Alterations in gene expression during sexual differentiation in androgen receptor knockout mice induced by environmental endocrine disruptors.

In the present study, we aimed to explore the effect of environmental endocrine disruptors (EEDs) on sexual differentiation in androgen receptor (AR)-/-, AR+/- and AR+/+ male mice. By using a Cre-loxP conditional knockout strategy, we generated AR knockout mice. By mating flox-AR female mice with AR-Cre male mice, the offspring male mice which were produced were examined. Mice not subjected to any type of intervention were used as the controls. Furthermore, male mice of different genotypes were selected and further divided into subgroups as follows: the control group, bisphenol A (BPA) group and the dibutyl phthalate [corrected] (DBP) group. The expression of the Wilms tumor 1 (WT1), lutropin/choriogonadotropin receptor (LHR), 17-ß-hydroxysteroid dehydrogenase type 3 (17ßHSD3) and steroid-5-alpha-reductase, alpha polypeptide 2 (SRD5A2) genes was determined by RT-qPCR and western blot analysis. There was no statistically significant difference in the weight of the mice between the control group and the knockout group (P>0.05). The results revealed that, compared with the control group, in the knockout group, anogenital distance was shortened, and testicular weight and testosterone levels were decreased; estradiol levels were elevated; the differences were statistically significant (P<0.05). In the group of AR+/- male mice exposed to 100 mg/l EEDs, hypospadias was successfully induced, suggesting that EEDs are involved in the embryonic stage of sexual development in male mice. The quantitative detection of WT1, LHR, 17ßHSD3 and SRD5A2 gene expression by RT-qPCR and western blot analysis indicated that these genes were significantly downregulated in the mice in the BPA group. In conclusion, exposure to EEDs induces hypospadias in heterozygous and wild-type male mice offspring during sexual differentiation, but has no effect on homozygous offspring. Therefore, EEDs play an important role during the third stage of sexual differentiation.

Subtrochanteric valgus osteotomy with monolateral external fixator in hips for patients with severe cerebral palsy.

Subtrochanteric valgus osteotomy has been used for painful hip joint dislocation in patients with severe cerebral palsy. The goal of this study was to evaluate 11 patients (17 hips) with severe cerebral palsy who had chronically dislocated and painful hips treated with subtrochanteric valgus osteotomy using a monolateral external fixator. A retrospective review was performed of 11 patients (average age, 17.8 years) with severe quadriplegic cerebral palsy with flexion-adduction contractures due to chronically dislocated and painful hips. A subtrochanteric valgus osteotomy with a monolateral fixator was performed in all patients. Patients were analyzed clinicoradiologically, and caregivers were asked about ease of handling, transfers, and perineal care. At an average follow-up of 37 months (range, 14-72 months), all caregivers were satisfied with the surgery and felt that their child was more comfortable and could sit with support for a longer time period and that perineal care, wheelchair mobilization, and transfers were much easier. A total of 11 complications in 7 patients were observed, including pin-tract infections, delayed consolidation, abduction deformity, and hypostatic pneumonia. The complication rate of subtrochanteric valgus osteotomy was comparable with other methods, and this method had the advantage of shorter surgical time, ease of application, no internal implant with lesser chance of infection or heterotopic calcification, and less intraoperative blood loss with less morbidity.