RESUMO
INTRODUCTION: One of the transitional zones of the human body is situated in the cervix uteri. The developmental differentiation of epithelial and stromal characteristics in such a region is of high clinical interest. However, few studies have focused on the development of this region, and information in anatomical and clinical textbooks is limited. We therefore examined the development of the human vaginal fornix and the cervix uteri during prenatal development. MATERIALS AND METHODS: We examined 29 female embryos and fetuses between 20 and 34 weeks and two newborns using histology and immunohistochemistry. RESULTS: The characteristic shape of the portiocervicis and the vaginal fornix first became visible in mid-term fetuses because of the different muscular coats and of an uncategorized Müllerian-derived epithelium, which was rapidly replaced by a multilayered squamous epithelium. Only thereafter, in older fetuses, were there organogenetic differentiation of the epithelia and the underlying stroma of the cervical canal. UGS-derived p63/CK17-positive cells could be identified as precursor cells for the squamous epithelium, and Müllerian-derived CK7-positive cells for the columnar-type epithelium. Both cell types and different stromal zones were already present in a prenatal transformation zone. Initial functional differentiation could be observed in perinatal stages. CONCLUSIONS: Our results on prenatal human development strongly support the view that two different cell lineages meet at the transitional zone of the cervix uteri and that these lineages depend on alternative signals from the underlying stromal compartment.
Assuntos
Colo do Útero/embriologia , Vagina/embriologia , Diferenciação Celular , Células Epiteliais , Feminino , Feto , Humanos , Recém-NascidoRESUMO
Congenital anomalies of the female reproductive tract that present with primary amenorrhea involve Müllerian aplasia, also known as Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS), and cervical and vaginal anomalies that completely obstruct the reproductive tract. Karyotype abnormalities do not exclude the diagnosis of MRKHS. Familial cases of Müllerian anomalies and associated malformations of the urinary and skeletal systems strongly suggest a complex genetic etiology, but so far, the molecular mechanism in the vast majority of cases remains unknown. Primary amenorrhea may also be the first presentation of complete androgen insensitivity syndrome, steroid 5α-reductase type 2 deficiency, 17ß-hydroxysteroid dehydrogenase type 3 deficiency, and Leydig cells hypoplasia type 1; therefore, these disorders should be considered in the differential diagnosis of the congenital absence of the uterus and vagina. The molecular diagnosis in the majority of these cases can be established.
Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/patologia , Amenorreia/genética , Amenorreia/patologia , Colo do Útero/anormalidades , Anormalidades Congênitas/patologia , Ductos Paramesonéfricos/anormalidades , Vagina/anormalidades , 17-Hidroxiesteroide Desidrogenases/deficiência , 17-Hidroxiesteroide Desidrogenases/genética , Síndrome de Resistência a Andrógenos/genética , Síndrome de Resistência a Andrógenos/patologia , Colo do Útero/embriologia , Colestenona 5 alfa-Redutase/deficiência , Colestenona 5 alfa-Redutase/genética , Anormalidades Congênitas/diagnóstico , Transtorno 46,XY do Desenvolvimento Sexual/genética , Transtorno 46,XY do Desenvolvimento Sexual/patologia , Feminino , Humanos , Masculino , Ductos Paramesonéfricos/patologia , Testículo/anormalidades , Testículo/patologia , Vagina/embriologiaRESUMO
The fetus is exposed to high plasma concentrations of unbound estrogens and progesterone throughout pregnancy. However, secretory or decidual changes in the fetal uterus occur relatively infrequently before birth, suggesting a variable endometrial progesterone response at the time of birth. Arguably, partial progesterone resistance that persists into adolescent years may compromise the physiological transformation of the spiral arteries and predispose for defective placentation in the case of pregnancy. Decidualization of the endometrial stromal compartment and junctional zone myometrium precedes trophoblast invasion. It represents the first step in the process of spiral artery remodeling needed to establish effective uteroplacental blood flow by midpregnancy. The major obstetric syndromes caused by impaired placental bed spiral artery remodeling are prevalent in teenage pregnancies, including preeclampsia, fetal growth restriction, and spontaneous preterm labor. Preconditioning of the uterus in response to cyclic menstruation during adolescence may be critical to achieve full uterine responsiveness to hormonal cues. Understanding the mechanisms of functional maturation of the uterus during the early reproductive years may yield novel insights into the major obstetric syndromes.
