RESUMO
OBJECTIVES: To assess embryonic genital tubercle using transvaginal three-dimensional (3D) ultrasound at 8-10+6 weeks of gestation. METHODS: One-hundred and two transvaginal 3D ultrasound scans were performed for first-trimester dating at 8-10+6 weeks of gestation. The genital tubercle angle (GTA) and genital tubercle length (GTL) were measured with a mid-sagittal view of the embryo using the 3D ultrasound multiplanar mode. Intra- and inter-observer agreements regarding GTA and GTL were also assessed with Bland-Altman plots and intra- and inter-correlation coefficients. RESULTS: There were no significant differences in GTA between male and female embryos at 8, 9, 10 weeks, or 8-10+6 weeks of gestation, respectively. There were also no significant differences in GTL between male and female embryos at 8, 9, 10 weeks, or 8-10+6 weeks of gestation, respectively. However, GTL increased linearly with advancing gestation (r=0.8276, p<0.00001). Mean GTL (SD) values at 8, 9, and 10 weeks were 0.833â¯mm (0.274), 1.623â¯mm (0.262), and 2.152â¯mm (0.420), respectively (p<0.001). Intra- and inter-reproducibilities of GTA and GTL were excellent. The intra- and inter-correlation coefficients of GTA and GTL were 0.964 and 0.995, and 0.996 and 0.9933, respectively. CONCLUSIONS: The genital tubercle could be identified using transvaginal 3D ultrasound at 8-10+6 weeks of gestation. However, sex differentiation could not be performed at this age. The genital tubercle linearly developed with advancing gestation during the mid-first trimester of pregnancy.
Assuntos
Imageamento Tridimensional , Primeiro Trimestre da Gravidez , Ultrassonografia Pré-Natal , Humanos , Feminino , Gravidez , Ultrassonografia Pré-Natal/métodos , Imageamento Tridimensional/métodos , Masculino , Adulto , Idade Gestacional , Genitália Feminina/diagnóstico por imagem , Genitália Feminina/embriologiaRESUMO
The reproductive tract in mammals emerges from two ductal systems during embryogenesis: Wolffian ducts (WDs) and Mullerian ducts (MDs). Most of the female reproductive tract (FRT) including the oviducts, uterine horn and cervix, originate from MDs. It is widely accepted that the formation of MDs depends on the preformed WDs within the urogenital primordia. Here, we found that the WD mesenchyme under the regulation of Hedgehog (Hh) signaling is closely related to the developmental processes of the FRT during embryonic and postnatal periods. Deficiency of Sonic hedgehog (Shh), the only Hh ligand expressed exclusively in WDs, prevents the MD mesenchyme from affecting uterine growth along the radial axis. The in vivo cell tracking approach revealed that after WD regression, distinct cells responding to WD-derived Hh signal continue to exist in the developing FRT and gradually contribute to the formation of various tissues such as smooth muscle, endometrial stroma and vascular vessel, in the mouse uterus. Our study thus provides a novel developmental mechanism of FRT relying on WD.
Assuntos
Genitália Feminina/embriologia , Genitália Feminina/metabolismo , Proteínas Hedgehog/metabolismo , Organogênese , Transdução de Sinais , Útero/embriologia , Útero/metabolismo , Animais , Biomarcadores , Diferenciação Celular , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Imuno-Histoquímica , Camundongos , Camundongos Knockout , Modelos Biológicos , Ductos Paramesonéfricos/embriologia , Ductos Paramesonéfricos/metabolismo , Organogênese/genéticaRESUMO
Structural anomalies of the female reproductive tract, known as Mullerian anomalies, can occur in isolation or in association with anomalies of other organ systems. Due to shared embryology, the most common association in up to 40% of patients is with renal, ureteral, and bladder anomalies. Affected girls can have a wide range of genitourinary symptoms with urologists playing an integral role in their diagnosis and treatment. To facilitate the recognition and management of these conditions, we provide a review of Mullerian anomalies including the embryology, classifications, syndromes, evaluation, and treatments with attention to their urologic applicability.
