Assessing the impact of in-utero exposures: potential effects of paracetamol on male reproductive development.

Human male reproductive disorders (cryptorchidism, hypospadias, testicular cancer and low sperm counts) are common and some may be increasing in incidence worldwide. These associated disorders can arise from subnormal testosterone production during fetal life. This has resulted in a focus on in-utero environmental influences that may result in reproductive effects on the offspring in later life. Over recent years, there has been a dramatic increase in the scientific literature describing associations between in-utero environmental exposures (eg, industrial chemicals and pharmaceuticals) and subsequent reproductive outcomes in male offspring. This includes studies investigating a potential role for in-utero analgesic exposure(s) on the fetal testis; however, providing definitive evidence of such effects presents numerous challenges. In this review, we describe an approach to assessing the potential clinical relevance of in-utero (and postnatal) environmental exposures on subsequent male reproductive function using exposure to the analgesic paracetamol as an example.

Penile biometry on prenatal magnetic resonance imaging.

OBJECTIVE: In view of the implementation of magnetic resonance imaging (MRI) as an adjunct to ultrasonography in prenatal diagnosis, this study sought to demonstrate normal penile growth on prenatal MRI. METHODS: This was a retrospective study of MRI of 194 male fetuses (18-34 weeks' gestation) with normal anatomy or minor abnormalities. On sagittal T2-weighted MRI sequences, we measured penile length from the glans tip to the scrotal edge (outer length) and from the glans tip to the symphyseal border (total length). Descriptive statistics, as well as correlation and regression analysis, were used to evaluate penile length in relation to gestation. T-tests were calculated to compare mean outer/total length on MRI with published ultrasound data. RESULTS: Mean length values, including 95% CIs and percentiles, were defined. Penile length as a function of gestational age was expressed by the following regression equations: outer mean length = - 5.514 + 0.622 × gestational age in weeks; total mean length = - 8.865 + 1.312× gestational age in weeks. The correlation coefficients, r = 0.532 and r = 0.751, respectively, were statistically significant (P < 0.001). Comparison of outer penile length on MRI with published ultrasound penile length data showed no significant differences, while total penile length on MRI was significantly greater than ultrasound penile length (P < 0.001). CONCLUSION: Our MRI results provide a reference range of fetal penile length, which, in addition to ultrasonography, may be helpful in the identification of genital anomalies. Outer penile length on MRI is equivalent to penile length measured on ultrasound, whereas total length is significantly greater.

Cumulative effects of in utero administration of mixtures of "antiandrogens" on male rat reproductive development.

Although risk assessments are typically conducted on a chemical-by-chemical basis, the 1996 Food Quality Protection Act (FQPA) required the Environmental Protection Agency (EPA) to consider cumulative risk of chemicals that act via a common mechanism of toxicity. To this end, we are conducting studies with mixtures to provide a framework for assessing the cumulative effects of "antiandrogenic" chemicals. Rats were dosed during pregnancy with antiandrogens singly or in pairs at dosage levels equivalent to about one half of the ED50 for hypospadias or epididymal agenesis. The pairs include: AR antagonists (vinclozolin plus procymidone), phthalate esters (DBP plus BBP and DEHP plus DBP), a phthalate ester plus an AR antagonist (DBP plus procymidone), and linuron plus BBP. We predicted that each chemical by itself would induce few malformations; however, by mixing any two chemicals together, about 50% of the males would be malformed. All binary combinations produced cumulative, dose-additive effects on the androgen-dependent tissues. We also conducted a mixture study combining seven "antiandrogens" together. These chemicals elicit antiandrogenic effects at two different sites in the androgen signaling pathway (i.e., AR antagonist or inhibition of androgen synthesis). In this study, the complex mixture behaved in a dose-additive manner. Our results indicate that compounds that act by disparate mechanisms of toxicity display cumulative, dose-additive effects when present in combination.

[Prenatal diagnosis of an inguino-scrotal hernia in a fetus with trisomy 18]. / Pränatale Diagnose einer Skrotalhernie bei einem Feten mit Trisomie 18.

In spite of its prevalence in neonates, an inguino-scrotal hernia is a rarely detected condition in prenatal life. The sonographic findings, i. e., a scrotal mass with intestinal peristalsis, the differential diagnosis, and possible associations between a scrotal hernia and chromosomal aberrations are described by presenting the case of a fetus with trisomy 18 and major structural anomalies.

Prenatal evaluation of a scrotal mass using a high-frequency probe in the diagnosis of inguinoscrotal hernia.

Whereas inguinal hernia is a common pediatric disease, fetal inguinal hernia is rarely diagnosed because intra-abdominal pressure usually occurs only after birth. We report a case of prenatal diagnosis of a scrotal mass at 35 weeks' gestation. The initial differential diagnosis included hydrocele, testicular teratoma and testicular torsion, but inguinoscrotal hernia was considered the most likely diagnosis when further ultrasound imaging using a high-frequency probe demonstrated bowel loop movements around the mesenteric artery. This diagnosis was confirmed postnatally.

A unique radiological pentad of mesonephric duct abnormalities in a young man presenting with testicular swelling.

