and Hypospadias: A Population Based Study.

PURPOSE: Human chorionic gonadotropin stimulates fetal testosterone production and contributes to normal development of male genitalia. Using population based data we hypothesized that differences in maternal free beta human chorionic gonadotropin may be associated with hypospadias. MATERIALS AND METHODS: Data were obtained from the Paris Registry of Congenital Malformations (REMAPAR) (2011 to 2016). The initial study population included 3,172 pregnant women who gave birth to a singleton live born male infant with a congenital malformation. After exclusion of cases with unknown beta human chorionic gonadotropin and those with chromosomal or genetic abnormalities, the study population included 194 boys with isolated hypospadias and 1,075 controls. For cases with operative notes (125) we obtained data on type (proximal/distal) of hypospadias. Using quantile regression we compared median values of multiple of median beta human chorionic gonadotropin measured for first trimester Down syndrome screening (10th to 13th gestational weeks) for overall as well as by type of hypospadias vs controls. We also considered possible effects of placental dysfunction (maternal age, intrauterine growth retardation and preterm births) as potential confounding factors. RESULTS: Overall the median beta human chorionic gonadotropin multiple of median was comparable for women who had an infant with hypospadias vs controls (0.99 vs 0.95, p=0.3). However, proximal hypospadias was associated with a statistically significant higher median multiple of median than distal hypospadias or unspecified (1.49 vs 0.92 vs 1.05, p=0.02). The estimates were comparable after adjustment for placental dysfunction. CONCLUSIONS: Our findings support the hypothesis that an alteration in maternal beta human chorionic gonadotropin levels is associated with hypospadias. However, this association appears to be limited to proximal hypospadias.

Risk factors affecting post-pubertal high serum follicle-stimulating hormone in patients with hypospadias.

PURPOSE: The factors affecting spermatogenesis in adulthood in patients with hypospadias (HS) are not clearly understood. In the present study, risk factors affecting post-pubertal high serum follicle-stimulating hormone (FSH) were evaluated in patients with HS. MATERIALS AND METHODS: Among those with a history of HS surgery, patients in whom endocrinological evaluation regarding pituitary-gonadal axis was performed at 15 years of age or older between March 2004 and April 2018 were enrolled in the present study. High serum FSH was defined as greater than 10 mIU/ml. The severity of HS was divided into mild and severe. Factors affecting the post-pubertal high serum FSH were estimated. RESULTS: Seventy-nine patients were included in the present study. The severity of HS was mild in 35 and severe in 44. History of undescended testis (UDT) was confirmed in 12. High serum FSH was detected in nine. On logistic regression model analysis, a history of UDT was the only significant factor for high serum FSH. The incidence of high serum FSH in patients with UDT was significantly higher than that in those without UDT (58.3% vs 7.5%, p < 0.01). When stratified by severity of HS and the presence of UDT, high serum FSH was detected in 70% in patients with severe HS and UDT, whereas less than 10% in other groups. CONCLUSIONS: A history of UDT was a significant factor for post-pubertal high serum FSH in patients with HS. Accordingly, the presence of UDT may be a marker for impaired spermatogenesis in patients with HS, especially in severe cases.

Effects of pre- and post-pubertal dihydrotestosterone treatment on penile length in 5α-reductase type 2 deficiency.