Assuntos
Ductos Paramesonéfricos/anormalidades , Anormalidades Urogenitais/complicações , Transtornos 46, XX do Desenvolvimento Sexual/complicações , Malformações Anorretais/complicações , Anus Imperfurado/complicações , Anormalidades Congênitas , Feminino , Genitália Feminina/embriologia , Hérnia Umbilical/complicações , Humanos , Escoliose/complicações , Sistema Urinário/embriologia , Anormalidades Urogenitais/classificação , Anormalidades Urogenitais/diagnóstico , Anormalidades Urogenitais/terapiaRESUMO
Exposures to adverse conditions in utero can lead to permanent changes in the structure and function of key physiological systems in the developing fetus, increasing the risk of disease and premature aging in later postnatal life. When considering the systems that could be affected by an adverse gestational environment, the reproductive system of developing female offspring may be particularly important, as changes have the potential to alter both reproductive capacity of the first generation, as well as health of the second generation through changes in the oocyte. The aim of this review is to examine the impact of different adverse intrauterine conditions on the reproductive system of the female offspring. It focuses on the effects of exposure to maternal undernutrition, overnutrition/obesity, hypoxia, smoking, steroid excess, endocrine-disrupting chemicals, and pollutants during gestation and draws on data from human and animal studies to illuminate underlying mechanisms. The available data indeed indicate that adverse gestational environments alter the reproductive physiology of female offspring with consequences for future reproductive capacity. These alterations are mediated via programmed changes in the hypothalamic-pituitary-gonadal axis and the structure and function of reproductive tissues, particularly the ovaries. Reproductive programming may be observed as a change in the timing of puberty onset and menopause/reproductive decline, altered menstrual/estrous cycles, polycystic ovaries, and elevated risk of reproductive tissue cancers. These reproductive outcomes can affect the fertility and fecundity of the female offspring; however, further work is needed to better define the possible impact of these programmed changes on subsequent generations.
Assuntos
Desenvolvimento Embrionário/fisiologia , Genitália Feminina/embriologia , Animais , Feminino , Fertilidade/fisiologia , Genitália Feminina/metabolismo , Humanos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Reprodução/fisiologia , Maturidade Sexual/fisiologiaRESUMO
The spotted hyaena (Crocuta crocuta) is a unique species, even amongst the Hyaenidae. Extreme clitoral development in female spotted hyaenas challenges aspects of the accepted framework of sexual differentiation and reproductive function. They lack a vulva and instead urinate, copulate and give birth through a single, long urogenital canal that traverses a clitoris superficially resembling a penis. Recent and historical evidence is reviewed to describe our changing understanding of the biology of this species. Expanding upon observations from hyaenas in nature, much has been learned from studies utilising the captive colony at the University of California, Berkeley. The steroid environment of pregnancy is shaped by placental androgen and oestrogen secretion and a late gestational increase in sex hormone binding globulin, the regulated expression and steroid-binding characteristics of which are unique within the Hyaenidae. While initial external genital development is largely free of androgenic influence, the increase in testosterone concentrations in late gestation influences foetal development. Specifically, anti-androgen (AA) treatment of pregnant females reduced the developmental influence of androgens on their foetuses, resulting in reduced androstenedione concentrations in young females and easier birth through a 'feminised' clitoris, but precluded intromission and mating by 'feminised' male offspring, and altered social interactions. Insight into the costs and benefits of androgen exposure on spotted hyaena reproductive development, endocrinology and behaviour emphasises the delicate balance that sustains reproductive success, forces a re-evaluation of how we define masculine vs feminine sexual characteristics, and motivates reflection about the representative value of model species.
