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Fertility and Sterility Mar 2021Congenital and acquired uterine anomalies are associated with recurrent pregnancy loss (RPL). Relevant congenital Müllerian tract anomalies include unicornuate,... (Review)
Review
Congenital and acquired uterine anomalies are associated with recurrent pregnancy loss (RPL). Relevant congenital Müllerian tract anomalies include unicornuate, bicornuate septate, and arcuate uterus. Recurrent pregnancy loss has also been associated with acquired uterine abnormalities that distort the uterine cavity such as, notably, intrauterine adhesions, polyps, and submucosal myomas. Initial evaluation of women with RPLs should include an assessment of the uterine anatomy. Even if proof of efficacy of surgical management of certain uterine anomalies is often lacking for managing RPLs, surgery should be encouraged in certain circumstances for improving subsequent pregnancy outcome. Uterine anomalies such as uterine septa, endometrial polyps, intrauterine adhesions, and submucosal myomas are the primary surgical indications for managing RPLs.
Topics: Abortion, Habitual; Female; Humans; Hysteroscopy; Pregnancy; Urogenital Abnormalities; Uterus
PubMed: 33712099
DOI: 10.1016/j.fertnstert.2020.12.003 -
Annual Review of Cell and Developmental... Oct 2023The uterine lining (endometrium) regenerates repeatedly over the life span as part of its normal physiology. Substantial portions of the endometrium are shed during... (Review)
Review
The uterine lining (endometrium) regenerates repeatedly over the life span as part of its normal physiology. Substantial portions of the endometrium are shed during childbirth (parturition) and, in some species, menstruation, but the tissue is rapidly rebuilt without scarring, rendering it a powerful model of regeneration in mammals. Nonetheless, following some assaults, including medical procedures and infections, the endometrium fails to regenerate and instead forms scars that may interfere with normal endometrial function and contribute to infertility. Thus, the endometrium provides an exceptional platform to answer a central question of regenerative medicine: Why do some systems regenerate while others scar? Here, we review our current understanding of diverse endometrial disruption events in humans, nonhuman primates, and rodents, and the associated mechanisms of regenerative success and failure. Elucidating the determinants of these disparate repair processes promises insights into fundamental mechanisms of mammalian regeneration with substantial implications for reproductive health.
Topics: Female; Animals; Humans; Endometrium; Uterus; Fibrosis; Mammals
PubMed: 37843929
DOI: 10.1146/annurev-cellbio-011723-021442 -
Frontiers in Immunology 2019The female reproductive tract harbors distinct microbial communities, as in the vagina, cervical canal, uterus, and fallopian tubes. The nature of the vaginal microbiota... (Review)
Review
The female reproductive tract harbors distinct microbial communities, as in the vagina, cervical canal, uterus, and fallopian tubes. The nature of the vaginal microbiota is well-known; in contrast, the upper reproductive tract remains largely unexplored. Alteration in the uterine microbiota, which is dependent on the nutrients and hormones available to the uterus, is likely to play an important role in uterine-related diseases such as hysteromyoma, adenomyosis, and endometriosis. Uterine mucosa is an important tissue barrier whose main function is to offer protection against pathogens and other toxic factors, while maintaining a symbiotic relationship with commensal microbes. These characteristics are shared by all the mucosal tissues; however, the uterine mucosa is unique since it changes cyclically during the menstrual cycle as well as pregnancy. The immune system, besides its role in the defense process, plays crucial roles in reproduction as it ensures local immune tolerance to fetal/paternal antigens, trophoblast invasion, and vascular remodeling. The human endometrium contains a conspicuous number of immune cells, mainly Natural Killers (NK) cells, which are phenotypically distinct from peripheral cytotoxic NK, cells and macrophages. The endometrium also contains few lymphoid aggregates comprising B cell and CD8 T cells. The number and the phenotype of these cells change during the menstrual cycle. It has become evident in recent years that the immune cell phenotype and function can be influenced by microbiota. Immune cells can sense the presence of microbes through their pattern recognition receptors, setting up host-microbe interaction. The microbiota exerts an appropriately controlled defense mechanism by competing for nutrients and mucosal space with pathogens. It has recently been considered that uterus is a non-sterile compartment since it seems to possess its own microbiota. There has been an increasing interest in characterizing the nature of microbial colonization within the uterus and its apparent impact on fertility and pregnancy. This review will examine the potential relationship between the uterine microbiota and the immune cells present in the local environment.
Topics: Adaptive Immunity; Endometrium; Female; Host-Pathogen Interactions; Humans; Immunity; Immunity, Innate; Leukocytes; Lymphocytes; Microbiota; Mucus; Pregnancy; Semen; Uterus
PubMed: 31681281
DOI: 10.3389/fimmu.2019.02387 -
Nature Jul 2023Beginning in the first trimester, fetally derived extravillous trophoblasts (EVTs) invade the uterus and remodel its spiral arteries, transforming them into large,...
