Peri- and Postpubertal Estrogen Exposures of Female Mice Optimize Uterine Responses Later in Life.

At birth, all female mice, including those that either lack estrogen receptor α (ERα-knockout) or that express mutated forms of ERα (AF2ERKI), have a hypoplastic uterus. However, uterine growth and development that normally accompany pubertal maturation does not occur in ERα-knockout or AF2ERKI mice, indicating ERα-mediated estrogen (E2) signaling is essential for this process. Mice that lack Cyp19 (aromatase knockout, ArKO mice), an enzyme critical for E2 synthesis, are unable to make E2 and lack pubertal uterine development. A single injection of E2 into ovariectomized adult (10 weeks old) females normally results in uterine epithelial cell proliferation; however, we observe that although ERα is present in the ArKO uterine cells, no proliferative response is seen. We assessed the impact of exposing ArKO mice to E2 during pubertal and postpubertal windows and observed that E2-exposed ArKO mice acquired growth responsiveness. Analysis of differential gene expression between unexposed ArKO samples and samples from animals exhibiting the ability to mount an E2-induced uterine growth response (wild-type [WT] or E2-exposed ArKO) revealed activation of enhancer of zeste homolog 2 (EZH2) and heart- and neural crest derivatives-expressed protein 2 (HAND2) signaling and inhibition of GLI Family Zinc Finger 1 (GLI1) responses. EZH2 and HAND2 are known to inhibit uterine growth, and GLI1 is involved in Indian hedgehog signaling, which is a positive mediator of uterine response. Finally, we show that exposure of ArKO females to dietary phytoestrogens results in their acquisition of uterine growth competence. Altogether, our findings suggest that pubertal levels of endogenous and exogenous estrogens impact biological function of uterine cells later in life via ERα-dependent mechanisms.

Salt supplementation ameliorates developmental kidney defects in COX-2-/- mice.

Deficiency of cyclooxygenase-2 (COX-2) activity in the early postnatal period causes impairment of kidney development leading to kidney insufficiency. We hypothesize that impaired NaCl reabsorption during the first days of life is a substantial cause for nephrogenic defects observed in COX-2-/- mice and that salt supplementation corrects these defects. Daily injections of NaCl (0.8 mg·g-1·day-1) for the first 10 days after birth ameliorated impaired kidney development in COX-2-/- pups resulting in an increase in glomerular size and fewer immature superficial glomeruli. However, impaired renal subcortical growth was not corrected. Increasing renal tubular flow by volume load or injections of KCl did not relieve the renal histomorphological damage. Administration of torsemide and spironolactone also affected nephrogenesis resulting in diminished glomeruli and cortical thinning. Treatment of COX-2-/- pups with NaCl/DOCA caused a stronger mitigation of glomerular size and induced a slight but significant growth of cortical tissue mass. After birth, renal mRNA expression of NHE3, NKCC2, ROMK, NCCT, ENaC, and Na+/K+-ATPase increased relative to postnatal day 2 in wild-type mice. However, in COX-2-/- mice, a significantly lower expression was observed for NCCT, whereas NaCl/DOCA treatment significantly increased NHE3 and ROMK expression. Long-term effects of postnatal NaCl/DOCA injections indicate improved kidney function with normalization of pathologically enhanced creatinine and urea plasma levels; also, albumin excretion was observed. In summary, we present evidence that salt supplementation during the COX-2-dependent time frame of nephrogenesis partly reverses renal morphological defects in COX-2-/- mice and improves kidney function.

Use of hydroxyprogesterone caproate to prevent preterm labour in uterine didelphys: a case report.

Congenital uterine anomalies have been associated with poor reproductive outcome, which include recurrent miscarriage, abruptio placenta, intra-uterine growth restriction and preterm delivery. Here, we report a case: 36 years old, G3P2, known case of uterine didelphys, with history of preterm birth, who successfully carried her pregnancy till term with weekly intramuscular injection of 250 mg hydroxyprogesterone caproate (®Proluton Depot, Zuellig Pharma).

Characterization of endocrine features and genotype-phenotypes correlations in blepharophimosis-ptosis-epicanthus inversus syndrome type 1.

OBJECTIVE: Blepharophimosis syndrome (BPES) is an autosomal dominant genetic condition resulting from heterozygous mutations in the FOXL2 gene and clinically characterized by an eyelid malformation associated (type I) or not (type II) with premature ovarian failure. The distinction between the two forms is critical for female patients, as it may allow to predict fertility and to plan an appropriate therapy. Identifying an underlying causative mutation is not always predictive of the clinical type of BPES since genotype-phenotype correlations are not yet fully delineated. Here, we describe the clinical and hormonal phenotypes of three female patients with BPES type 1 from two novel families, correlate their phenotypes with identified mutations, and investigate the effects of hormone replacement therapy (HRT). METHODS: Clinical, biochemical, and genetic evaluation were undertaken in all the patients and genotype-phenotype correlation was analyzed. The effects of substitutive hormonal therapy on secondary sexual characteristics development and induction of menarche were evaluated. RESULTS: All patients presented with primary amenorrhea or other signs of ovarian dysfunction. Two distinct mutations, a missense p.H104R change and an in-frame p.A222_A231dup10 duplication in the FOXL2 gene were identified. Observed phenotypes were not in accordance with the prediction based on the current genotype-phenotype correlations. HRT significantly improved secondary sexual characteristics development, as well as the induction of menarche. CONCLUSIONS: This study highlights the importance of early recognition of BPES and emphasizes the need of personalized therapy and follow-up in female patients carrying distinct FOXL2 mutations.