Steroid 5α-reductase type 2 deficiency (5αRD2) is a congenital disorder of sex development caused by impairment of conversion from testosterone (T) to 5α-dihydrotestosterone (DHT). DHT deficiency leads to various degrees of undervirilized external genitalia including micropenis, primarily correlated with mutations of the SRD5A2 gene that encodes 5α-reductase type 2. Four Japanese boys with isolated micropenis were diagnosed as 5αRD2 by elevated ratios of serum T/DHT, and decreased ratios of urinary 5α/5ß-reduced steroid metabolites. Genetic analyses for SRD5A2 identified that the four patients shared a hypomorphic mutation R227Q that has a residual activity related to the mild-form of 5αRD2. For prepubertal micropenis, DHT was transdermally applied to the four patients at the ages of 4-11 year, increasing a median of stretched penile lengths (SPLs) from 2.6 cm (-2.5 SD) to 4.4 cm (-0.2 SD). Nevertheless, the post-pubertal penile growth was apparently retarded, despite normal levels of T secreted from well-developed testes. The second course of DHT treatment underwent at ages of 12-18 year, but unable to normalize SPLs at a range of 6.0 to 7.0 cm (-3.4 to -2.4 SD). The prostate volumes of two patients were variable at 8.1 and 21 cm3, and a sperm cell count of one patient was normal as young adult. DHT treatment contributes to development of the penis and prostate, which are favorable for the potential fertility of 5αRD2 adults. Meanwhile, the retarded penile growth and a risk of prostate overgrowth may complicate the post-pubertal management with DHT for 5αRD2 males.

Diagnostic accuracy of human chorionic gonadotropins (HCG) stimulation test in XY-disorders of sex development (XY-DSD) presented in Armed Forces Institute of Pathology.

OBJECTIVE: To determine diagnostic accuracy of human chorionic gonadotropins stimulation test in differentiating androgen insensitivity syndrome and 5-alpha reductase deficiency, keeping testosterone to dihydrotestosterone ratio as the gold standard. METHODS: The cross-sectional study was conducted at the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from January to December, 2016, and comprised patients aged 01 day to 20 years having XY chromosomes on karyotyping and with a spectrum of phenotypes. Blood samples were collected from each subject for basal serum testosterone, serum luteinizing hormone and serum follicular stimulating hormone level. Human chorionic gonadotropins stimulation test was performed in every subject as per the protocol. Sandwich chemiluminescence immunoassay technique was used to analyse serum samples. Serum dihydrotestosterone level was also detected to determine testosterone and dihydrotestosterone ratio. Data was analysed using SPSS 24. . RESULTS: Of the 104 subjects with a mean age of 1.78}0.95 years,96(92.3%) were diagnosed as cases of androgen insensitivity syndrome on the basis of human chorionic gonadotropins stimulation response level, which was 2-9 times of basal serum testosterone level. Also, 8(7.7%) subjects were diagnosed to have 5-alpha reductase deficiency syndrome. In such subjects, post-human chorionic gonadotropins response level of serum testosterone was more than 10 times of the basal level. CONCLUSIONS: The human chorionic gonadotropins stimulation test was found to be comparable to testosterone-to dihydrotestosterone ratio in differentiating between case of androgen insensitivity syndrome and 5-alpha reductase deficiency.

[Hypospadias induced by maternal exposure to di-n-butyl phthalate and its mechanisms in male rat offspring , , , , ,].