Beginning in the first trimester, fetally derived extravillous trophoblasts (EVTs) invade the uterus and remodel its spiral arteries, transforming them into large, dilated blood vessels. Several mechanisms have been proposed to explain how EVTs coordinate with the maternal decidua to promote a tissue microenvironment conducive to spiral artery remodelling (SAR). However, it remains a matter of debate regarding which immune and stromal cells participate in these interactions and how this evolves with respect to gestational age. Here we used a multiomics approach, combining the strengths of spatial proteomics and transcriptomics, to construct a spatiotemporal atlas of the human maternal-fetal interface in the first half of pregnancy. We used multiplexed ion beam imaging by time-of-flight and a 37-plex antibody panel to analyse around 500,000 cells and 588 arteries within intact decidua from 66 individuals between 6 and 20 weeks of gestation, integrating this dataset with co-registered transcriptomics profiles. Gestational age substantially influenced the frequency of maternal immune and stromal cells, with tolerogenic subsets expressing CD206, CD163, TIM-3, galectin-9 and IDO-1 becoming increasingly enriched and colocalized at later time points. By contrast, SAR progression preferentially correlated with EVT invasion and was transcriptionally defined by 78 gene ontology pathways exhibiting distinct monotonic and biphasic trends. Last, we developed an integrated model of SAR whereby invasion is accompanied by the upregulation of pro-angiogenic, immunoregulatory EVT programmes that promote interactions with the vascular endothelium while avoiding the activation of maternal immune cells.
Topics: Female; Humans; Pregnancy; Arteries; Decidua; Pregnancy Trimester, First; Trophoblasts; Uterus; Maternal-Fetal Exchange; Time Factors; Proteomics; Gene Expression Profiling; Datasets as Topic; Gestational Age
PubMed: 37468587
DOI: 10.1038/s41586-023-06298-9 -
Reproductive Sciences (Thousand Oaks,... Jun 2021Impairment of uterine structure and function causes infertility, pregnancy loss, and perinatal complications in humans. Some types of uterine impairments such as... (Review)
Review
Impairment of uterine structure and function causes infertility, pregnancy loss, and perinatal complications in humans. Some types of uterine impairments such as Asherman's syndrome, also known as uterine synechiae, can be treated medically and surgically in a standard clinical setting, but absolute defects of uterine function or structure cannot be cured by conventional approaches. To overcome such hurdles, partial or whole regeneration and reconstruction of the uterus have recently emerged as new therapeutic strategies. Transplantation of the whole uterus into patients with uterine agenesis results in the successful birth of children. However, it remains an experimental treatment with numerous difficulties such as the need for continuous and long-term use of immunosuppressive drugs until a live birth is achieved. Thus, the generation of the uterus by tissue engineering technologies has become an alternative but indispensable therapeutic strategy to treat patients without a functional or well-structured uterus. For the past 20 years, the bioengineering of the uterus has been studied intensively in animal models, providing the basis for clinical applications. A variety of templates and scaffolds made from natural biomaterials, synthetic materials, or decellularized matrices have been characterized to efficiently generate the uterus in a manner similar to the bioengineering of other organs and tissues. The goal of this review is to provide a comprehensive overview and perspectives of uterine bioengineering focusing on the type, preparation, and characteristics of the currently available scaffolds.
Topics: Adult Stem Cells; Animals; Bioengineering; Decellularized Extracellular Matrix; Embryonic Stem Cells; Female; Genital Diseases, Female; Gynatresia; Humans; Induced Pluripotent Stem Cells; Tissue Engineering; Tissue Scaffolds; Urogenital Abnormalities; Uterus
PubMed: 33826100
DOI: 10.1007/s43032-021-00503-8 -
Frontiers in Immunology 2019Natural killer (NK) cells are members of a rapidly expanding family of innate lymphoid cells (ILCs). While most previously studied NK cells were derived from the mouse... (Review)
Review
Natural killer (NK) cells are members of a rapidly expanding family of innate lymphoid cells (ILCs). While most previously studied NK cells were derived from the mouse spleen and circulate in the blood, recently others and we found tissue-resident NK (trNK) cells in many tissues that resemble group 1 ILCs (ILC1s). During pregnancy, NK cells are the most abundant lymphocytes in the uterus at the maternal-fetal interface and are involved in placental vascular remodeling. Prior studies suggested that these uterine NK (uNK) cells are mostly derived from circulating NK cells. However, the murine virgin uterus contains mostly trNK cells and it has been challenging to determine their contribution to uNK cells in pregnancy as well as other potential function(s) of uNK cells due to the dynamic microenvironment in the pregnant uterus. This review focuses on the origins and functions of the heterogeneous populations of uNK cells during the course of murine pregnancy.