Assuntos
Genitália Feminina , Genitália Masculina , Hormônios Esteroides Gonadais/fisiologia , Hyaenidae , Reprodução/fisiologia , Diferenciação Sexual/fisiologia , Androgênios/fisiologia , Animais , Estrogênios/fisiologia , Feminino , Genitália Feminina/anatomia & histologia , Genitália Feminina/embriologia , Genitália Feminina/crescimento & desenvolvimento , Genitália Masculina/anatomia & histologia , Genitália Masculina/embriologia , Genitália Masculina/crescimento & desenvolvimento , Hyaenidae/anatomia & histologia , Hyaenidae/embriologia , Hyaenidae/fisiologia , Masculino , Gravidez , Globulina de Ligação a Hormônio Sexual/fisiologia , Comportamento Sexual Animal/fisiologiaRESUMO
Numerous evidences have alerted on the toxic effects of the exposure to glyphosate on living organisms. Glyphosate is the herbicide most used in crops such as maize and soybean worldwide, which implies that several non-target species are at a high risk of exposure. Although the Environmental Protection Agency (EPA-USA) has reaffirmed that glyphosate is safe for users, there are controversial studies that question this statement. Some of the reported effects are due to exposure to high doses; however, recent evidences have shown that exposure to low doses could also alter the development of the female reproductive tract, with consequences on fertility. Different animal models of exposure to glyphosate or glyphosate-based herbicides (GBHs) have shown that the effects on the female reproductive tract may be related to the potential and/or mechanisms of actions of an endocrine-disrupting compound. Studies have also demonstrated that the exposure to GBHs alters the development and differentiation of ovarian follicles and uterus, affecting fertility when animals are exposed before puberty. In addition, exposure to GBHs during gestation could alter the development of the offspring (F1 and F2). The main mechanism described associated with the endocrine-disrupting effect of GBHs is the modulation of estrogen receptors and molecules involved in the estrogenic pathways. This review summarizes the endocrine-disrupting effects of exposure to glyphosate and GBHs at low or "environmentally relevant" doses in the female reproductive tissues. Data suggesting that, at low doses, GBHs may have adverse effects on the female reproductive tract fertility are discussed.
Assuntos
Disruptores Endócrinos/toxicidade , Fertilidade/efeitos dos fármacos , Glicina/análogos & derivados , Herbicidas/toxicidade , Animais , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/fisiologia , Feminino , Genitália Feminina/efeitos dos fármacos , Genitália Feminina/embriologia , Genitália Feminina/crescimento & desenvolvimento , Glicina/química , Glicina/toxicidade , Herbicidas/química , Humanos , Infertilidade Feminina/induzido quimicamente , Infertilidade Feminina/epidemiologia , Reprodução/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , GlifosatoRESUMO
Genital tubercle has bisexual potential before sex differentiation. Females exposed to androgen during sex differentiation show masculinized external genitalia, but the effects of different androgens on tubular urethral and penile formation in females are mostly unknown. In this study, we compared the masculinization effects of commonly used androgens methyltestosterone, dihydrotestosterone, and testosterone on the induction of penile formation in females. Our results suggested that prenatal treatment with low doses of methyltestosterone, but not same doses of dihydrotestosterone or testosterone, could induce penile formation in female mice. The minimum dose of dihydrotestosterone and testosterone for inducing tubular urethral formation in female mice was, respectively, 50 and 20 times higher than that of methyltestosterone. In vivo methyltestosterone treatment induced more nuclear translocation of androgen receptors in genital tubercles of female mice, affected Wnt signaling gene expressions, and then led to similar patterns of cell proliferation and death in developing genital tubercles to those of control males. We further revealed that low-dose methyltestosterone, but not same dose of dihydrotestosterone or testosterone, treatment induced penile formation in female guinea pigs. Exposure of female mouse genital tubercle organ culture to methyltestosterone, dihydrotestosterone, or testosterone could induce nuclear translocation of androgen receptors, suggesting that the differential effect of the three androgens in vivo might be due to the hormonal profile in mother or fetus, rather than the local genital tissue. To understand the differential role of these androgens in masculinization process involved is fundamental to androgen replacement therapy for diseases related to external genital masculinization.
Assuntos
Di-Hidrotestosterona/efeitos adversos , Genitália Feminina/embriologia , Metiltestosterona/efeitos adversos , Pênis/crescimento & desenvolvimento , Testosterona/farmacologia , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Antagonistas de Androgênios/administração & dosagem , Antagonistas de Androgênios/farmacologia , Animais , Animais Recém-Nascidos , Morte Celular , Proliferação de Células , Quimioterapia Combinada , Feminino , Flutamida/administração & dosagem , Flutamida/farmacologia , Genitália Feminina/crescimento & desenvolvimento , Cobaias , Masculino , Camundongos , Gravidez , Receptores Androgênicos , Análise para Determinação do Sexo , Testosterona/administração & dosagemRESUMO
Infections of the male and female reproductive system can lead to significant morbidity and mortality. This article will review the relevant embryology and anatomy of the male and female reproductive systems and will discuss the imaging findings of different infections. An understanding of the clinical presentation and imaging findings of infections of the reproductive system is critical in order to allow for prompt and accurate diagnosis. A delay in diagnosis for these infections can have significant morbidity, and occasional mortality.
