Paracrine-mediated apoptosis in reproductive tract development.
(1/210)
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)
Laparoscopically assisted full thickness skin graft for reconstruction in congenital agenesis of vagina and uterine cervix.
(2/210)
In patients with agenesis of the vagina and cervix but with a functional endometrium, the traditional treatment is hysterectomy with construction of a neovagina. We report successful treatment by laparoscopically assisted full thickness skin graft for reconstruction in a patient with congenital agenesis of the vagina and uterine cervix concomitant with haematometra and ovarian endometrioma in a 12 year old girl. Postoperatively, the vaginal skin graft healed well, and menstruation first appeared 4 weeks later. In our opinion, a combined laparoscopic and vaginal procedure with full thickness skin graft is an efficacious alternative in managing such genital defects. (+info)
Laparoscopic hemi-hysterectomy in treatment of a didelphic uterus with a hypoplastic cervix and obstructed hemivagina.
(3/210)
Maldevelopment of the Mullerian duct system may result in various urogenital anomalies including didelphic uterus with a hypoplastic cervix and obstructed hemivagina. We report a patient with this anomaly who was treated by laparoscopic hemi-hysterectomy and hysteroscopic resection of hemivagina. A 17 year old patient who had complained of vaginal pus-like discharge on and off for 1 year was diagnosed by MRI to have a double uterus with obstructed right hemivagina and ipsilateral renal agenesis. After hysteroscopic identification of hypoplasia of the right uterine cervix, laparoscopic resection of the right uterus and right Fallopian tube and hysteroscopically assisted resection of the vaginal septa were performed successfully. From our experience, combined laparoscopy and hysteroscopy may be an efficacious alternative in the management and diagnosis of Mullerian anomalies. (+info)
Laparoscopic management of a unicornuate uterus with two cavitated, non-communicating rudimentary horns: case report.
(4/210)
An 18 year old nulligravid woman presented with severe dysmenorrhoea secondary to stage IV (revised American Fertility Society) endometriosis, right haematosalpinx, right endometrioma, unicornuate uterus and two cavitated, non-communicating rudimentary uterine horns. To our knowledge, this is the first reported case of a unicornuate uterus accompanied by two rudimentary horns. Operative video-laparoscopy proved a successful approach for treating this previously unreported variant of congenital Mullerian anomaly. A review of the world literature confirms the uniqueness of this case while demonstrating laparoscopy to be a viable alternative to laparotomy for management of congenital Mullerian anomalies. The case presented may help to elucidate Mullerian duct embryology further. (+info)
Kidney-specific cadherin (cdh16) is expressed in embryonic kidney, lung, and sex ducts.
(5/210)
Cdh16 was initially described as a truncated cadherin expressed in the adult rabbit kidney. We have analyzed the expression pattern of cdh-16 during mouse embryogenesis, and show that cdh-16 transcripts are present in ureter-derived epithelia of the metanephric kidney. In addition, we demonstrate that cdh-16 is also transiently expressed in the epithelia of embryonic sex ducts and the lung of the embryo. (+info)
Targeted mutagenesis of the endogenous mouse Mis gene promoter: in vivo definition of genetic pathways of vertebrate sexual development.
(6/210)
Mutations were introduced into conserved steroidogenic factor 1 (SF1)- and SOX9-binding sites within the endogenous mouse Mullerian inhibiting substance (Mis) promoter. Male mice homozygous for the mutant SF1-binding site correctly initiated Mis transcription in fetal testes, although at significantly reduced levels. Surprisingly, sufficient MIS was produced to eliminate the MUllerian ducts. In contrast, males homozygous for the mutant SOX9-binding site did not initiate Mis transcription, resulting in pseudohermaphrodites. These studies suggest an essential role for SOX9 in the initiation of Mis transcription, whereas SF1 appears to act as a quantitative regulator of Mis transcript levels, perhaps for influencing non-Mullerian duct tissues. Comparative studies of Mis expression in vertebrates indicate that the Mis promoter receives transcriptional inputs that vary between species but result in the same functional readout. (+info)
Human ovarian cancer, cell lines, and primary ascites cells express the human Mullerian inhibiting substance (MIS) type II receptor, bind, and are responsive to MIS.
(7/210)
Six human ovarian cancer cell lines and samples of ascites cells isolated from 27 patients with stage III or IV ovarian papillary serous cystadenocarcinoma were studied individually to test whether recombinant human Mullerian inhibiting substance (rhMIS) acts via its receptor. To do these experiments, we scaled up production of rhMIS and labeled it successfully with biotin for binding studies, cloned the human MIS type II receptor for mRNA detection, and raised antibodies to an extracellular domain peptide for protein detection. These probes were first tested on the human ovarian cancer cell lines and then applied to primary ovarian ascites cells. rhMIS inhibited colony growth of five of six cell lines that expressed the human MIS type II receptor mRNA by Northern analysis while not inhibiting receptor-negative COS cells. Flow cytometry performed on MIS-sensitive ovarian cancer cell lines demonstrated specific and saturable binding of rhMIS (Kd = 10.2 nM). Ascites cells from 15 of 27 or 56% of patients tested bound biotinylated MIS (MIS-biotin) and, of the 11 that grew in soft agarose, 9 of 11 or 82% showed statistically significant inhibition of colony formation. Of the 15 patients who bound biotinylated MIS, mRNA was available for analysis from 9, and 8 of 9 expressed MIS type II receptor mRNA by reverse transcription-PCR, showing a statistically significant correlation, compared with binding, by chi2 analysis (P = 0.025). Solid ovarian cancers were positive for the MIS type II receptor protein by immunohistochemical staining, which colocalized with staining for antibody to CA-125 (OC-125). Thus, the detection of the MIS type I receptor by flow cytometry may be a useful predictor of therapeutic response to MIS and may be a modality to rapidly choose patients with late-stage ovarian cancer for treatment with MIS. (+info)
Temperature-dependent sex determination in the American alligator: AMH precedes SOX9 expression.
(8/210)
Gonadal morphogenesis is very similar among mammals, birds, and reptiles. Despite this similarity, each group utilises quite different genetic triggers for sex determination. In mammals, testis development is initiated by action of the Y-chromosome gene SRY. Current evidence suggests that SRY may act together with a related gene, SOX9, to activate another gene(s) in the pathway of testicular differentiation. A downstream candidate for regulation by SRY and SOX9 is AMH. In mouse, Sox9 is expressed in the Sertoli cells of the embryonic testis and it precedes the onset of Amh expression. During mouse gonadogenesis, Amh is confined to the embryonic testis, although it later shows postnatal expression in the ovary. Reptiles such as the American alligator, which exhibit temperature-dependent sex determination (TSD) do not have dimorphic sex chromosomes and apparently no SRY orthologue. SOX9 is expressed during testis differentiation in the alligator; however, it appears to be expressed too late to cause testis determination. Here we describe the cloning and expression of the alligator AMH gene and show that AMH expression precedes SOX9 expression during testis differentiation. This is the opposite to that observed in the mouse where SOX9 precedes AMH expression. The data presented here, as well as findings from recent expression studies in the chick, suggest that AMH expression is not regulated by SOX9 in the non-mammalian vertebrates. (+info)