Paracrine-mediated apoptosis in reproductive tract development.
In mammalian development, the signaling pathways that couple extracellular death signals with the apoptotic machinery are still poorly understood. We chose to examine Mullerian duct regression in the developing reproductive tract as a possible model of apoptosis during morphogenesis. The TGFbeta-like hormone, Mullerian inhibiting substance (MIS), initiates regression of the Mullerian duct or female reproductive tract anlagen; this event is essential for proper male sexual differentiation and occurs between embryonic days (E) 14 and 17 in the rat. Here, we show that apoptosis occurs during Mullerian duct regression in male embryos beginning at E15. Female Mullerian ducts exposed to MIS also exhibited prominent apoptosis within 13 h, which was blocked by a caspase inhibitor. In both males and females the MIS type-II receptor is expressed exclusively in the mesenchymal cell layer surrounding the duct, whereas apoptotic cells localize to the epithelium. In addition, tissue recombination experiments provide evidence that MIS does not act directly on the epithelium to induce apoptosis. Based on these data, we suggest that MIS triggers cell death by altering mesenchymal-epithelial interactions. (+info)
COUP-TF upregulates NGFI-A gene expression through an Sp1 binding site.
The formation of various tissues requires close communication between two groups of cells, epithelial and mesenchymal cells. COUP-TFs are transcription factors which have been shown to have functions in embryonic development. COUP-TFI is expressed mainly in the nervous system, and its targeted deletion leads to defects in the central and peripheral nervous systems. COUP-TFII is highly expressed in the mesenchymal component of the developing organs. A null mutation of COUP-TFII results in the malformation of the heart and blood vessels. From their expression pattern, we proposed that COUP-TFs regulate paracrine signals important for mesenchymal cell-epithelial cell interactions. In order to identify genes regulated by COUP-TF in this process, a rat urogenital mesenchymal cell line was stably transfected with a COUP-TFI expression vector. We found that NGFI-A, a gene with important functions in brain, organ, and vasculature development, has elevated mRNA and protein levels upon overexpression of COUP-TFI in these cells. A study of the promoter region of this gene identified a COUP-TF-responsive element between positions -64 and -46. Surprisingly, this region includes binding sites for members of the Sp1 family of transcription factors but no COUP-TF binding site. Mutations that abolish the Sp1 binding activity also impair the transactivation of the NGFI-A promoter by COUP-TF. Two regions of the COUP-TF molecule are shown to be important for NGFI-A activation: the DNA binding domain and the extreme C terminus of the putative ligand binding domain. The C-terminal region is likely to be important for interaction with coactivators. In fact, the coactivators p300 and steroid receptor activator 1 can enhance the transactivation of the NGFI-A promoter induced by COUP-TFI. Finally, we demonstrated that COUP-TF can directly interact with Sp1. Taken together, these results suggest that NGFI-A is a target gene for COUP-TFs and that the Sp1 family of transcription factors mediates its regulation by COUP-TFs. (+info)
Prostate development requires Sonic hedgehog expressed by the urogenital sinus epithelium.
The prostate gland develops from the urogenital sinus by a testosterone-dependent process of ductal morphogenesis. Sonic hedgehog (Shh) is expressed in the urogenital sinus epithelium and the time course of expression coincides with the formation of the main prostatic ducts. Expression is most abundant in the lumen of the urogenital sinus and in the contiguous proximal duct segments. The initial upregulation of Shh expression in the male urogenital sinus depends on the presence of testosterone. The function of Shh was examined in the male urogenital sinus which was transplanted under the renal capsule of an adult male host mouse. Blockade of Shh function by a neutralizing antibody interferes with Shh signaling and abrogates growth and ductal morphogenesis in the transplanted tissue. These observations show that testosterone-dependent Shh expression in the urogenital sinus is necessary for the initiation of prostate development. (+info)
Studies of the specificity of ureaplasmas for marmosets.
