Advances in Anatomy Embryology and Cell Biology最新文献

The preimplantation mammalian embryo is a simplistic, self-contained, and a superior model for investigating the inherent complexities of cell fate decision mechanisms. All mammals begin their humble journey from a single-cell fertilized zygote contained within a proteinaceous coat called the zona pellucida. The zygote embarks on a series of well-orchestrated events, beginning with the activation of embryonic genome, transition from meiotic to mitotic divisions, spatial organization of the cells, timely differentiation into committed trophectoderm (TE) and primitive endoderm (PrE), and ultimately escape from zona pellucida for implantation into the uterus. The entire development of preimplantation embryo can be studied in vitro using a minimalistic and defined culture system. The ease of culture along with the ability to manipulate gene expression and image the embryos makes them an ideal model system for investigation into the first two of several cell fate decisions made by the embryo that result in a pluripotent epiblast (EPI) and differentiated TE and PrE lineages. This chapter reviews our latest knowledge of preimplantation embryo development, setting the stage for understanding placental development in subsequent chapters in this Book.

In comparison to many other mammalian species, ruminant ungulates have a unique form of placentation. Ruminants initially display an epitheliochorial type of placentation; however, during the period of placental attachment, trophoblast giant binucleate cells (BNC) develop within the chorion to migrate and fuse with the uterine surface epithelium to form syncytial plaques. Binucleate cell migration and fusion continues throughout pregnancy but never appears to breach the basal lamina, beneath the uterine surface or luminal epithelium. Therefore, the semi-invasive type of placentation in ruminants is classified as synepitheliochorial. The endometrium of ruminant species also contains unique specialized aglandular structures termed "caruncles" in which the chorioallantois (cotyledons) interdigitates and forms highly vascularized fetal-maternal "placentomes." This chapter will discuss the current knowledge of early conceptus development during the peri-attachment period, establishment of pregnancy, conceptus attachment, and placentation in ruminant ungulates. The features of placentomes, BNCs, fetomaternal hybrid cells, and multinucleated syncytial plaques of the cotyledonary placenta of ruminant species will be reviewed to highlight the unique form of placentation compared to the placentae of other artiodactyls.

Placenta forms as a momentary organ inside the uterus with a slew of activities only when the woman is pregnant. It is a discoid-shaped hybrid structure consisting of maternal and embryonic components. It develops in the mesometrial side of the uterus following blastocyst implantation to keep the two genetically different entities, the mother and embryo, separated but connected. The beginning and progression of placental formation and development following blastocyst implantation coincides with the chronological developmental stages of the embryo. It gradually acquires the ability to perform the vascular, respiratory, hepatic, renal, endocrine, gastrointestinal, immune, and physical barrier functions synchronously that are vital for fetal development, growth, and safety inside the maternal environment. The uterus ejects the placenta when its embryonic growth and survival supportive roles are finished; that is usually the birth of the baby. Despite its irreplaceable role in fetal development and survival over the post-implantation progression of pregnancy, it still remains unclear how it forms, matures, performs all of its activities, and starts to fail functioning. Thus, a detailed understanding about normal developmental, structural, and functional aspects of the placenta may lead to avoid pregnancy problems that arise with the placenta.

Endometriosis, the presence and growth of uterine endometrial glandular epithelial and stroma cells outside the uterine cavity, causes pain and infertility in women and girls of reproductive age. As randomized, double-blinded, controlled studies of endometriosis in women are impractical and at times ethically prohibitive, animal models for endometriosis arose as an important adjunct to gain mechanistic insights into the etiology and pathophysiological mechanisms of this perplexing disorder. A more thorough understanding of endometriosis in women may help develop novel noninvasive diagnostics, classification systems, therapeutic regimes, and even preventative methods for the management of endometriosis. This chapter is intended to introduce a brief historical background, biological and epidemiological aspects, the major symptoms, the effects of endocrine-disrupting chemicals, and an example of an epigenetic factor of endometriosis in women.

Pelvic pain is a common symptom of endometriosis. Our understanding of its etiology remains incomplete and medical management is limited by poor translation from preclinical models to clinical trials. In this review, we briefly consider the evidence, or lack thereof, that different subtypes of lesion, extra-uterine bleeding, and neuropathic pathways add to the complex and heterogeneous pain experience of women with the condition. We summarize the studies in rodent models of endometriosis that have used behavioral endpoints (evoked and non-evoked) to explore mechanisms of endometriosis-associated pain. Lesion innervation, activation of nerves by pronociceptive molecules released by immune cells, and a role for estrogen in modulating hyperalgesia are key endometriosis-associated pain mechanisms replicated in preclinical rodent models. The presence of ectopic (full thickness uterus or endometrial) tissue may be associated with changes in the spinal cord and brain, which appear to model changes reported in patients. While preclinical models using rats and mice have yielded insights that appear relevant to mechanisms responsible for the development of endometriosis-associated pain, they are limited in scope. Specifically, most studies are based on models that only resulted in the formation of superficial lesions and use induced (evoked) behavioral 'pain' tests. We suggest that translation for patient benefit will be improved by new approaches including models of ovarian and deep infiltrating disease and measurement of spontaneous pain behaviors. Future studies must also capitalize on new advances in the wider field of pain medicine to identify more effective treatments for endometriosis-associated pain.