Assuntos
Endométrio/anormalidades , Número de Gestações , Doenças Placentárias/etiologia , Complicações na Gravidez/etiologia , Gravidez na Adolescência , Doenças Uterinas/embriologia , Útero/embriologia , Adolescente , Colo do Útero/embriologia , Endométrio/embriologia , Feminino , Retardo do Crescimento Fetal/etiologia , Humanos , Recém-Nascido , Trabalho de Parto Prematuro/etiologia , Pré-Eclâmpsia/etiologia , Gravidez , Doenças Uterinas/complicaçõesRESUMO
Using general histological and immunohistochemical methods, the sources of "reserve cells" of the epithelial lining of the uterus and vagina were studied on the material obtained from human embryos and fetuses. From 13th to 20th week of fetal development, the epithelial lining of the cervix was formed with the participation of the urogenital sinus (UGS). The cells of the latter interacted with the coelomic epithelial cells of the paramesonephric ducts (PMD). After 25th week, UGS cells were dispersed along the length of the cervix, lying on the basement membrane beneath the columnar epithelial cells. It is suggested that epitheliocytes of UGS are the source of the "reserve cells". Taking into account the tissue nature of the "reserve cell" it is expedient to determine them as mesonephroblasts. Cells are present in the cervical epithelium as a concomitant determined cellular differon.
Assuntos
Colo do Útero , Epitélio/embriologia , Desenvolvimento Fetal/fisiologia , Feto , Idade Gestacional , Colo do Útero/citologia , Colo do Útero/embriologia , Células Epiteliais/citologia , Feminino , Feto/citologia , Feto/embriologia , HumanosRESUMO
BACKGROUND: Our previous work provided evidence that early cervical cancer is locally confined to the Müllerian compartment that develops in women from the embryonic paramesonephric-mesonephric complex. We aimed to investigate if the concept of tumour permeation within ontogenetic domains is also valid for tumour progression and advanced disease. METHODS: Starting from Carnegie stage 13, four successive steps in the organogenesis of the human uterine cervix were defined and an ontogenetic staging system for cervical cancer based on organ development was described. Histopathological and clinical data of patients with cervical cancer FIGO stages IB-IVA were raised prospectively from Oct 16, 1999, until Dec 20, 2012, and from March 8, 2000, until April 4, 2013, for two surgical trials of ontogenetic compartment resection without adjuvant radiation at the University of Leipzig (total or extended mesometrial resection [TMMR or EMMR]; and [laterally] extended endopelvic resection [LEER]). The primary endpoints of these trials were pathological resection state and locoregional tumour control. Patients who underwent TMMR and EMMR had follow-up assessment every 3-6 months for 5 years, and yearly thereafter. Patients who had (L)EER, every 3-6 months for 10 years, and yearly thereafter. By analysing the presence of disease within the classified tissues and disease outcome in these patients, and by examining relapse patterns, we were able to observe whether surgical excision within developmental compartments was sufficient for disease control. Survival curves were compared using the log-rank test. The effect of ontogenetic tumour stage and pathological tumour stage on overall survival was assessed by Cox proportional hazard models. The trials are registered as an ongoing observational monocentric study at the University of Leipzig Cancer Centre (ULCC012-13-28012013). FINDINGS: 367 patients were included in our analysis. Staged organogenesis of the uterine cervix and progressive local growth of cervical carcinoma occur in the same tissue domains. The neoplasm originating in the uterine cervix, ontogenetic tumour stage 1 (oT1, n=217), permeates successively during its malignant progression the tissues developed from the Müllerian compartment (oT2, n=101), the genital metacompartment (oT3, n=38), and the urogenitorectal metacompartment (oT4, n=11). Ontogenetic staging, when comparing patients with oT1 and oT2 disease to those with oT3 and oT4 disease (hazard ratio 5·9, 95% CI 2·2-15·5; p=0·00036) was a better prognostic indicator for survival than pathological staging when comparing pT1b and pT2a with pT2b and pT4 disease (2·0, 95% CI 0·7-5·5; p=0·170). Resection of the stage-related ontogenetically specified tissue domains and their associated regional lymphoid tissues achieved an R0 resection in 363 (99%) of 367 patients and locoregional tumour control at 5 years was 94% (95% CI 92-97). 13 patients had grade 3 or 4 adverse events, the majority of which were urinary (10, 77%). INTERPRETATION: Cervical cancer infiltrates the adult tissues established during ontogeny, pursuing the developmental steps in retrograde sequence. Clinical translation of these insights into ontogenetic tumour staging and compartment resection holds the potential to improve prognostic assessment and curative treatment. FUNDING: University of Leipzig and Leipzig School of Radical Pelvic Surgery.