Assuntos
Doenças dos Genitais Femininos/diagnóstico por imagem , Doenças dos Genitais Femininos/microbiologia , Doenças dos Genitais Masculinos/diagnóstico por imagem , Doenças dos Genitais Masculinos/microbiologia , Genitália Feminina/anatomia & histologia , Genitália Masculina/anatomia & histologia , Infecções/diagnóstico por imagem , Infecções/microbiologia , Diagnóstico Diferencial , Feminino , Genitália Feminina/embriologia , Genitália Masculina/embriologia , Humanos , MasculinoRESUMO
The prostate is an accessory reproductive gland that is sensitive to the action of exogenous compounds known as endocrine disrupters that alter normal hormonal function. Finasteride is a widely used chemical that acts to inhibit the conversion of testosterone in its most active form, dihydrotestosterone. It is known that intrauterine exposure to finasteride causes changes in the male prostate even at low dosages; however, it is not known whether these dosages are capable of causing changes in the female prostate, which is present in a large number of mammalian species, including humans. In the present study, histochemistry, immunohistochemistry, immunofluorescence, serological dosages, and three-dimensional reconstruction techniques were employed to evaluate the effects of intrauterine exposure to a low dose of finasteride (100 µg.BW/d) on postnatal prostate development in male and female Mongolian gerbils. The results indicate that the gerbil female prostate also undergoes alterations following intrauterine exposure to finasteride, exhibiting a thickening of periductal smooth muscle and increased stromal proliferation. There are also intersex differences in the impact of exposure on the expression of the androgen receptor, which was increased in males, and of the estrogen-α receptor, which was decreased in the male prostate but unchanged in females. Altogether, this study indicates there are sex differences in the effects of finasteride exposure even at low dosages.
Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Finasterida/toxicidade , Genitália Feminina/efeitos dos fármacos , Gerbillinae/embriologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Próstata/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Feminino , Genitália Feminina/embriologia , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Próstata/embriologia , Receptores Androgênicos/metabolismo , Reprodução/efeitos dos fármacos , Testosterona/metabolismoRESUMO
In horses, pregnancy is characterized by high levels of maternal estrogens that are produced largely by the interstitial tissue inside the gonads of the offspring, associated with a physiological gonadal hyperplasia, that is uncommon in other species. However, a detailed structural-functional understanding of the early stages of gonadal development and hyperplasia has remained elusive in horse pregnancy because of the lack of substantial data. The goal of this study was to describe the genital organs' development in 19 early horse embryos and fetuses (days 20-140 of gestation) of both sexes by means of anatomy, histology, stereology, and immunohistochemistry, with a specific focus on gonadal hyperplasia and interstitial tissue development. Gonadal hyperplasia with similar amounts of interstitial cells was observed in both sexes, but only during the early stage of development (days 40-90). Surprisingly, a higher degree of hyperplasia, characterized by larger amounts of interstitial cell-rich areas, was seen in fetal ovaries from 90 days of gestation onwards. Another novel aspect was that parallel to the hyperplasia of the interstitial cells, a much more precocious and pronounced differentiation of germinal cells was seen in the ovary, characterized by an earlier peak and decrease of DAZL and OCT protein immune markers. In conclusion, a reduced degree of hyperplasia and interstitial tissue in the fetal testis after 90 days of gestation suggests the existence of a more efficient mechanism regarding the synthesis of estrogen precursors as a structural or physiological difference between both fetal sexes, which warrants further investigation.
Assuntos
Genitália Feminina/embriologia , Genitália Masculina/embriologia , Cavalos/embriologia , Animais , Feminino , Desenvolvimento Fetal/fisiologia , Masculino , GravidezRESUMO
Cysteinerich angiogenic inducer 61 (CCN1/Cyr61) is a prompt response transcription product activated by growth factors. As a member of the CCN family, it mediates cell survival, proliferation, differentiation, migration, adhesion and synthesis of the extracellular matrix by binding directly to the integrins and heparin sulfate proteoglycans or activating multiple signaling transduction pathways. It has previously been demonstrated that CCN1/Cyr61 exhibits an important role in the female reproductive system during embryogenesis and tumorigenesis. However, the functions of CCN1/Cyr61 in the female reproductive system have not been systematically investigated, therefore, the primary aim of the present review is to introduce the role and function of CCN1/Cyr61 in the female reproductive system. The current review presents the molecular structure and biological function of CCN1/Cyr61 and provides detailed data on its expression pattern and contribution to the female reproductive system, including the role in embryogenesis and tumorigenesis.