Cystic dysplasia of the rete testis with associated ipsilateral renal agenesis is a very rare congenital abnormality, mainly described in the paediatric literature. In addition, the presence of a seminal vesicle cyst with ipsilateral renal agenesis is a rare but well-described entity. We present an adult who was found to have a unique pentad of mesonephric duct abnormalities on radiological imaging, including cystic dysplasia of the rete testis, seminal vesicle cyst, ipsilateral renal agenesis, partial hemitrigonal development and epididymal dilatation. We review and discuss the relevant literature of this case and discuss in detail the embryological basis for this unusual combination of findings.

Environment, testicular dysgenesis and carcinoma in situ testis.

The testicular dysgenesis syndrome (TDS) hypothesis proposes that a proportion of the male reproductive disorders-cryptorchidism, hypospadias, infertility and testicular cancer-may be symptoms of one underlying developmental disease, TDS, which is most likely a result of disturbed gonadal development in the embryo. TDS may be caused by genetic factors, environmental/life-style factors, or a combination of both. Some rare disorders of sex development of genetic origin are among the best-known examples of severe TDS. Among the environmental and life-style factors that are suspected to influence the hormonal milieu of the developing gonad are the endocrine disrupters. A prenatal exposure to commonly used chemicals, e.g. phthalates, may result in a TDS-like phenotype in rats. Currently, this animal model is the best model for TDS. In humans the situation is much more complex, and TDS exists in a wide range of phenotypes: from the mildest and most common form, in which impaired spermatogenesis is the only symptom, to the most severe cases, in which the patient may develop testicular cancer. It is of great importance that clinicians in different specialties treating patients with TDS are aware of the association between the different symptoms.

Atypical sonographic presentation of fetal unilateral inguinoscrotal hernia in a multiple gestation.

Ultrasonographic demonstration of bowel peristalsis within the fetal scrotum has been described as a pathognomonic sign of inguinoscrotal bowel herniation. We present the sonographic features and neonatal outcome of a fetus with a scrotal mass seen at 34 weeks of gestation in a twin pregnancy. This mass was diagnosed postnatally as a non-reducible inguinoscrotal hernia, in which bowel peristalsis had not been observed by real-time ultrasound in utero.

Median raphe cysts of the genitalia.

We report 2 recent cases of midline cysts of the genitoperineal raphe in children, and discuss the embryogenesis, diagnosis and management. Congenital anomalies of an unclear etiology, median raphe cysts are probably more common than has been reported in the literature. Medical attention is usually sought for secondary infections or pain with intercourse. Awareness and prompt identification of these entities by urologists are essential for proper management when differentiation from other more formidable lesions, including urethral diverticula, becomes important. Simple surgical excision is effective in most cases.

Agenesis of kidney associated with malformations of the seminal vesicle. Various clinical presentations.

Ureteral seminal vesicle anomaly associated with ipsilateral renal agenesis is a rare occurrence. Cystic anomaly of the seminal vesicle may be asymptomatic or discovered by rectal examination and cystoscopy for evaluation of bladder irritative symptoms, perineal and testicular pain, ejaculatory disturbances and rarely infertility. The condition was diagnosed in three patients with various clinical presentations.

Tubular embryonal remnants in the human spermatic cord.

The spermatic cords (SCs) obtained from: (a) autopsies of 67 adults and 50 children; (b) 3 fetuses; (c) 12 surgical specimens from 9 adults and 3 children with testicular tumors, and (d) 26 surgical specimens (14 adults and 12 children) with diagnosis of SC cysts, were studied by light microscopy. The histological study revealed the occurrence of tubular embryonal remnants (TERs) in 19 autopsied adults, 14 autopsied children, 3 fetuses, 2 surgical specimens (1 adult and 1 child) owing to testicular tumors, and 6 surgical specimens with diagnosis of SC cysts. The TERs were found in the low, middle or high thirds of the SC and consisted of a cuboidal or columnar, often ciliated epithelium surrounded by connective tissue. In the 3 fetuses and in 3 autopsied children renal glomeruli were found in close relation with the TERs. In 2 cases of SCs showing cysts and TERs both structures contained spermatozoa. The histological pattern of the TERs suggest that they are wolffian derivatives which might give rise to SC cysts.

Seminal vesicle cyst and ipsilateral renal agenesis.

A case of seminal vesicle cyst with ipsilateral agenesis is presented. The embryologic events, clinical symptoms, and diagnosis are discussed, emphasizing the value of sonography and computer tomography in identifying the cyst. Surgical resection is the treatment of choice.

Embryological and diagnostic aspects of seminal vesicle cysts associated with upper urinary tract malformation.

Congenital seminal vesicle cysts represent a rare but illustrative type of embryological malformation. They often are combined with ipsilateral upper urinary tract abnormalities. In most of the cases described in the literature the diagnosis has been made with rather invasive procedures. On the basis of our experience with 3 cases we recommend pelvic ultrasonography as the initial study in patients in whom such a malformation is suspected. Although other radiological procedures may be required to confirm the diagnosis, this approach appears to be cost-effective and accurate in most instances. The treatment of such malformations should be restricted to symptomatic cases and usually consists of vesiculectomy with or without removal of the ipsilateral dysplastic or hypoplastic kidney.