Assuntos
Colo do Útero/embriologia , Colo do Útero/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias do Colo do Útero/patologia , Colo do Útero/cirurgia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Alemanha , Humanos , Histerectomia , Estimativa de Kaplan-Meier , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Organogênese , Modelos de Riscos Proporcionais , Estudos Prospectivos , Radioterapia Adjuvante , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/cirurgiaRESUMO
The cervical squamocolumnar (SC) junction is the site of a recently discovered 'embryonic' cell population that was proposed as the cell of origin for cervical cancer and its precursors. How this population participates in cervical remodelling and neoplasia is unclear. In the present study, we analysed the SC junction immunophenotype during pre- and post-natal human and mouse development and in the adult, processes of metaplastic evolution of the SC junction, microglandular change, and early cervical neoplasia. Early in life, embryonic cervical epithelial cells were seen throughout the cervix and subsequently diminished in number to become concentrated at the SC junction in the adult. In all settings, there was a repetitive scenario in which cuboidal embryonic/SC junction cells gave rise to subjacent metaplastic basal/reserve cells with a switch from the SC junction positive to negative immunophenotype. This downward or basal (rather than upward or apical) evolution from progenitor cell to metaplastic progeny was termed reverse or 'top down' differentiation. A similar pattern was noted in high-grade squamous intraepithelial lesions (HSILs), suggesting that HPV infection of the cuboidal SC junction cells initiated outgrowth of basally-oriented neoplastic progeny. The progressive loss of the embryonic/SC junction markers occurred with 'top down' differentiation during development, remodelling, and early neoplasia. Interestingly, most low-grade SILs were SC junction-negative, implying infection of metaplastic progeny rather than the original SC junction cells. This proposed model of 'top down' differentiation resolves the mystery of how SC junction cells both remodel the cervix and participate in neoplasia and provides for a second population of metaplastic progeny (including basal and reserve cells), the infection of which is paradoxically less likely to produce a biologically aggressive precursor. It also provides new targets in animal models to determine why the SC junction is uniquely susceptible to carcinogenic HPV infection.