Endometriosis is a complex disorder with a high socio-economic impact. Development of effective novel drug therapies which can be given to women to relieve chronic pain symptoms without side effects such as hormone suppression is urgently required, but progress has been slow. Several different rodent models of 'endometriosis' have been developed, the majority of which mimic aspects of peritoneal disease (e.g. 'lesions' in peritoneal cavity either surgically or spontaneously attached to wall, mesentery, fat). Results obtained using these models have informed our understanding of aetiology including evidence for differential expression of regulatory factors in lesions and impacts on pain perception and fertility. Refinement of these models to ensure reproducibility, extension of models to replicate ovarian and deep disease, complementary in vitro approaches and robust experimental design are all needed to ensure preclinical drug testing results in positive findings in clinical trials and translation for patient benefit.

The existence of endometriosis has been known since at least the nineteenth century, yet the lack of understanding of causes of infertility and therefore inadequate treatment approaches in endometriosis creates a significant challenge in reproductive medicine. Women worldwide suffer not only pain and infertility but also economical, societal, and physiological burdens. Studies of reproductive events in women are difficult to conduct due to a host of confounding personal and environmental factors and ethically limited due to the very nature of working with reproductive tissues and cells, especially embryos. Animal models are a viable adjunct to study mechanisms causing human reproductive anomalies and infertility in endometriosis. This chapter discusses reproductive anomalies causing infertility in endometriosis and well-established animal models which help decipher the problems and lead to heretofore unknown nonsurgical, nonhormonal methods to manage endometriosis in women. In addition, studies of effects of developmental exposure to endometriosis are revealing for the first time, in both female and male offspring, transgenerational subfertility in a rat model providing insights into the familial nature of endometriosis and possible epigenetic involvement.

As a consequence of industrialization, thousands of man-made chemicals have been developed with few undergoing rigorous safety assessment prior to commercial use. Ubiquitous exposure to these compounds, many of which act as endocrine-disrupting chemicals (EDCs), has been suggested to be one factor in the increasing incidence of numerous diseases, including endometriosis. Endometriosis, the presence of endometrial glands and stroma outside the uterus, is a common disorder of reproductive-age women. Although a number of population-based studies have suggested that exposure to environmental EDCs may affect a woman's risk of developing this disease, results of epidemiology assessments are often equivocal. The development of endometriosis is, however, a process occurring over time; thus, a single assessment of toxicant body burden cannot definitively be linked to causation of disease. For this reason, numerous investigators have utilized a variety of rodent models to examine the impact of specific EDCs on the development of experimental endometriosis. These studies identified multiple chemicals capable of influencing physiologic processes necessary for the establishment and/or survival of ectopic tissues in rodents, suggesting that these compounds may also be of concern for women. Importantly, these models serve as useful tools to explore strategies that may prevent adverse outcomes following EDC exposure.

Endometriosis is an enigmatic disease for which we still have a poor understanding on how and why the disease develops. In recent years, miRNAs, small noncoding RNAs which regulate gene expression posttranscriptionally, have been evaluated for their role in endometriosis pathophysiology. This review will provide a brief summary on the role of miRNAs in endometrial physiology and pathophysiology as related to endometriosis. We will then discuss mouse models used in endometriosis research and the incorporation of some of these models in studies which examined the role of miRNAs in endometriosis pathophysiology. We conclude with providing future prospective on the role of mouse models in dissecting the role of miRNAs in endometriosis pathophysiology.

The observation of two precursor groups of the early stem cells (Groups I and II) leads to the realization that a first amount of fetal stem cells (Group I) migrate from the AMG (Aortal-Mesonephric-Gonadal)-region into the aorta and its branching vessels. A second group (Group II) gains quite a new significance during human development. This group presents a specific developmental step which is found only in the human. This continuation of the early development along a different way indicates a general alteration of the stem cell biology. This changed process in the stem cell scene dominates the further development of the human stem cells. It remains unclear where this phylogenetic step first appears. By far not all advanced mammals show this second group of stem cells and their axonal migration. Essentially only primates seem to be involved in this special development.