Assuntos
Transformação Celular Neoplásica/genética , Proteína Rica em Cisteína 61/genética , Desenvolvimento Embrionário/genética , Genitália Feminina/embriologia , Genitália Feminina/metabolismo , Animais , Transformação Celular Neoplásica/metabolismo , Proteína Rica em Cisteína 61/química , Proteína Rica em Cisteína 61/metabolismo , Suscetibilidade a Doenças , Feminino , Regulação da Expressão Gênica , Humanos , Neovascularização Fisiológica/genética , Osteogênese , Transdução de SinaisRESUMO
Childbirth can be a traumatic experience on the female body. Some techniques may be implemented to make the process smoother and decrease the potential lacerations that can occur. Episiotomies have been used by obstetricians and midwives to help make the fetal decent down the vaginal canal less turbulent. A physician must use his best judgment on when it is necessary to make this incision and what form of incision to make. Before making an incision one must understand the female external and internal anatomy and thoroughly comprehend the stages of birth to understand how and what complications can occur. Even though an episiotomy is a minor incision, it is still a surgical incision nonetheless and as with any form of surgery there are both risks and benefits that are to be considered. Nevertheless, episiotomies have proven to help ease births that are complicated by shoulder dystocia, prevent severe lacerations, and decrease the second stage of labor. The following comprehensive review provides a description of the female anatomy, as well as an extensive description of why, when, and how an episiotomy is done. Clin. Anat. 30:362-372, 2017. © 2017 Wiley Periodicals, Inc.
Assuntos
Parto Obstétrico/efeitos adversos , Episiotomia/métodos , Genitália Feminina/embriologia , Períneo/cirurgia , Episiotomia/efeitos adversos , Episiotomia/história , Feminino , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Segunda Fase do Trabalho de Parto/fisiologia , Lacerações/prevenção & controle , Períneo/anatomia & histologia , Gravidez , Fatores de RiscoRESUMO
Reciprocal epithelial-mesenchymal interactions and several signalling pathways regulate the development of the genital tubercle (GT), an embryonic primordium of external genitalia. The morphology of the adult male external genitalia of the Asian house musk shrew Suncus murinus (hereafter, laboratory name: suncus) belonging to the order Eulipotyphla (the former order Insectivora or Soricomorpha) differs from those of mice and humans. However, the developmental process of the suncus GT and its regulatory genes are unknown. In the present study, we explored the morphological changes and gene expression patterns during the development of the suncus GT. Morphological observations suggested the presence of common (during the initial outgrowth) and species-specific (during the sexual differentiation of GT) developmental processes of the suncus GT. In gene expression analysis, fibroblast growth factor 8 (Fgf8) and sonic hedgehog (Shh), an indicator and regulator of GT development in mice respectively, were found to be expressed in the cloacal epithelium and the developing urethral epithelium of the suncus GT. This pattern of expression specifically in GT epithelium is similar to that observed in the developing mouse GT. Our results indicate that the mechanism of GT formation regulated by the FGF and SHH signalling pathways is widely conserved in mammals.
Assuntos
Fator 8 de Crescimento de Fibroblasto/genética , Expressão Gênica , Genitália/crescimento & desenvolvimento , Genitália/metabolismo , Proteínas Hedgehog/genética , Musaranhos/crescimento & desenvolvimento , Animais , Cloaca/embriologia , Cloaca/metabolismo , Epitélio/embriologia , Epitélio/metabolismo , Feminino , Fator 8 de Crescimento de Fibroblasto/fisiologia , Perfilação da Expressão Gênica , Genitália/embriologia , Genitália Feminina/embriologia , Genitália Feminina/crescimento & desenvolvimento , Genitália Feminina/metabolismo , Genitália Masculina/embriologia , Genitália Masculina/crescimento & desenvolvimento , Genitália Masculina/metabolismo , Proteínas Hedgehog/fisiologia , Humanos , Masculino , Camundongos , Microscopia Eletrônica de Varredura , Caracteres Sexuais , Transdução de Sinais/fisiologia , Uretra/embriologia , Uretra/metabolismoRESUMO
INTRODUCTION: Early ultrasound fetal sex determination is of obvious interest, particularly in the context of X-linked diseases. In the human, the anogenital distance, i.e., the distance between the caudal end and the base of the genital tubercule is sexually dimorphic. This difference is apparent from 11 weeks of gestation. The aim of this prospective study was to evaluate the accuracy of anogenital distance measurement during the first trimester ultrasound in the early determination of fetal gender. MATERIALS AND METHODS: Fetal gender was assessed by ultrasound in 310 singleton pregnancies at 11-14 weeks of gestation. The optimal cut-off was determined by the minimal p-value technic and validated using bootstrap simulation. RESULTS: 310 women were included. A cut-off of 4.8mm was determined to predict male (≥4.8mm) or female (<4.8mm) fetuses. Sex was correctly determined for 87% of the males and 89% of the females. The inter-observer variability was excellent. CONCLUSION: This study presents a new sonographic sign for early fetal sex determination that has not been previously explored. It appears to be an accurate tool but it requires further validation in larger series.