Assuntos
Células-Tronco Neoplásicas/patologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Alphapapillomavirus/isolamento & purificação , Alphapapillomavirus/patogenicidade , Animais , Diferenciação Celular , Colo do Útero/embriologia , Colo do Útero/imunologia , Colo do Útero/patologia , Modelos Animais de Doenças , Células-Tronco Embrionárias/patologia , Epitélio/imunologia , Epitélio/patologia , Epitélio/virologia , Feminino , Humanos , Metaplasia , Camundongos , Camundongos Endogâmicos BALB C , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/virologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/patologia , Displasia do Colo do Útero/imunologia , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/virologiaRESUMO
OBJECTIVE: Studies on the development of the embryological and fetal development of the cervix and the vagina are rare and mostly go back to the first decades of the last century. The aims of this review were to present the latest knowledge concerning the developmental origin of cervical and vaginal epithelium and to point out new results in the context of different clinical findings. MATERIALS AND METHODS: Relevant studies published between 1910 and 2013 were identified via PubMed, MEDLINE, OVID, Web of Science, and EMBASE. The reference lists of retrieved articles were reviewed to locate additional articles. Each abstract was reviewed, and the appropriate publications were obtained and reviewed as well. A total of 33 articles and 8 book chapters were selected for citation in this review. RESULTS: New objective findings clearly show that human prenatal epithelialization of the cervix and vagina results in 3 morphogenetically determined units: (i) the Müllerian columnar epithelium of the endocervix, (ii) the Müllerian squamous epithelium of the ectocervix and the upper vagina, and (iii) the vaginal squamous epithelium of the lower vagina. CONCLUSIONS: These results are of high clinical relevance and may provide new insight into the histogenesis of ectopy, vaginal adenosis, and the congenital transformation zone. They should be added to the explanations in gynecological, colposcopical, and gynecopathological textbooks.
Assuntos
Colo do Útero/embriologia , Colo do Útero/crescimento & desenvolvimento , Epitélio/embriologia , Epitélio/crescimento & desenvolvimento , Vagina/embriologia , Vagina/crescimento & desenvolvimento , Feminino , HumanosRESUMO
AIM: Minimal data are available on the role of pelvic exenteration in patients with recurrent squamous cell carcinoma (SCC) of the pelvic organs. This study aimed to highlight our experience of pelvic exenteration in patients with recurrent and re-recurrent SCC of the pelvic organs. METHOD: A retrospective review of all patients who underwent pelvic exenteration for recurrent SCC of the pelvic organs arising from the embryological cloaca from 1994 to 2010 was performed. RESULTS: Twenty-four patients (median age 59, range, 27-79 years) underwent pelvic exenteration for recurrent SCC of the anus (18), cervix and upper vagina (2), lower vagina (1) and the vulva (3). Nine patients with anal SCC had undergone abdominoperineal excision prior to pelvic exenteration. Ten (41.7%) patients underwent a complete pelvic exenteration procedure, while sacrectomy was performed in 13 (54.2%) patients. There was no 30-day inpatient mortality. An R0 resection was achieved in 15 (62.5%) patients. Three (12.5%) had R1 resections while 6 (25%) had R2 resections. In the 15 patients with an R0 resection, 7 (46.7%) developed metastatic disease at a median of 18 (range 10-131) months. After a median follow-up of 26 (range 4-169) months, 1- and 2-year overall survival rates were 64% [95% confidence interval (CI), 44-84%] and 57% (95% CI 35-79%), respectively. CONCLUSION: Pelvic exenteration for recurrent SCC of the cloaca is safe and feasible even after previous salvage surgery. An R0 resection can be achieved in 62.5% of the patients with reasonable early survival though less than published recurrent rectal cancer studies.
Assuntos
Neoplasias do Ânus/cirurgia , Carcinoma de Células Escamosas/cirurgia , Neoplasias dos Genitais Femininos/cirurgia , Recidiva Local de Neoplasia/cirurgia , Exenteração Pélvica , Adulto , Idoso , Canal Anal/embriologia , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/secundário , Colo do Útero/embriologia , Feminino , Neoplasias dos Genitais Femininos/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Vagina/embriologia , Neoplasias Vaginais/patologia , Neoplasias Vaginais/cirurgia , Vulva/embriologia , Neoplasias Vulvares/patologia , Neoplasias Vulvares/cirurgiaRESUMO
In mammals, the female reproductive tract (FRT) develops from a pair of paramesonephric or Müllerian ducts (MDs), which arise from coelomic epithelial cells of mesodermal origin. During development, the MDs undergo a dynamic morphogenetic transformation from simple tubes consisting of homogeneous epithelium and surrounding mesenchyme into several distinct organs namely the oviduct, uterus, cervix and vagina. Following the formation of anatomically distinctive organs, the uniform MD epithelium (MDE) differentiates into diverse epithelial cell types with unique morphology and functions in each organ. Classic tissue recombination studies, in which the epithelium and mesenchyme isolated from the newborn mouse FRT were recombined, have established that the organ specific epithelial cell fate of MDE is dictated by the underlying mesenchyme. The tissue recombination studies have also demonstrated that there is a narrow developmental window for the epithelial cell fate determination in MD-derived organs. Accordingly, the developmental plasticity of epithelial cells is mostly lost in mature FRT. If the signaling that controls epithelial differentiation is disrupted at the critical developmental stage, the cell fate of MD-derived epithelial tissues will be permanently altered and can result in epithelial lesions in adult life. A disruption of signaling that maintains epithelial cell fate can also cause epithelial lesions in the FRT. In this review, the pathogenesis of cervical/vaginal adenoses and uterine squamous metaplasia is discussed as examples of such incidences.
