The balance between androgens and estrogens is very important in the development of the prostate, and even small changes in estrogen levels, including those of estrogen-mimicking chemicals, can lead to serious changes. Bisphenol A (BPA), an endocrine-disrupting chemical, is a well-known, ubiquitous, estrogenic chemical. To investigate the effects of fetal exposure to low-dose BPA on the development of the prostate, we examined alterations of the in situ sex steroid hormonal environment in the mouse urogenital sinus (UGS). In the BPA-treated UGS, estradiol (E(2)) levels and CYP19A1 (cytochrome P450 aromatase) activity were significantly increased compared with those of the untreated and diethylstilbestrol (DES)-treated UGS. The mRNAs of steroidogenic enzymes, Cyp19a1 and Cyp11a1, and the sex-determining gene, Nr5a1, were up-regulated specifically in the BPA-treated group. The up-regulation of mRNAs was observed in the mesenchymal component of the UGS as well as in the cerebellum, heart, kidney, and ovary but not in the testis. The number of aromatase-expressing mesenchymal cells in the BPA-treated UGS was approximately twice that in the untreated and DES-treated UGS. The up-regulation of Esrrg mRNA was observed in organs for which mRNAs of steroidogenic enzymes were also up-regulated. We demonstrate here that fetal exposure to low-dose BPA has the unique action of increasing in situ E(2) levels and CYP19A1 (aromatase) activity in the mouse UGS. Our data suggest that BPA might interact with in situ steroidogenesis by altering tissue components, such as the accumulation of aromatase-expressing mesenchymal cells, in particular organs.

Activation of tumor-stromal interactions is considered to play a critical role in the promotion of tumorigenesis. To discover new therapeutic targets for hormone-refractory prostate tumor growth under androgen ablation therapy, androgen-sensitive LNCaP cells and the derived sublines, E9 (androgen-low-sensitive), and AIDL (androgen-insensitive), were recombined with androgendependent embryonic rat urogenital sinus mesenchyme (UGM). Tumors of E9CUGM and AIDLCUGM were approximately three times as large as those of LNCaPCUGM. Tumors grown in castrated hosts exhibited reduced growth as compared with those in intact hosts. However, in castrated hosts, E9CUGM and AIDLCUGM tumors were still approximately twice as large as those of LNCaPCUGM. Cell proliferation in tumors of E9CUGM and AIDLCUGM grown in castrated host, was significantly higher than that in tumors of LNCaPCUGM. In vitro, expression of fibroblast growth factor (FGF)-2 and IGF-I, but not FGF-7 mRNA, was significantly reduced in UGM under androgen starvation. In cell culture, E9 cells were responsive to FGF-2 and FGF-7 stimulation, while AIDL responded to FGF-7 and IGF-1. Expression of FGFR1 and FGFR2 was considerably higher in E9 than those in LNCaP, similarly expression of FGFR2 and IGF-IR were elevated in AIDL. These data suggest that activation of prostate cancer cell growth through growth factor receptor expression may result in the activity of otherwise androgenindependent stromal growth factor signals such as FGF-7 under conditions of androgen ablation.

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Objectives To evaluate subjective and objective outcomes, complication, recurrence, and reoperation rates after transvaginal mesh surgery for the management of pelvic organ prolapse. Methods This was a retrospective analysis of transvaginal mesh surgery carried out using self‐cut mesh measuring subjective outcomes using validated questionnaires, and objective outcomes using Pelvic Organ Prolapse Quantification. Patients diagnosed with stage ≥2 pelvic organ prolapse were counseled about all possible surgical options. After thorough explanation about the benefits and risks during transvaginal mesh surgery, patients who gave signed consent were scheduled for surgery and evaluated at 1 and 3 years postoperatively. Results We included 101 patients who completed a minimum of 3‐year follow up. One year and 3‐year follow up showed significant improvement both on subjective and objective outcomes. Recurrences were observed in three patients (3%), with one (1%) patient undergoing reoperation. One case (1%) of intraoperative complication (bladder injury) and four cases (4%) of postoperative complications (two mesh exposure, one hematoma and one significant increase in post‐voiding residual) were recorded. Overall patients’ satisfaction was positive. Conclusions Transvaginal mesh surgery using self‐cut mesh is associated with significant improvement in both subjective and objective outcomes, offering low recurrence and complication rates, and high patient satisfaction rates. It can be a safe, effective and cost‐efficient option not only for recurrence cases, but also as primary management of pelvic organ prolapse using a standardized technique and proper patient selection.

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