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Human Reproduction Update Nov 2022To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones...
BACKGROUND
To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones produced by the ovaries. Mature oocytes may be fertilized in the fallopian tubes, and the resulting zygote is transported toward the uterus, where it can implant and continue developing. The cervix acts as a physical barrier to protect the fetus throughout pregnancy, and the vagina acts as a birth canal (involving uterine and cervix mechanisms) and facilitates copulation. Fertility can be compromised by pathologies that affect any of these organs or processes, and therefore, being able to accurately model them or restore their function is of paramount importance in applied and translational research. However, innate differences in human and animal model reproductive tracts, and the static nature of 2D cell/tissue culture techniques, necessitate continued research and development of dynamic and more complex in vitro platforms, ex vivo approaches and in vivo therapies to study and support reproductive biology. To meet this need, bioengineering is propelling the research on female reproduction into a new dimension through a wide range of potential applications and preclinical models, and the burgeoning number and variety of studies makes for a rapidly changing state of the field.
OBJECTIVE AND RATIONALE
This review aims to summarize the mounting evidence on bioengineering strategies, platforms and therapies currently available and under development in the context of female reproductive medicine, in order to further understand female reproductive biology and provide new options for fertility restoration. Specifically, techniques used in, or for, the uterus (endometrium and myometrium), ovary, fallopian tubes, cervix and vagina will be discussed.
SEARCH METHODS
A systematic search of full-text articles available in PubMed and Embase databases was conducted to identify relevant studies published between January 2000 and September 2021. The search terms included: bioengineering, reproduction, artificial, biomaterial, microfluidic, bioprinting, organoid, hydrogel, scaffold, uterus, endometrium, ovary, fallopian tubes, oviduct, cervix, vagina, endometriosis, adenomyosis, uterine fibroids, chlamydia, Asherman's syndrome, intrauterine adhesions, uterine polyps, polycystic ovary syndrome and primary ovarian insufficiency. Additional studies were identified by manually searching the references of the selected articles and of complementary reviews. Eligibility criteria included original, rigorous and accessible peer-reviewed work, published in English, on female reproductive bioengineering techniques in preclinical (in vitro/in vivo/ex vivo) and/or clinical testing phases.
OUTCOMES
Out of the 10 390 records identified, 312 studies were included for systematic review. Owing to inconsistencies in the study measurements and designs, the findings were assessed qualitatively rather than by meta-analysis. Hydrogels and scaffolds were commonly applied in various bioengineering-related studies of the female reproductive tract. Emerging technologies, such as organoids and bioprinting, offered personalized diagnoses and alternative treatment options, respectively. Promising microfluidic systems combining various bioengineering approaches have also shown translational value.
WIDER IMPLICATIONS
The complexity of the molecular, endocrine and tissue-level interactions regulating female reproduction present challenges for bioengineering approaches to replace female reproductive organs. However, interdisciplinary work is providing valuable insight into the physicochemical properties necessary for reproductive biological processes to occur. Defining the landscape of reproductive bioengineering technologies currently available and under development for women can provide alternative models for toxicology/drug testing, ex vivo fertility options, clinical therapies and a basis for future organ regeneration studies.
Topics: Animals; Female; Humans; Pregnancy; Bioengineering; Embryo Implantation; Genitalia, Female; Reproduction; Uterus
PubMed: 35652272
DOI: 10.1093/humupd/dmac025 -
Journal of Assisted Reproduction and... Jun 2023The storage and release of calcium ions (Ca2 +) in oocyte maturation and fertilization are particularly noteworthy features of the endoplasmic reticulum (ER). The ER... (Review)
Review
The storage and release of calcium ions (Ca2 +) in oocyte maturation and fertilization are particularly noteworthy features of the endoplasmic reticulum (ER). The ER is the largest organelle in the cell composed of rough ER, smooth ER, and nuclear envelope, and is the main site of protein synthesis, transport and folding, and lipid and steroid synthesis. An appropriate calcium signaling response can initiate oocyte development and embryogenesis, and the ER is the central link that initiates calcium signaling. The transition from immature oocytes to zygotes also requires many coordinated organelle reorganizations and changes. Therefore, the purpose of this review is to generalize information on the function, structure, interaction with other organelles, and spatiotemporal localization of the ER in mammalian oocytes. Mechanisms related to maintaining ER homeostasis have been extensively studied in recent years. Resolving ER stress through the unfolded protein response (UPR) is one of them. We combined the clinical problems caused by the ER in in vitro maturation (IVM), and the mechanisms of ER have been identified by single-cell RNA-seq. This article systematically reviews the functions of ER and provides a reference for assisted reproductive technology (ART) research.
