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P Parma

Publications and source records attributed to P Parma.

17 recordsLinked to original sources

Time course of female-to-male sex reversal in 38,XX fetal and postnatal pigs.

In an attempt to understand the etiology of intersexuality in pigs, we thoroughly analyzed the gonads of 38,XX (SRY negative) female to male sex-reversed animals at different developmental stages: during fetal life [50 and 70 days postcoitum (dpc)], just after birth [35 days postpartum (dpp)] and during adulthood. For each animal studied, we performed parallel histological and ultrastructural analyses on one gonad and RT-PCR analysis on the other gonad in order to define the expression profiles of sexually regulated genes: SOX9, 3beta-HSD, P450 aromatase, AMH, FOXL2, and Wnt4. Light and electron microscopic examination showed that testicular cords differentiated in XX sex-reversed gonads but were hypoplastic. Although the testicular cords contained gonia at the fetal stages, the germ cells had all died through apoptosis within a few weeks after birth. Ultrastructurally normal Leydig cells also differentiated, but later, and enclosed whorl-like residual bodies. At the fetal stages, three of the six genes studied in the intersex gonads presented, as early as 50 dpc, a modified expression profile corresponding to an elevated expression of SOX9 and the beginning of AMH and P450 aromatase gene transcription. In addition to genes involved in the testicular pathway, the same gonads expressed FOXL2, an ovarian-specific factor. The ovaries of true hermaphrodites were ineffective in ensuring correct folliculogenesis and presented abnormal expression profiles of ovarian specific genes after birth. These results indicate that the genes involved in this pathology act very early during gonadogenesis and affect the ovary-differentiating pathway with variable expressivity from ovarian germ cell depletion through to trans-differentiation into testicular structures.

Animals↗

Reverse transcription-polymerase chain reaction analysis of genes involved in gonadal differentiation in pigs.

In mammals, testis development is initiated in the embryo as a response to the expression of the sex-determining gene, SRY. The time course of SRY expression during gonadal differentiation in the male has been described in detail only in mice and sheep. In this study, we used reverse transcription-polymerase chain reaction analysis to define the SRY transcription profile in pig genital ridges. SRY transcripts were first detectable from 23 days postcoitum (dpc), then declined sharply after 35 dpc. None were detected at 60 dpc. In addition, we analyzed temporal expression of other genes known to be involved in mammalian sex determination: WT-1, SF-1, SOX9, and AMH. A key stage seems to be 28 dpc, in which SOX9 expression switches between the male and female, and AMH expression begins to attest to Sertoli cell differentiation and to correspond to seminiferous cord formation in the male. Expression of gonadotropin receptors and aromatase was also investigated in porcine gonads, and we showed that their transcripts were detected very early on, especially in the male: 25 dpc for the LH receptor (rLH) and aromatase, and 28 dpc for the FSH receptor (rFSH). In the female, aromatase transcripts were not detected until 70 dpc, and rFSH expression occurred later: at 45 dpc at the onset of meiosis. Moreover, no difference was observed between the sexes for the onset of rLH transcription at 25 dpc. Such a thorough study has never been performed on pigs; developmental analysis will be useful for investigating sex-reversed gonads and determining ontogeny in intersexuality, a common pathology in pigs.

Animals↗

A synthetic, nitrogenated antimetastatic and anti-angiogenic compound with low toxicity in vivo.

The design of more effective therapies for metastatic disease involves development of new compounds able to specifically block the malignant process. We demonstrated previously that a new synthetic nitrogenated compound 3'-1-chloroethyl-2,3-dihydro-1H-imidazo-(2, 1-i)-purine-4-ium-7-yl-3'-deoxy-1',5', 6'-tri-O-(methylsulfonyl)-muco-inositol chloride (DIC) had an anti-proliferative activity on tumor cells in vitro. In the present work we demonstrate that DIC induces apoptosis on the LM3 murine mammary adenocarcinoma cell line in vitro and has anti-angiogenic activity in vivo. We also evaluated toxicity, biodistribution and anti-neoplastic properties of DIC in vivo. Toxicity studies allowed us to establish the LD50 (750 mg/kg body weight). Administration of 250 mg/kg/day (LD10) for 6 days did not cause overt toxic effects. Biodistribution assays revealed that DIC was rapidly eliminated (60% at t=10 min), although it accumulated in tumor tissue at higher concentrations than in other tissues. Daily s.c. treatment with DIC (LD10) for 24 days significantly reduced the number of spontaneous lung metastases. These results suggest that DIC has the ability of impairing the metastatic development by inhibiting angiogenesis and inducing apoptosis on tumor cells.

Adenocarcinoma↗

[Interstitial cystitis: epidemiology].

The epidemiological assessment of intestitial cystitis (IC) is not definitive as no diagnostic criteria, such as endoscopy or biochemical and anatomopathological examination, exist. The diagnosis is solely based on symptoms like urgency, frequency and pelvic pain. The first studies on the population date back from 20 years ago and show a percentage of 10 cases every 100 thousand inhabitants. There is weak link between genetic factors, immunological diseases, previous cystitis or eating habits and intestitial cystitis. Epidemiological studies have highlight the frequency of this disease, and stressed the importance of stricted behavioural rules for the first stages of intestitial cystitis.

Cystitis, Interstitial↗

[Interstitial cystitis: surgical treatment].