Topics: Animals; Female; Humans; Killer Cells, Natural; Mice; Uterus
PubMed: 31118936
DOI: 10.3389/fimmu.2019.00960 -
WormBook : the Online Review of C.... Dec 2005C. elegans hermaphrodites are self-fertile, and their rate and temporal pattern of egg-laying are modulated by diverse environmental cues. Egg-laying behavior has served... (Review)
Review
C. elegans hermaphrodites are self-fertile, and their rate and temporal pattern of egg-laying are modulated by diverse environmental cues. Egg-laying behavior has served as an important phenotypic assay for the genetic dissection of neuronal signal transduction mechanisms. This chapter reviews our current understanding of the neuronal and neurochemical mechanisms underlying the control of egg-laying in C. elegans. The roles of specific neurons in the egg-laying motor circuit, which release multiple neurotransmitters affecting distinct parameters of egg-laying muscle activity, and the possible mechanisms for sensory control of egg-laying behavior, are discussed.
Topics: Animals; Caenorhabditis elegans; Disorders of Sex Development; Female; Oviposition; Uterus; Vulva
PubMed: 18050396
DOI: 10.1895/wormbook.1.38.1 -
Trends in Immunology Mar 2020Uterus transplants (UTxs) have been performed worldwide. Overall frequencies have been low, but globally initiated UTx programs are expected to increase clinical... (Review)
Review
Uterus transplants (UTxs) have been performed worldwide. Overall frequencies have been low, but globally initiated UTx programs are expected to increase clinical implementation. The uterus constitutes a unique immunological environment with specific features of tissue renewal and a receptive endometrium. Decidual immune cells facilitate embryo implantation and placenta development. Although UTx adds to the complexity of immunity during pregnancy and transplantation, the procedure provides a unique clinical and experimental model. We posit that understanding the distinct immunological properties at the interface of the transplanted uterus, the fetus and maternal circulation might provide valuable novel insights while improving outcomes for UTx. Here, we discuss immunological challenges and opportunities of UTx affecting mother, pregnancy and healthy livebirths.
Topics: Embryo Implantation; Female; Fetus; Humans; Organ Transplantation; Pregnancy; Uterus
PubMed: 32109373
DOI: 10.1016/j.it.2020.01.006 -
Revue Medicale de Liege Nov 2022Endometrial osteoid metaplasia is a rare condition characterised by the presence of bone in the uterine cavity. The main symptoms are secondary infertility, cycle...
Endometrial osteoid metaplasia is a rare condition characterised by the presence of bone in the uterine cavity. The main symptoms are secondary infertility, cycle disorders or dysmenorrhea. The discovery can also be fortuitous. Ultrasound and diagnostic hysteroscopy are diagnostic tools while operative hysteroscopy provides treatment. In the vast majority of cases, it is discovered in the aftermath of pregnancy, especially after curettage or miscarriage. There are several theories as to its etiopathogenesis.
Topics: Pregnancy; Female; Humans; Endometrium; Hysteroscopy; Metaplasia; Uterus; Ultrasonography; Infertility, Female
PubMed: 36354220
DOI: No ID Found -
Journal of Materials Science. Materials... May 2017Uterus transplantation is today the only available treatment for absolute uterine factor infertility which is caused by either congenital/surgical uterine absence or... (Review)
Review
Uterus transplantation is today the only available treatment for absolute uterine factor infertility which is caused by either congenital/surgical uterine absence or that a present uterus is non-functioning. Structured animal-based research, from rodents to nonhuman primates, was the scientific basis for a successful introduction of uterus transplantation as a clinical procedure. The patient groups for uterus transplantation, the preclinical research and data from the published human cases will be covered herein. During recent years the concept of bioengineering of organs and tissues has emerged. Creation of a bioengineered uterus is in the initial research state, with experiments performed in rodents. The research that has been performed to create a bioengineered uterus will be summarized. In conclusion, uterus transplantation is now a clinical experimental procedure for treatment of uterine factor infertility. In parallel to the establishment of this combined assisted reproduction technique and transplantation procedure as a routine clinical procedure, we predict that uterus bioengineering will develop further towards introduction within the human setting, but that this process will take several years.
Topics: Animals; Bioengineering; Female; Humans; Infertility, Female; Models, Animal; Pregnancy; Urogenital Abnormalities; Uterus
PubMed: 28357688
DOI: 10.1007/s10856-017-5872-0