OBJECTIVE: To induce hypospadias in male rat offspring by maternal exposure to di-n-butyl phthalate (DBP) during late pregnancy and further investigate its mechanisms. METHODS: We randomly divided 20 pregnant rats into a DBP exposure and a control group, the former treated intragastrically with DBP while the latter with soybean oil at 750 mg per kilogram of the body weight per day from gestation days (GD) 14 to 18. On postnatal day (PND) 1, we recorded the incidence rate of hypospadias and observed the histopathological changes in the genital tubercle of the hypospadiac rats. We also measured the level of serum testosterone (T) by radioimmunoassay and determined the mRNA and protein expressions of the androgen receptor (AR), sonic hedgehog (Shh), bone morphogenetic protein 4 (Bmp4) and fibroblast growth factor 8 (Fgf8) in the genital tubercle by real-time PCR and Western blot. RESULTS: No hypospadiac male rats were found in the control group. The incidence rate of hypospadias in male offspring was 43.6% in the DBP-treatment group. Histological analysis confirmed hypospadiac malformation. The serum testosterone concentration was decreased in the hypospadiac male rats as compared with the controls (ï¼»0.49 ± 0.05ï¼½ vs ï¼»1.12 ± 0.05ï¼½ ng/ml, P <0.05). The mRNA expressions of AR, Shh, Bmp4 and Fgf8 in the genital tubercle were significantly lower in the hypospadiac male rats than in the controls (AR: 0.50 ± 0.05 vs 1.00 ± 0.12, P <0.05; Shh: 0.65 ± 0.07 vs 1.00 ± 0.15, P <0.05; Bmp4: 0.42 ± 0.05 vs 1.00 ± 0.13, P <0.05; Fgf8: 0.46 ± 0.04 vs 1.00 ± 0.12, P <0.05), and so were their protein expressions (AR: 0.34 ± 0.05 vs 1.00 ± 0.09, P <0.05; Shh: 0.51 ± 0.07 vs 1.00 ± 0.12, P <0.05; Bmp4: 0.43 ± 0.05 vs 1.00 ± 0.11, P <0.05; Fgf8: 0.57 ± 0.04 vs 1.00 ± 0.13, P <0.05). CONCLUSIONS: Maternal exposure to DBP during late pregnancy can induce hypospadias in the male rat offspring. DBP affects the development of the genital tubercle by reducing the serum T concentration and expressions of AR, Shh, Bmp4 and Fgf8 in the genital tubercle, which might underlie the mechanism of DBP inducing hypospadias.

Polymorphism of 3' UTR of MAMLD1 gene is also associated with increased risk of isolated hypospadias in Indian children: a preliminary report.

OBJECTIVE: To study MAMLD1 gene polymorphisms, serum LH and testosterone levels amongst Indian children with isolated hypospadias (IH) and controls. MATERIALS AND METHODS: Screening of the MAMLD1 gene was performed by PCR sequencing method in 100 Indian children aged 0-12 years presenting with IH and 100 controls. LH and testosterone hormone levels were also assessed (categorized in four age-wise groups). RESULTS: IH subjects had significantly higher incidence of MAMLD1 polymorphism as compared to controls (33 vs 15 %, p = 0.01). Of various genomic variants identified in this study, the noteworthy novel ones were missense mutation P299A and single nucleotide polymorphism c.2960C>T in 3' UTR of Exon 7. While p 299A was found to cause protein structural instability consequent to amino acid change, eighty percent subjects with c.2960C>T in 3' UTR of Exon 7 (corresponding to newly discovered currently non-validated exon 11) were found to have lower testosterone levels when compared with their age group mean. IH showed statistically higher incidence of c.2960C>T in comparison to controls (22 vs 10 %, p value 0.046) and about 2.5-folds higher risk of this anomaly. CONCLUSION: Occurrence of MAMDL1 gene polymorphisms, specially of c.2960C>T in 3' UTR of its exon 7 is associated with a higher risk of IH in Indian children, probably by lowering androgenic levels.

[Sexual development of boys with hypospadias].

The article presents the results of a clinical evaluation of 39 boys with hypospadias aged 10-15 years. The examination included clinical assessment of pubertal development, and Doppler ultrasound scan of the gonads, transrectal ultrasound of the prostate in adolescents over 14 years, the definition of serum levels of gonadotropins, sex steroids and inhibin B. Puberty in boys with hypospadias is characterized by later appearance of pubarhe, microphallus, lack of testicular blood flow, and hypotrophy of the prostate. Statistically significant difference in sexual development of boys with penile and scrotal hypospadias was detected. On the basis of the hormonal examination, a violation of function of Sertoli cells in 43% of boys with the penile hypospadias and in 68% with scrotal hypospadias was identified. Leydig cell dysfunction was not found.

Children with isolated hypospadias have different hormonal profile compared to those with associated anomalies.