Assuntos
Diferenciação Celular , Células Epiteliais/citologia , Ductos Paramesonéfricos/citologia , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/patologia , Animais , Colo do Útero/anormalidades , Colo do Útero/citologia , Colo do Útero/embriologia , Dietilestilbestrol/efeitos adversos , Células Epiteliais/metabolismo , Estrogênios não Esteroides/efeitos adversos , Feminino , Humanos , Mesoderma/citologia , Mesoderma/metabolismo , Metaplasia , Ductos Paramesonéfricos/embriologia , Ductos Paramesonéfricos/metabolismo , Organogênese , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologia , Útero/citologia , Útero/embriologia , Vagina/anormalidades , Vagina/citologia , Vagina/embriologiaRESUMO
PURPOSE OF REVIEW: Cervical agenesis is an extremely rare congenital anomaly of the female reproductive tract. There are many anatomical forms that constitute this type of cervical abnormality and the literature is replete with attempts to surgically restore a patent outflow tract and preserve fertility in these patients. There are no carefully designed cohort or randomized trials to support a best surgical practice; past reports are descriptive only. RECENT FINDINGS: Of late, there has been renewed interest in the surgical treatment of cervical dysgenesis with techniques both through laparotomy with hysterotomy and more recently, minimally invasive approaches, which have attempted to restore a patent outflow tract without perineal dissection or graft harvesting in an attempt to avoid uterovaginal scarring if further surgery is necessary. To maintain consistency in the field of surgical reconstruction of the female reproductive tract, there has been a call for streamlined classifications of the anatomical abnormalities observed to better compare patient findings and the outcome of their surgical reconstruction in the literature. SUMMARY: The authors discuss the embryological development of this rare reproductive tract abnormality and have proposed a systematic surgical strategy for each anatomic finding. Ultimately, counseling patients on the best surgical approach requires a discussion on the potential postoperative complications, the degree of cervical abnormality, and the patient's desired treatment outcome. Whether the patient desires definitive treatment with a hysterectomy to avoid the risk of further surgery or, when anatomically appropriate, she wants to pursue a patent outflow tract and the possibility of future childbearing, evidence-based medicine must become the source for surgical strategies.
Assuntos
Colo do Útero/anormalidades , Colo do Útero/cirurgia , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/cirurgia , Colo do Útero/embriologia , Feminino , Humanos , Vagina/anormalidades , Vagina/cirurgiaRESUMO
BACKGROUND: The existence of a longitudinal vaginal septum with double cervix communicating bilaterally with a nonseptate uterine body and normal adnexa is an unusual müllerian anomaly. CASE: A 43-year-old woman presented with menorrhagia and duplication of the cervix and vagina. Afibromatous uterus was suggested by clinical examination and confirmed by ultrasonography. The patient underwent total abdominal hysterectomy with bilateral salpingooophorectomy. The surgical specimen revealed a fibromatous uterus with double cervix communicating bilaterally with a nonseptate uterine body; both adnexa were normal. CONCLUSION: This rare müllerian anomaly is inconsistent with the classical embryologic theory of caudal to cranial müllerian development but supports the alternative embryologic hypothesis suggested by Müller et al, according to which fusion and absorption begin at the isthmus and proceed simultaneously in both the cranial and caudal directions.