Marmosets, from which endogenous ureaplasmas had been eradicated by treatment with minocycline, were tested for susceptibility to infection by ureaplasmas from the genital and respiratory tracts of other animal species. They could be infected with ureaplasmas of human and simian origin, but were resistant to bovine and canine ureaplasmas. The results indicated that human, marmoset and squirrel-monkey ureaplasmas may form a biological subgroup, distinct from bovine and canine ureaplasmas, and that host range should not be ignored as a parameter for classification. (+info)
Comparative developmental aspects of selected organ systems. II. Gastrointestinal and urogenital systems.
A brief description of the basic patterns of mammalian organogenesis of the gastrointestinal and urogenital systems is presented based on events as they occur in human beings. The emphasis is not on the details of this development, but rather on its organization and timing, with tables of comparative development providing a comparison of similar events in man, rat, mouse, and chick. (+info)
Antibody responses in the lower respiratory tract and male urogenital tract in humans after nasal and oral vaccination with cholera toxin B subunit.
Nasal vaccine delivery is superior to oral delivery in inducing specific immunoglobulin A (IgA) and IgG antibody responses in the upper respiratory tract. Although an antibody response in the nasal passages is important in protecting against primary colonization with lung pathogens, antibodies in the lungs are usually required as well. We immunized 15 male volunteers twice nasally or orally with cholera toxin B subunit (CTB) and determined the specific antibody levels in serum, bronchoalveolar lavage (BAL) fluid, and urine before and 2 weeks after immunization. Nasal immunization induced fivefold increases in the levels of specific IgA antibodies in BAL fluid of most volunteers, whereas there were no significant specific IgA responses after oral immunization. The specific IgG antibody level increased eightfold in BAL fluid in the nasally vaccinated subjects, and the major part of IgG had most probably been transferred from serum. Since the specific IgG response in serum was lower in the individuals vaccinated orally, the IgG response in BAL fluid in this group was also lower and not significant. In conclusion, nasal immunization is also preferable to the oral route when vaccinating against lower respiratory tract infections, and a systemic immune response is considerably more important in the lower than in the upper respiratory tract. Moreover, both nasal and oral immunizations were able to stimulate 6- to 10-fold specific IgA and IgG responses in urine in about half of the individuals, which indicates that distant mucosal vaccination might be used to prevent adhesion of pathogens to the urogenital tract. (+info)
Distinct but overlapping expression patterns of two vertebrate slit homologs implies functional roles in CNS development and organogenesis.
The Drosophila slit gene (sli) encodes a secreted leucine-rich repeat-containing protein (slit) expressed by the midline glial cells and required for normal neural development. A putative human sli homolog, SLIT1, has previously been identified by EST database scanning. We have isolated a second human sli homolog, SLIT2, and its murine homolog Slit2. Both SLIT1 and SLIT2 proteins show approximately 40% amino acid identity to slit and 60% identity to each other. In mice, both genes are expressed during CNS development in the floor plate, roof plate and developing motor neurons. As floor plate represents the vertebrate equivalent to the midline glial cells, we predict a conservation of function for these vertebrate homologs. Each gene shows additional but distinct sites of expression outside the CNS suggesting a variety of functions for these proteins. (+info)
Evaluation of the Etest for susceptibility testing of Mycoplasma hominis and Ureaplasma urealyticum.
The Etest was used for antibiotic susceptibility testing of Mycoplasma hominis and Ureaplasma urealyticum isolates and the results were compared with those obtained with the broth microdilution method. For 50 clinical isolates of M. hominis the MICs of doxycycline, ofloxacin and ciprofloxacin agreed within +/- one dilution and +/- two dilutions in 82-98% and 98-100% of cases, respectively. The MICs of erythromycin, azithromycin, doxycycline, ofloxacin and ciprofloxacin were evaluated for 50 clinical isolates of U. urealyticum. The corresponding levels of agreement were 70-98% and 94-100%, respectively. Reference isolates M. hominis PG-21 and U. urealyticum T-960 were also used. The Etest seems to be an alternative method for determination of MICs of antibiotics with M. hominis and U. urealyticum. (+info)