Assuntos
Canal Anal/diagnóstico por imagem , Genitália Feminina/diagnóstico por imagem , Genitália Masculina/diagnóstico por imagem , Análise para Determinação do Sexo , Ultrassonografia Pré-Natal , Canal Anal/embriologia , Simulação por Computador , Estatura Cabeça-Cóccix , Feminino , França , Genitália Feminina/embriologia , Genitália Masculina/embriologia , Idade Gestacional , Humanos , Perda de Seguimento , Masculino , Variações Dependentes do Observador , Gravidez , Primeiro Trimestre da Gravidez , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos Testes , Caracteres SexuaisRESUMO
The molecular signaling processes involved the differentiation of the Müllerian duct (MD) into the female reproductive tract, or oviduct, in non-mammalian vertebrates are not well understood. Studies in mammals and birds indicate that steroid hormones play a role in this process, as the embryonic MD has been shown to be vulnerable to exogenous estrogens and progestins and environmental endocrine disrupting contaminants. In a previous study, developmental treatment with an estrogen receptor α (ERα) agonist, 4,4',4â³-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT), induced significant enlargement of the MD in alligator embryos incubated at a male-producing temperature, which was not observed in embryos treated with an estrogen receptor ß (ERß) agonist, 7-bromo-2-(4-hydroxyphenyl)-1,3-benzoxazol-5-ol (WAY 200070), or with 17ß-estradiol (E2). In order to understand the role of estrogen signaling in female alligator oviduct development, we incubated eggs at a female-producing temperature and treated them with E2 and these ER selective agonists, PPT and WAY 200070, just prior to the thermosensitive window of sex determination. At stage 27, one stage prior to hatching, PPT induced significant enlargement of the MD with precocious development of secretory glands and connective tissue differentiation similar to characteristics of mature adult oviduct. PPT treatment in ovo increased mRNA expression of ERß, progesterone receptor, androgen receptor and insulin-like growth factor 1 in MD at stage 27, while expression of ERα was decreased. Neither WAY 200070 nor E2 treatment induced these effects seen in PPT-treated MD. The results of this study provide insight into the critical factors for healthy reproductive system formation in this sentinel species, although further investigation is needed to determine whether the observed phenomena are directly due to selective stimulation of ERα or related to some other aspect of PPT treatment.
Assuntos
Jacarés e Crocodilos/embriologia , Jacarés e Crocodilos/metabolismo , Receptor alfa de Estrogênio/agonistas , Genitália Feminina/embriologia , Animais , Embrião não Mamífero/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Receptor alfa de Estrogênio/metabolismo , Feminino , Genitália Feminina/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Ductos Paramesonéfricos/efeitos dos fármacos , Ductos Paramesonéfricos/embriologia , Ductos Paramesonéfricos/metabolismo , Oxazóis/farmacologia , Fenóis/farmacologia , Pirazóis/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Estados UnidosRESUMO
Studies report that fetal exposure to paracetamol/acetaminophen by maternal consumption can interfere with male reproductive development. Moreover, recent biomonitoring data report widespread presence of paracetamol in German and Danish populations, suggesting exposure via secondary (nonpharmaceutical) sources, such as metabolic conversion from the ubiquitous industrial compound aniline. In this study, we investigated the extent to which paracetamol and aniline can interfere with female reproductive development. Intrauterine exposure to paracetamol by gavage of pregnant dams resulted in shortening of the anogenital distance in adult offspring, suggesting that fetal hormone signaling had been disturbed. Female offspring of paracetamol-exposed mothers had ovaries with diminished follicle reserve and reduced fertility. Fetal gonads of exposed animals had also reduced gonocyte numbers, suggesting that the reduced follicle count in adults could be due to early disruption of germ cell development. However, ex vivo cultures of ovaries from 12.5 days post coitum fetuses showed no decrease in proliferation or expression following exposure to paracetamol. This suggests that the effect of paracetamol occurs prior to this developmental stage. Accordingly, using embryonic stem cells as a proxy for primordial germ cells we show that paracetamol is an inhibitor of cellular proliferation, but without cytotoxic effects. Collectively, our data show that intrauterine exposure to paracetamol at levels commonly observed in pregnant women, as well as its precursor aniline, may block primordial germ cell proliferation, ultimately leading to reduced follicle reserves and compromised reproductive capacity later in life.