AIM: The objective of this study is to compare the hormonal profile of children with isolated hypospadias to controls and hypospadiacs with associated anomalies. STUDY DESIGN: Prospective observation at a tertiary referral hospital. STUDY SUBJECTS: One hundred consecutive children (0-12 years) with isolated hypospadias (H), 23 with hypospadias and associated anomalies (HO). CONTROLS: One hundred children (0-12 years) without any genitourinary/endocrine abnormalities (C). PROCEDURE: Prehuman chorionic gonadotropin (HCG) and post-HCG fasting blood samples were drawn for estimation of serum gonadotropins, dehydroepiandrosterone sulfate (DHEA-S), estrogen (E), progesterone (P), and testosterone (T) and dihydrotestosterone (DHT). STATISTICAL ANALYSIS: Differences in hormonal levels between controls and subjects were computed with p < or = 0.05 as significant. RESULTS: Compared with controls, "H" had significantly higher follicular stimulating hormone (FSH) (1.37 vs. 1.29 mIU/mL p=0.01), lower estrogen (8.08 vs. 13.78 pg/mL, p=0.00), and lower DHEA-S (27.34 vs. 40.24 microg/dL, p=0.03) levels; HO had higher FSH, lower basal T (0.13 vs. 0.46 ng/mL, p=0.01), and lower peak testosterone (1.53 vs. 2.32 ng/mL, p=0.01). "HO" had lower androgens (basal T, 0.13 vs. 0.29 ng/mL, p=0.03; peak T, 1.53 vs. 2.36 ng/mL, p=0.01), and higher estrogen (12.56 vs. 8.08 pg/mL, p=0.001) and progesterone (0.46 vs. 0.31 ng/mL, p=0.04) levels in comparison with H. CONCLUSION: Consistently lower output of androgens among HO explains the association of other anomalies (generally undescended testes) in them. High FSH among hypospadiacs hints at the possibility of Sertoli cell dysfunction and may have long-lasting sequelae for reproductive functions during adulthood. However, Leydig cell functions are affected more among HO.

The association between some endocrine disruptors and hypospadias in biological samples.

Hypospadias is a birth defect found in boys in which the urinary tract opening is not at the tip of the penis. The etiology of hypospadias is still unidentified, but endocrine disruptors are considered as one possible cause of hypospadias. In this study, target endocrine disruptor compounds were established for an assay. The target compounds included 5 phthalates (di-(2-ethylhexyl)phthalate (DEHP), di-n-butyl-phthalate (DBP), mono-(2- ethylhexyl) phthalate (MEHP), mono-n-butyl-phthalate (MBP) and phthalic acid (PA)), 2 alkylphenols (n-nonylphenol (n-NP) and t-octylphenol (t-OP)) and bisphenol A. The association between these 8 endocrine disruptors and hypospadias was studied. The levels of endocrine disruptors in the urine and plasma of a control group were compared with those of a patient group. DEHP (P = 0.006) and n-NP (P = 7.26e-6) in the urine samples and PA (P = 0.009) and BPA (P = 7.22e-10) in the plasma samples showed a significant association with hypospadias. The levels of endocrine disruptors in the urine and plasma of the mothers were also compared to those of the patients to investigate the metastasis of the endocrine disruptors from the mother. These levels did not, however, show a relationship with hypospadias (R(2) = 0.001-0.563).

Endocrine assessment of prepubertal boys with a history of cryptorchidism and/or hypospadias: a pilot study.