Assuntos
Colo do Útero/anormalidades , Ductos Paramesonéfricos/anormalidades , Útero/anormalidades , Vagina/anormalidades , Adulto , Colo do Útero/embriologia , Colo do Útero/cirurgia , Feminino , Humanos , Histerectomia , Ductos Paramesonéfricos/embriologia , Ductos Paramesonéfricos/cirurgia , Ovariectomia , Útero/embriologia , Útero/cirurgia , Vagina/embriologia , Vagina/cirurgiaRESUMO
Ghrelin, the endogenous ligand of the GH secretagogue receptor (GHS-R), is a newly identified, ubiquitously expressed molecule that has been involved in a wide array of endocrine and nonendocrine functions, including cell proliferation. In this context, our group recently reported the expression of ghrelin and its functional receptor, the GHS-R type 1a, in the human ovary and testis as well as several testicular tumors. Ovarian malignancies, however, remain unexplored. Notably, a vast majority of ovarian tumors derive from the surface epithelium, which originates from the celomic epithelium. Considering the proven expression of ghrelin in the human ovary, and its reported effects in the proliferative activity of different cancer cell lines, we aimed at evaluating whether the ovarian surface epithelium as well as related reproductive structures and tumors are potential targets of ghrelin. To this end, expression of GHS-R1a was analyzed by immunohistochemistry in a panel of normal, metaplastic, and neoplastic tissues. Uniform GHS-R1a immunostaining was detected throughout the ovarian surface epithelium. Likewise, ciliated cells within the fallopian tube epithelium showed strong GHS-R1a expression. In contrast, other celomic derivatives, such as endometrium and endocervix, were negative for GHS-R1a immunoreactivity. In keeping with data from normal tissues, inclusion cysts from the surface epithelium expressed GHS-R1a. Similarly, benign serous tumors resembling fallopian tube epithelium were also positive, whereas serous cystadenocarcinomas showed GHS-R1a expression only in highly differentiated specimens. In contrast, other neoplasms, such as mucinous cystadenomas and cystadenocarcinomas, endometrioid tumors, clear cell carcinomas, and Brenner tumors, did not express GHS-R1a. In conclusion, our results demonstrate that the ovarian surface epithelium and related tumors are potential targets for systemic or locally produced ghrelin because they express the functional type 1a GHS-R. Considering the relevant role of the ovarian surface epithelium in key physiological events (such as ovulation) and neoplastic transformation of the ovary, the potential actions of ghrelin in those phenomena merit further investigation.
Assuntos
Tubas Uterinas/metabolismo , Neoplasias Ovarianas/metabolismo , Ovário/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Colo do Útero/embriologia , Colo do Útero/metabolismo , Endométrio/embriologia , Endométrio/metabolismo , Células Epiteliais/metabolismo , Tubas Uterinas/embriologia , Feminino , Humanos , Imuno-Histoquímica , Ductos Paramesonéfricos/embriologia , Neoplasias Ovarianas/patologia , Ovário/embriologia , Receptores de GrelinaRESUMO
BACKGROUND: Ciliation is a normal finding in the endometrium, fallopian tubes and cervix. Because cilia are characteristically lost when malignant tumors arise at these sites, the detection of cilia on light microscopy is frequently used to support a benign diagnosis. Ciliated carcinomas of müllerian duct origin, however, do occur, albeit rarely, and can pose a potential diagnostic difficulty in cytologic specimens. CASE: A woman with a histologically confirmed ciliated adenocarcinoma of the cervix had prior liquid-based cervical cytology showing atypical, ciliated glandular cells that initially raised the diagnostic consideration of tubal metaplasia. A concurrent biopsy, however, revealed focally ciliated adenocarcinoma of the cervix. CONCLUSION: Awareness of the ciliated variant of adenocarcinoma of the cervix is important to avoid overreliance on ciliation as a definitive feature of benignity in cervical cytologic specimens.