Assuntos
Acetaminofen/toxicidade , Compostos de Anilina/toxicidade , Fertilidade/efeitos dos fármacos , Genitália Feminina/anormalidades , Folículo Ovariano/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Animais , Feminino , Genitália Feminina/embriologia , Idade Gestacional , Masculino , Camundongos Endogâmicos C57BL , Folículo Ovariano/embriologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologiaRESUMO
BACKGROUND: Common uterine anomalies are important owing to their impact on fertility, and complex mesonephric anomalies and certain Müllerian malformations are particularly important because they cause serious clinical symptoms and affect woman's quality of life, in addition to creating fertility problems. In these cases of complex female genital tract malformations, a correct diagnosis is essential to avoid inappropriate and/or unnecessary surgery. Therefore, acquiring and applying the appropriate embryological knowledge, management and therapy is a challenge for gynaecologists. Here, we considered complex malformations to be obstructive anomalies and/or those associated with cloacal and urogenital sinus anomalies, urinary and/or extragenital anomalies, or other clinical implications or symptoms creating a difficult differential diagnosis. METHODS: A diligent and comprehensive search of PubMed and Scopus was performed for all studies published from 1 January 2011 to 15 April 2015 (then updated up to September 2015) using the following search terms: 'management' in combination with either 'female genital malformations' or 'female genital tract anomalies' or 'Müllerian anomalies'. The MeSH terms 'renal agenesis', 'hydrocolpos', 'obstructed hemivagina' 'cervicovaginal agenesis or atresia', 'vaginal agenesis or atresia', 'Herlyn-Werner-Wunderlich syndrome', 'uterine duplication' and 'cloacal anomalies' were also used to compile a list of all publications containing these terms since 2011. The basic embryological considerations for understanding female genitourinary malformations were also revealed. Based on our experience and the updated literature review, we studied the definition and classification of the complex malformations, and we analysed the clinical presentation and different therapeutic strategies for each anomaly, including the embryological and clinical classification of female genitourinary malformations. RESULTS: From 755 search retrieved references, 230 articles were analysed and 120 studied in detail. They were added to those included in a previous systematic review. Here, we report the clinical presentation and management of: agenesis or hypoplasia of one urogenital ridge; unilateral renal agenesis and ipsilateral blind or obstructed hemivagina or unilateral cervicovaginal agenesis; cavitated and non-communicating uterine horns and Müllerian atresias or agenesis, including Rokitansky syndrome; anomalies of the cloaca and urogenital sinus, including congenital vagino-vesical fistulas and cloacal anomalies; malformative combinations and other complex malformations. The clinical symptoms and therapeutic strategies for each complex genitourinary malformation are discussed. In general, surgical techniques to correct genital malformations depend on the type of anomaly, its complexity, the patient's symptoms and the correct embryological interpretation of the anomaly. Most anomalies can typically be resolved vaginally or by hysteroscopy, but laparoscopy or laparotomy is often required as well. We also include additional discussion of the catalogue and classification systems for female genital malformations, the systematic association between renal agenesis and ipsilateral genital malformation, and accessory and cavitated uterine masses. CONCLUSIONS: Knowledge of the correct genitourinary embryology is essential for the understanding, study, diagnosis and subsequent treatment of genital malformations, especially complex ones and those that lead to gynaecological and reproductive problems, particularly in young patients. Some anomalies may require complex surgery involving multiple specialties, and patients should therefore be referred to centres that have experience in treating complex genital malformations.