PURPOSE: Four disorders, including poor semen quality, testicular cancer, cryptorchidism and hypospadias, are thought to represent testicular dysgenesis syndrome and have been hypothesized to share a common etiology. We predicted testicular function in prepubertal boys with a history of cryptorchidism and/or hypospadias by measuring serum hormone levels. MATERIALS AND METHODS: A total of 82 prepubertal boys who underwent orchiopexy and/or hypospadias repair in childhood were enrolled in the study. Patients were surgically treated for cryptorchidism (23 in group 1), hypospadias (49 in group 2), cryptorchidism and hypospadias (10 in group 3), and hydrocele testis (7 in control group 4). Serum hormones, including luteinizing hormone, follicle-stimulating hormone and total testosterone, were measured separately by age less than 12.5, 12.5 to 13.5 and greater than 13.5 years, and by Tanner pubertal stage. RESULTS: Follicle-stimulating hormone in group 3 was significantly higher than in groups 1, 2 and 4 at ages 12.5 to 13.5 and greater than 13.5 years, and for Tanner stages 2 and 3 (p <0.05). However, luteinizing hormone and testosterone did not differ among the groups regardless of age or Tanner stage. Group 3 patients had significantly higher follicle-stimulating hormone regardless of the severity of cryptorchidism or hypospadias. CONCLUSIONS: Data suggest that testicular function in patients with cryptorchidism plus hypospadias is more severely impaired than that in patients with cryptorchidism or hypospadias, lending clinical support to the testicular dysgenesis syndrome hypothesis of a common origin.

Long-term outcome of pituitary-gonadal axis and gonadal growth in patients with hypospadias at puberty.

PURPOSE: Reports of pubertal hormonal and gonadal status in patients with hypospadias are scarce. We evaluated the pituitary-gonadal axis and gonadal growth in patients with hypospadias at puberty. MATERIALS AND METHODS: We retrospectively reviewed serum luteinizing hormone, follicle-stimulating hormone, testosterone and testicular volume at puberty (age 15 years or greater) in the medical charts of patients with hypospadias treated since 1986 and followed at our institution. RESULTS: Enrolled in this study were 43 patients with a mean age at evaluation of 17.6 years (range 15.1 to 22.8). Of these patients 14 and 29 were treated for mild and severe hypospadias, respectively. Six patients with severe hypospadias underwent bilateral orchiopexy for bilateral undescended testes. All patients were Tanner stage 4 to 5 at evaluation. Of 14 mild hypospadias cases we noted hypergonadotropic hypogonadism, hypogonadotropic hypogonadism, decreased luteinizing hormone and decreased testosterone in 1 each (7% each). Of 23 severe hypospadias cases without bilateral undescended testes we noted hypergonadotropic hypogonadism, partial androgen insensitivity syndrome and decreased testosterone in 2 (9%), 1 (4%) and 1 (4%), respectively. Of 6 patients with severe hypospadias and bilateral undescended testes we noted hypergonadotropic hypogonadism in 1 (17%) and increased luteinizing hormone with normal testosterone in 2 (33%). Testicular volume less than 10 ml with increased follicle-stimulating hormone was identified in 7 of 43 patients, including 1 of 14 (7%) with mild hypospadias, 3 of 23 (13%) with severe hypospadias without bilateral undescended testes and 3 of 6 (50%) with severe hypospadias and bilateral undescended testes. CONCLUSIONS: Our study revealed endocrine dysfunction in patients with mild and severe hypospadias at puberty even without an undescended testis. Of these patients those with severe hypospadias and an undescended testis may be at higher risk for impaired spermatogenesis.

Genetic Analysis of 25 Patients with 5α-Reductase Deficiency in Chinese Population.

BACKGROUND: A deficiency in steroid 5α-reductase type 2 is an autosomal recessive disorder. Affected individuals manifested ambiguous genitalia, which is caused by decreased dihydrotestosterone (DHT) synthesis in the fetus. METHODS: We analyzed 25 patients with 5α-reductase deficiency in China. Seventeen of the 25 patients (68%) were initially raised as females. Sixteen patients changed their social gender from female to male after puberty. RESULTS: Eighteen mutations were identified in these patients. p.Gly203Ser and p.Gln6∗ were found to be the most prevalent mutations. On the basis of the genotype of these patients, we divided them into different groups. There was no significant difference in hormone levels and external masculinization score (EMS) in patients with or without these prevalent mutations. Twelve common single-nucleotide polymorphisms (SNPs) near the p.Gln6∗ mutation were chosen for haplotype analysis. Three haplotypes were observed in 6 patients who had the p.Gln6∗ mutation (12 alleles). CONCLUSION: We analyzed mutations of the SRD5A2 gene in Chinese patients with 5α-reductase deficiency. Although hotspot mutations exist, no founder effect of prevalent mutations in the SRD5A2 gene was detected in the Chinese population.