Idiopathic partial thrombosis of the corpus cavernosum: aetiology, diagnosis and treatment.

Idiopathic partial thrombosis of the corpus cavernosum (IPT) is a rare cause of perineal pain involving thrombosis within the proximal corpora cavernosa. This article clarifies the aetiology and makes recommendations on diagnosis and treatment. Three cases are described and a systematic review of the literature is presented. Magnetic resonance imaging (MRI) scans of the penis conducted for reasons other than IPT were also reviewed, to compare the normal anatomy of the corpora cavernosa with that of IPT patients.Twenty-nine IPT cases were identified, including the three described here. All patients presented with perineal pain and in all cases the thrombus was located in the proximal part of the corpora cavernosa.IPT has been associated with haematological diseases, drugs, prior priapism, sexual activity, bicycle riding and aeroplane flights. A fibrous septum within the corporeal tissue has been identified with advanced imaging modalities. Ultrasound, computed tomography and MRI have proven useful in the diagnosis. Both surgical and medical treatments have been attempted and the results have usually been good. However, two cases of surgical treatment have resulted in erectile dysfunction. It is suggested that ITP is based on the development of penile thrombosis and/or priapism in the presence of a pre-existing fibrous septum in the corpora cavernosa. MRI should be used to confirm the presence of a thrombus and a septum. First choice of treatment is pain medication and systemic anticoagulation; more invasive treatments should only be attempted only if this approach fails.

[Menopause - facts and controversies]. / Menopauza - fakty i kontrowersje.

Menopausal period induces some hormonal changes in female organism. These alterations are responsible for many illnesses and ailments - e.g. disorders of menstrual cycle, climacteric symptoms, urine incontinence, connective tissue lesions, postmenopausal osteopenia and osteoporosis. All the changes negatively influence quality of life of women. The principal element of menopausal care in this period is hormone therapy (HT), alleviating many of the climacteric aliments. This article is focused also on some controversial topics concerning the HT action on breast, coronary system and brain.

Prevalence of WT1 mutations in a large cohort of patients with steroid-resistant and steroid-sensitive nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) represents the association of proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Steroid-resistant nephrotic syndrome (SRNS) is defined by primary resistance to standard steroid therapy. It remains one of the most intractable causes for end-stage renal disease (ESRD) in the first two decades of life. Sporadic mutations in the Wilms' tumor suppressor gene WT1 have been found to be present in patients with SRNS in association with Wilms' tumor (WT) and urinary or genital malformations, as well as in patients with isolated SRNS. METHODS: To further evaluate the incidence of WT1 mutations in patients with NS we performed mutational analysis in 115 sporadic cases of SRNS and in 110 sporadic cases of steroid-sensitive nephrotic syndrome (SSNS) as a control group. Sixty out of 115 (52%) patients with sporadic SRNS were male, 55/115 (48%) were female. Sex genotype was verified by haplotype analysis. Mutational analysis was performed by direct sequencing and by denaturing high-performance liquid chromatography (DHPLC). RESULTS: Mutations in WT1 were found in 3/60 (5%) male (sex genotype) cases and 5/55 (9%) female (sex genotype) cases of sporadic SRNS, and 0/110 (0%) sporadic cases of SSNS. One out of five female patients with mutations in WT1 developed a WT, 2/3 male patients presented with the association of urinary and genital malformations, 1/3 male patients presented with sexual reversal (female phenotype) and bilateral gonadoblastoma, and 4/5 female patients presented with isolated SRNS. CONCLUSION: According to the data acquired in this study, patients presenting with a female phenotype and SRNS and male patients presenting with genital abnormalities should especially be screened to take advantage of the important genetic information on potential Wilms' tumor risk and differential therapy. This will also help to provide more data on the phenotype/genotype correlation in this patient population.

Cefixime for the prophylaxis of urinary tract infections in children with malformative uropathies: an open study.

Urinary tract infections are often associated with urinary anomalies. An appropriate pharmacologic treatment may prevent, or may at least limit, any kidney damage due to pyelonephritis. The antibiotic prophylaxis plays a role as significant as early surgical therapy, taking into consideration also the present limitative trend for a softer therapeutic regimen. In the past few years a greater bacterial resistance has emerged against some commonly administered antibiotics. Cefixime (3rd generation cephalosporin) has been used on a wide series of patients suffering from urinary infections associated with urinary tract anomalies. A few significative results emerge from the present study. In conclusion, cefixime's effectiveness long-term prophylaxis of urinary infections associated with anomalies.