Surgical therapy of interstitial cystitis must never be considered a first option but must be reserved for cases, less than 10%, in which conservative therapy has proven ineffectual. Surgical therapy includes a variety that started at the turn of the century. Neurosurgical denervation and perivesical denervation like cysto-cystoplasty and cystolysis, manipulate the innervation to reduce the bladder's hypersensitivity. This surgical approach may be considered in patients in whom bladder capacity is normal. The results are uncertain and the complications like neurogenic bladder relevant. Enterocystoplasty is much more widespread because interstitial cystitis is a benign disease that rarely required radical surgery. Augmentation cystoplasty and substitution cystoplasty are two variants but only the later has a rationale as it involves the resection of the detrusor which is the source of the pain. Detubularization drastically reduced urinary incontinence. The resection of the detrusor can be supratrigonal, subtrigonal or at the proximal urethra like in the orthotopic neobladder. If urinary diversion is chosen, the bladder must be removed. Before recommending surgical therapy each patient should undergo tests for the localization of the pain; moreover psychological and gynaecological evaluations should be made. If the bladder capacity exceeds 400 cc surgical operation is not advisable. If, on the other hand, the bladder capacity is lower than 400 cc substitution cystoplasty is first choice. If the patient suffers from trigonal cystitis or urethral hypersensitivity, urinary diversion is a better therapy. According to the questionnaires send to the Urologic Departments in Lombardy in 1998, the most widespread type of operation seems to be supratrigonal cystectomy + enterocystoplasty and augmentation cystoplasty. Subtrigonal cystectomy or urinary diversion are only occasionally chosen; continent pouch is the least frequent therapy at all.

Adult↗

Porcine Dax-1 gene: isolation and expression during gonadal development.

The identification of XY females carrying a duplication of a region of the X chromosome (Xp21) led to the hypothesis that a double dose of a gene in the duplicated region causes sex reversal (DSS; dosage sensitive sex reversal). A gene isolated from this region, named DAX-1 (DSS-AHC critical region on the X), encodes a new member of the nuclear hormone receptor family. Here, we describe the isolation of porcine Dax-1 and the analysis of its pattern of expression both during foetal development and in several adult tissues. Dax-1 is expressed in the adrenals, the pituitary gland and the gonads at various stages of differentiation. In gonads, Dax-1 expression starts between 21 and 23 days post coitum in both XX and XY urogenital ridges then continues to be expressed until adult age. The expression in these tissues indicates the involvement of DAX-1 in the development and the function of the reproductive system at multiple levels.

Amino Acid Sequence↗

Mapping in pig of genes involved in sexual differentiation: AMH, WT1, FTZF1, SOX2, SOX9, AHC, and placental and embryonic CYP19.

Intersexuality has been reported in pigs and investigations are in progress to identify and physically map the genes involved in sex-reversal. In this study we have mapped on porcine chromosomes seven genes which might be implicated in this developmental pathway. Four genes were mapped by radioactive in situ hybridization: AMH (Anti-Müllerian Hormone) and WT1 (Wilms' Tumor gene 1) were both mapped to pig chromosome 2 (SSC2) in the q14-->q21 and p14-->q11 regions, placental CYP19 (cytochrome P450, subfamily XIX) and FTZF1 (fushi tarazu factor [Drosophila] homolog 1, alias SF1 [steroidogenic factor 1]) to pig chromosome 1 (SSC1) in the q14-->q17 and q210-->q211 regions respectively. Four other genes were regionally located by PCR analysis on a cytogenetically characterized porcine somatic cell hybrid panel: a second CYP19 gene (expressed in embryo) was mapped to porcine 1q12-->q17, AHC (alias DAX1, adrenal hypoplasia congenital) to porcine Xp24, SOX2 and SOX9 (SRY sex determining region Y-box 2 and 9) to 13q23-->q41 and 12p13-->p11 respectively. These results are in global agreement with mapping data available in other mammalian species.

Animals↗

Molecular analysis of an XY mare with gonadal dysgenesis.

In this study, cytogenetic analysis of an infertile mare revealed a 64, XY karyotype. The XY sex-reversed animal had a female phenotype with gonadal dysgenesis. Using Southern blot analysis, we tested for the presence of two Y-specific genes SRY and ZFY by using DNA isolated from peripheral blood leukocytes. The results showed that at least the DNA-binding domain of the SRY gene was deleted from the Y chromosome of the XY mare but that the ZFY gene was present on this chromosome.

Animals↗

Genetic analysis of 38XX males with genital ambiguities and true hermaphrodites in pigs.

In pig, the frequency of intersexuality ranges from 0.1 to 0.6%, depending on the breed. In a closed pig herd at INRA an intersex condition was observed in 0.75% of 'females'. The present study describes 11 animals with a 38XX karyotype and the presence of testicular tissue. Phenotypically, all presented with abnormal external or/and internal genitalia. Southern blot analysis with Y-specific probes (SRY and ZFY) revealed the absence of Y material in all animals tested. By polymerase chain reaction (PCR) amplification, 10 of 11 intersex pigs lacked the SRY gene in gonad DNA. These data are compatible with an autosomally (or pseudoautosomally) determined mechanism. Moreover, analysis of familial cases seemed to indicate that 38XX male pseudohermaphrodites and 38XX true hermaphrodites may represent alternative manifestations of the same genetic defect.

Animals↗

[Features of diabetic angiopathy: impotence].

Erectile dysfunction occurs more frequently in the diabetic population than in the general population. This article analyzes a review of this pathology, its prevalence and incidence in the diabetic population, its multifactor origin, and how these causes interact with each other and the therapy required.

Diabetic Angiopathies↗