Hypospadias in six dogs.

Six dogs, five males and one hermaphrodite, were diagnosed with hypospadias. Two of the five males had the penile form of the condition, two had the perineal form and one had the glandular form; the hermaphrodite had the scrotal form. The hermaphrodite had no prostate gland and no right testicle; it had a normal right ovary and horn of the uterus but the left horn was joined to the testicle. Its karyotype showed 78 chromosomes, all in metaphase, and two typical sex chromosomes X and Y.

Association Between Extra-Genital Congenital Anomalies and Hypospadias Outcome.

Extra-genital congenital anomalies are often present in cases of hypospadias, but it is unclear whether they have an association with the outcome of hypospadias surgery. The aim of this study was to review all hypospadias cases that had surgery between 2009 and 2015 at a single centre and identify clinical determinants of the surgical outcome. An extra-genital congenital anomaly was reported in 139 (22%) boys and 62 (10%) had more than 1 anomaly. Of the 626 boys, 54 (9%), including 44 with proximal hypospadias, had endocrine as well as limited genetic evaluation. Of these, 10 (19%) had a biochemical evidence of hypogonadism and 5 (9%) had a molecular genetic abnormality. At least 1 complication was reported in 167 (27%) patients, with 20% of complications (most frequently fistula) occurring after 2 years of surgery. The severity of hypospadias and the existence of other anomalies were clinical factors that were independently associated with an increased risk of complications (p < 0.001). In conclusion, complications following surgery are more likely in those cases that are proximal or who have additional extra-genital anomalies. To understand the biological basis of these complications, there is a greater need to understand the aetiology of such cases.

Anogenital distance and reproductive outcomes in 9- to 11-year-old boys: the INMA-Granada cohort study.

BACKGROUND: Studies examining the association of anogenital distance (AGD), a biomarker of prenatal androgen exposure, with sexual development in children are lacking. OBJECTIVE: To assess the association between AGD measures and reproductive outcomes, including puberty onset, testicular volume, reproductive hormone levels, and urogenital malformations in boys aged 9-11 years. MATERIALS AND METHODS: A cross-sectional study was conducted among children belonging to the Spanish Environment and Childhood (INMA) Project, a population-based birth cohort study. The present sample included 279 boys for whom data were available on AGD, pubertal stage, testicular volume, and relevant covariates. Out of the boys with AGD data, 187 provided a blood sample for hormone analysis. AGD was measured from the center of the anus to the base of the scrotum. Pubertal development was assessed according to Tanner stage of genital development (G1-G5), and testicular volume was measured with an orchidometer. RESULTS: After adjusting for potential confounders, logistic regression analysis showed that AGD was positively associated with testicular volume but not with Tanner stage (>G1 vs. G1), serum hormone levels, or undescended testis. Regardless of their age, body mass index, and Tanner stage (G1 or >G1), boys with longer AGD showed increased odds of a testicular volume >3 mL (OR = 1.06, 95%CI = 1.00-1.19 per 10% increment in AGD; and OR = 3.14, 95%CI = 0.99-9.94 for AGD >42 mm vs. <33 mm). DISCUSSION: Longer AGD was associated with testicular growth, an indicator of gonadarche, but not with other reproductive outcomes. CONCLUSIONS: Although AGD was positively associated with testicular volume, it remains unclear whether AGD predicts testis size at puberty or is related to puberty onset.

5-α-Reductase type 2 deficiency: is there a genotype-phenotype correlation? A review.