Assuntos
Genitália Feminina/anormalidades , Anormalidades Congênitas/diagnóstico , Anormalidades Congênitas/terapia , Diagnóstico Precoce , Feminino , Genitália Feminina/embriologia , Humanos , Rim/anormalidades , Nefropatias/congênito , Nefropatias/diagnóstico , Nefropatias/terapia , Qualidade de Vida , Reprodução , Procedimentos Desnecessários , Anormalidades Urogenitais/diagnóstico , Anormalidades Urogenitais/terapia , Útero/anormalidades , Vagina/anormalidadesRESUMO
Correct sexual development is arguably the most important trait in an organism's life history since it is directly related to its genetic fitness. The developing gonad houses the germ cells, the only legacy we pass on to subsequent generations. Given the pivotal importance of correct reproductive function, it is confounding that disorders of sex development (DSDs) are among the most common congenital abnormalities in humans (Lee et al. J Pediatr Urol 8(6):611-615, 2012). Urogenital development is a highly complex process involving coordinated interactions between molecular and hormonal pathways in a tightly regulated order. The controls that regulate some of the key events in this process are beginning to be unraveled. This chapter provides an overview of our understanding of urogenital development from the gonads to the urogenital ducts and external genitalia.
Assuntos
Genitália Feminina/anatomia & histologia , Genitália Feminina/embriologia , Genitália Masculina/anatomia & histologia , Genitália Masculina/embriologia , Animais , Feminino , Humanos , MasculinoRESUMO
HOX genes convey positional identity that leads to the proper partitioning and adult identity of the female reproductive track. Abnormalities in reproductive tract development can be caused by HOX gene mutations or altered HOX gene expression. Diethylstilbestrol (DES) and other endocrine disruptors cause Müllerian defects by changing HOX gene expression. HOX genes are also essential regulators of adult endometrial development. Regulated HOXA10 and HOXA11 expression is necessary for endometrial receptivity; decreased HOXA10 or HOXA11 expression leads to decreased implantation rates. Alternation of HOXA10 and HOXA11 expression has been identified as a mechanism of the decreased implantation associated with endometriosis, polycystic ovarian syndrome, leiomyoma, polyps, adenomyosis, and hydrosalpinx. Alteration of HOX gene expression causes both uterine developmental abnormalities and impaired adult endometrial development that prevent implantation and lead to female infertility.
Assuntos
Transtornos do Desenvolvimento Sexual/genética , Fertilidade/genética , Genes Homeobox/genética , Genitália Feminina/embriologia , Infertilidade Feminina/genética , Adulto , Implantação do Embrião/genética , Estrogênios/metabolismo , Feminino , Regulação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Genes Homeobox/fisiologia , Proteínas Homeobox A10 , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/fisiologia , Humanos , Ductos Paramesonéfricos/embriologia , Ductos Paramesonéfricos/metabolismo , Progesterona/metabolismoRESUMO
Epithelial ovarian cancer comprises â¼85% of all ovarian cancer cases. Despite acceptance regarding the influence of reproductive hormones on ovarian cancer risk and considerable advances in the understanding of epithelial ovarian carcinogenesis on a molecular level, complete understanding of the biologic processes underlying malignant transformation of ovarian surface epithelium is lacking. Various hypotheses have been proposed over the past several decades to explain the etiology of the disease. The role of reproductive hormones in epithelial ovarian carcinogenesis remains a key topic of research. Primary questions in the field of ovarian cancer biology center on its developmental cell of origin, the positive and negative effects of each class of hormones on ovarian cancer initiation and progression, and the role of the immune system in the ovarian cancer microenvironment. The development of the female reproductive tract is dictated by the hormonal milieu during embryogenesis. Intensive research efforts have revealed that ovarian cancer is a heterogenous disease that may develop from multiple extra-ovarian tissues, including both Müllerian (fallopian tubes, endometrium) and non-Müllerian structures (gastrointestinal tissue), contributing to its heterogeneity and distinct histologic subtypes. The mechanism underlying ovarian localization, however, remains unclear. Here, we discuss the role of reproductive hormones in influencing the immune system and tipping the balance against or in favor of developing ovarian cancer. We comment on animal models that are critical for experimentally validating existing hypotheses in key areas of endocrine research and useful for preclinical drug development. Finally, we address emerging therapeutic trends directed against ovarian cancer.