Assuntos
Adenocarcinoma/patologia , Colo do Útero/patologia , Células Epiteliais/patologia , Ductos Paramesonéfricos/patologia , Neoplasias do Colo do Útero/patologia , Adulto , Colo do Útero/embriologia , Cílios/patologia , Diagnóstico Diferencial , Dietilestilbestrol/efeitos adversos , Feminino , Humanos , Ductos Paramesonéfricos/embriologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Esfregaço VaginalRESUMO
It has been questioned whether prenatal exposure to progesterone, like exposure to diethylstilbestrol (DES), results in teratogenic abnormalities of the upper and lower genital tract in human females. Through the use of a recently described model in which human fetal reproductive tracts can be transplanted and grown in vivo for extended periods in athymic nude mice, genital tracts from human female fetuses, ages 7 to 18 weeks postovulation, were grafted into castrated murine hosts and grown for 4 to 10 weeks in the presence or absence of continuous exposure to progesterone. Substantial growth was observed. For all specimens, the morphogenetic process proceeded normally, resulting in the harmonious organization of a complete, well differentiated genital tract composed of fallopian tubes, uterine corpus, and cervix and vagina. The fallopian tubes were highly convoluted and disclosed fimbria. The uterine corpus was lined by a simple columnar epithelium; two layers of stroma in the wall were distinctly separated from each other. In the older specimens, the outer layer of stroma had assumed microscopic properties diagnostic of smooth muscle (myometrium). In the majority of specimens the region of the cervix/vagina disclosed the development of a fornix-like evagination at which point or slightly cranially there was a gradual but defined transition from columnar epithelium to squamous epithelium. The inner layer of endometrial stroma tapered and disappeared at or close to the squamocolumnar junction. The vaginal stroma was a single homogeneous layer and was continuous with the myometrium of the uterine corpus. In the context of this model system, prenatal exposure of the developing human female genital tract of progesterone was not associated with any obvious teratogenic effects.
Assuntos
Genitália Feminina/embriologia , Progesterona/toxicidade , Animais , Colo do Útero/efeitos dos fármacos , Colo do Útero/embriologia , Tubas Uterinas/efeitos dos fármacos , Tubas Uterinas/embriologia , Feminino , Genitália Feminina/efeitos dos fármacos , Humanos , CamundongosRESUMO
The development of human fetal cervix has been systematically studied by SEM, obtaining a detailed map of its fine structure, particularly concerning the differentiation and maturation of the endocervical epithelium, including its "eversion" and "squamous metaplasia", normally occurring in postnatal life, but not yet observed in detail by electron microscopy in the fetus. Cervices from spontaneous abortion at 12, 15, 18, 20, 21 and 22 weeks and from intrauterine fetal death (hydrocephalus) at 31 weeks of development have been examined. At 12-15 weeks, as the canalization of the cervix proceeded, the endocervical epithelium consisted of high polyhedral cells, with regularly flattened or concave apices exhibiting scarce microvilli and often single primary cilia. Some narrow intercellular infoldings probably corresponded to primordial tubular glands. At the 18th week the epithelium was made up of a mosaic of flat or slightly raised polygonal cells, whose apical surface showed thin microplicae. At the 20th week a pseudostratified epithelium with many apically convex cells lined the cervical canal and the tubular glands. At 21 and 22 weeks "plicae palmatae" developed, covered by cells, often showing a smooth central area surrounded by microvilli, provided with a primary cilium and swollen by secretory material. This also formed rounded masses on the epithelium. In the lower part of the endocervix some very elongated cells showed short microplicae resulting from fusion of microvilli. At the 31st week secretion increased and its products spreading from the bottom of the glands contacted isolated ciliated cells at their openings and diffusely covered the surface epithelium. Most of the ectocervix exhibited squamous elements, with well-developed labyrinthine microplicae. These cells could overlap each other and also desquamate. The zone of the portio vaginalis around the os of the cervical canal appeared infolded and hypertrophic. Here, an indented squamo-columnar junction between the ectocervical and endocervical epithelium, caused by tongue-like prolongations of squamous epithelium directed toward the endocervix, was found. Their tips consisted of elongated cells, rich only in short microvilli. Our data indicate that the features of the microvillous cells are an expression of a hormone-dependent differentiative process. Thus, their secretion might be stimulated by progesterone. Similarly microplicae on the ectocervical epithelium (a sign of squamous maturation) might be promoted by estrogens. Furthermore, two aspects were significative: 1) the finding--in an early phase only (18th week)--of endocervically-located squamous cells, although devoid of microplicae; and 2) the occurrence--in the latest phase (31st week)--of an indented squamo-columnar junction on the surface of the portio. These features are in agreement with the caudal shift of the squamo-columnar junction near the uterine cavity to the ectocervix after cervico-vaginal demarcation; the squamous metaplasia of this everted endocervical epithelium has been reported by some authors. It is likely that these processes, occurring in fetal life as well as in pregnant women, are related to a common hormonal background, arising from the mother to her fetus.