5-α-Reductase type 2 enzyme catalyzes the conversion of testosterone into dihydrotestosterone, a potent androgen responsible for male sexual development during the fetal period and later during puberty. Its deficiency causes an autosomal recessive disorder of sex development characterized by a wide range of under-virilization of external genitalia in patients with a 46,XY karyotype. Mutations in the SRD5A2 gene cause 5-α-Reductase deficiency; although it is an infrequent disorder, it has been reported worldwide, with mutational heterogeneity. Furthermore, it has been proposed that there is no genotype-phenotype correlation, even in patients carrying the same mutation. The aim of this review was to perform an extensive search in various databases and to select those articles with a comprehensive genotype and phenotype description of the patients, classifying their phenotypes using the external masculinization score (EMS). Thus, it was possible to objectively compare the eventual genotype-phenotype correlation between them. The analysis showed that for most of the studied mutations no correlation can be established, although the specific location of the mutation in the protein has an effect on the severity of the phenotype. Nevertheless, even in patients carrying the same homozygous mutation, a variable phenotype was observed, suggesting that additional genetic factors might be influencing it. Due to the clinical variability of the disorder, an accurate diagnosis and adequate medical management might be difficult to carry out, as is highlighted in the review.

Comparison between two inhibin B ELISA assays in 46,XY testicular disorders of sex development (DSD) with normal testosterone secretion.

BACKGROUND: Inhibin B is a hormone produced by the Sertoli cells that can provide important information for the investigation of disorders of sex development (DSD) with 46,XY karyotype. The aim of this study is to compare two enzyme-linked immunosorbent assay (ELISA) assays for dosage of serum inhibin B in patients with 46,XY DSD with normal testosterone secretion. METHODS: Twenty-nine patients with 46,XY DSD and normal testosterone secretion (partial androgen insensitivity syndrome [PAIS] [n=8]; 5α-reductase deficiency [n=7] and idiopathic 46,XY DSD [n=14]) were included. Molecular analysis of the AR and SRD5A2 genes were performed in all patients and the NR5A1 gene analysis in the idiopathic group. Measurements of inhibin B were performed by two second-generation ELISA assays (Beckman-Coulter and AnshLabs). Assays were compared using the interclass correlation coefficient (ICC) and the Bland-Altman method. RESULTS: ICC was 0.915 [95% confidence interval (CI): 0.828-0.959], however, a discrepancy was observed between trials, which is more evident among higher values when analyzed by the Bland-Altman method. CONCLUSIONS: It is recommended to perform the inhibin B measurement always using the same ELISA kit when several evaluations are required for a specific patient.

Study on developmental abnormalities in hypospadiac male rats induced by maternal exposure to di-n-butyl phthalate (DBP).

The objective of this study was to establish a hypospadiac rat model by maternal exposure to di-n-butyl phthalate (DBP) and to evaluate the developmental abnormalities of hypospadiac male rats. Timed-pregnant rats were given DBP by gastric intubation at doses of 0, 250, 500, 750 or 1000 mg/kg body weight (bw)/day from gestation day (GD) 14 to 18 to establish a hypospadiac rat model. The hypospadias was observed in the 500 and 750 mg/kg bw/day groups, the incidence of which was 6.8 and 41.3%, respectively. Transverse serial histological analysis of genitalia of hypospadiac male rats confirmed the malformation. With exposed dose increasing, the serum testosterone (T) levels of male rats inversely decreased, and in the same dosage group the serum T levels of hypospadiac rats were significantly lower than the levels of nonhypospadiac counterparts. The other reproductive lesions such as cryptorchidism and decreased ratio of anogenital distance/body weight (AGD/bw) were also observed. Autopsy analysis revealed the development of reproductive organs (prostate, testes, epididymis, pituitary gland) and nonreproductive organs (adrenal gland, liver, kidney, heart, spleen) of hypospadiac rats and nonhypospadiac counterparts. The results indicated that the reproductive system and developmental condition of hypospadiac male offspring were damaged severely by DBP.