Assuntos
Colo do Útero/ultraestrutura , Colo do Útero/embriologia , Epitélio/ultraestrutura , Feminino , Humanos , GravidezRESUMO
An unusual uterine malformation in which double cervix was the sole müllerian tube fusion defect is presented. It was associated with numerous other congenital anomalies in a 4-month-old infant with normal chromosome studies. The embryologic significance of this defective fusion is discussed.
Assuntos
Anormalidades Múltiplas/diagnóstico , Colo do Útero/anormalidades , Útero/anormalidades , Adolescente , Autopsia , Colo do Útero/embriologia , Feminino , Insuficiência Cardíaca/complicações , Humanos , Doença da Membrana Hialina/complicações , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez , Primeiro Trimestre da Gravidez , Útero/embriologiaRESUMO
Understanding of the development of the reproductive organs is essential to the evaluation of abnormalities in sexual differentiation. Recent advances resulting from application of genetic, biochemical, and ultrastructural techniques have helped to clarify the mechanisms regulating gonadal and reproductive tract development. The present review considers the major processes of sexual differentiation, development of the female reproductive system and development of the male reproductive system with emphasis on current understanding of basic regulatory mechanisms involved in normal and abnormal development of the reproductive organs.
Assuntos
Genitália Feminina/crescimento & desenvolvimento , Genitália Masculina/crescimento & desenvolvimento , Diferenciação Sexual , Colo do Útero/embriologia , Colo do Útero/crescimento & desenvolvimento , Tubas Uterinas/embriologia , Tubas Uterinas/crescimento & desenvolvimento , Feminino , Genitália Feminina/embriologia , Genitália Masculina/embriologia , Humanos , Masculino , Ovário/embriologia , Ovário/crescimento & desenvolvimento , Cromossomos Sexuais , Testículo/embriologia , Testículo/crescimento & desenvolvimento , Útero/embriologia , Útero/crescimento & desenvolvimento , Vagina/embriologia , Vagina/crescimento & desenvolvimentoRESUMO
The first case of a rare mullerian anomaly characterized by the presence of a complete uterine septum with duplication of the cervix and a longitudinal vaginal septum has been reported very recently. We present here three new cases of such an anomaly in an attempt to alert gynaecologists to the possible occurrence of such a malformation. The cases challenge the classical views of unidirectional (caudad to cranial) mullerian development and support the alternative embryologic hypothesis of Muller et al. according to which fusion and resorption begins at the isthmus and proceeds simultaneously in both the cranial and caudal directions.
Assuntos
Colo do Útero/anormalidades , Ductos Paramesonéfricos/anormalidades , Útero/anormalidades , Vagina/anormalidades , Adulto , Colo do Útero/embriologia , Feminino , Humanos , Útero/embriologia , Vagina/embriologiaRESUMO
The surface epithelium of the cervix undergoes change at many periods during life. The changes are principally due to the occurrence of metaplastic squamous epithelium within the transformation zone. This process seems to hold the key to an understanding of the origins of neoplastic development in the cervix. Cervical mucus secretion also seems to be dramatically influenced by this process.