Topics: Animals; Oocytes; Unfolded Protein Response; Endoplasmic Reticulum Stress; Oogenesis; Endoplasmic Reticulum; Mammals
PubMed: 37171741
DOI: 10.1007/s10815-023-02782-3 -
Journal of Reproductive Immunology Aug 2022The fallopian tubes (FT) play a key role in fertility by facilitating the movement of gametes to promote fertilisation and, subsequently, passage of the zygote for... (Review)
Review
The fallopian tubes (FT) play a key role in fertility by facilitating the movement of gametes to promote fertilisation and, subsequently, passage of the zygote for implantation. Histologically, the FT mucosa consists of three main cell types: secretory, ciliated and peg cells. In addition, several studies have reported the presence of immune cells. This systematic review aims to present a comprehensive analysis of the immune cell populations in the human FT, both in health and benign pathology, to promote a better understanding of tubal pathologies and their influence on infertility. A comprehensive literature search was conducted across five databases and augmented with manual citation chaining. Forty-two eligible studies were selected in accordance with PRISMA guidelines. Following screening, risk of bias assessments were conducted, data extracted and the findings presented thematically. T lymphocytes, predominantly CD8 T cells, represent the most abundant immune cell population within the healthy FT, with B lymphocytes, macrophages, NK cells and dendritic cells also localised to the tubal mucosa. There is evidence to suggest that lymphocyte and macrophage populations are susceptible to changes in the concentration of reproductive hormones. Tubal ectopic pregnancy, salpingitis, hydrosalpinx and endometriosis are all characterised by an increased population of macrophages in comparison to healthy FT. However, given the inconsistent evidence presented between studies, and the lack of studies examining all immune cell subtypes in tubal pathologies, only limited conclusions can be formulated on pathology-specific immune cell populations, and further research is required for validation.
Topics: CD8-Positive T-Lymphocytes; Fallopian Tubes; Female; Humans; Mucous Membrane; Pregnancy; Pregnancy, Tubal; Salpingitis
PubMed: 35644062
DOI: 10.1016/j.jri.2022.103646 -
Clinical Gastroenterology and... Aug 2020Somatic mosaicism, in which variants arise post-zygotically and are therefore not present in all cells in the body, may be an underestimated cause of colorectal cancer... (Review)
Review
BACKGROUND & AIMS
Somatic mosaicism, in which variants arise post-zygotically and are therefore not present in all cells in the body, may be an underestimated cause of colorectal cancer (CRC) and polyposis syndromes. We performed a systematic review to provide a comprehensive overview of somatic mosaicism in patients with CRC and polyposis syndromes.
METHODS
We searched PubMed through March 2018 to identify reports of mosaicism in patients with CRC or polyposis syndromes. We divided the final set of studies into 3 subgroups describing APC mosaicism, mosaicism in other CRC susceptibility genes, and epigenetic mosaicism.
RESULTS
Of the 232 articles identified in our systematic search, 46 met the criteria for further analysis. Of these, 35 studies described mosaic variants or epimutations in patients with CRC or polyposis syndromes. Nineteen studies described APC mosaicism, comprising a total of 57 patients. Six described mosaicism in genes associated with familial CRC syndromes, such as Lynch and Cowden syndromes. Ten studies described epigenetic mosaicism, sometimes resulting from a germline variant (such as deletion of EPCAM).
CONCLUSIONS
We found that somatic mosaicism is underdiagnosed but critical for determining the clinical management of patients with de novo polyposis who possibly carry mosaic APC variants, and present a decision tree for the clinical management of these patients. Mosaicism in genes associated with susceptibility to CRC contributes to development of other familial CRC syndromes. Heritable epigenetic mosaicism is likely underestimated and could have a dominant pattern of inheritance. However, the inheritance of primary mosaic epimutations, without an underlying genetic cause, is complex and not fully understood.
Topics: Adenomatous Polyposis Coli; Colorectal Neoplasms; Genetic Predisposition to Disease; Humans; Mosaicism; Neoplastic Syndromes, Hereditary
PubMed: 32147591
DOI: 10.1016/j.cgh.2020.02.049 -
Frontiers in Plant Science 2022Plants have amazing regenerative properties with single somatic cells, or groups of cells able to give rise to fully formed plants. One means of regeneration is somatic...
Plants have amazing regenerative properties with single somatic cells, or groups of cells able to give rise to fully formed plants. One means of regeneration is somatic embryogenesis, by which an embryonic structure is formed that "converts" into a plantlet. Somatic embryogenesis has been used as a model for zygotic processes that are buried within layers of maternal tissues. Understanding mechanisms of somatic embryo induction and development are important as a more accessible model for seed development. We rely on seed development not only for most of our caloric intake, but also as a delivery system for engineered crops to meet agricultural challenges. Regeneration of transformed cells is needed for this applied work as well as basic research to understand gene function. Here we focus on a MADS-domain transcription factor, AGAMOUS-Like15 (AGL15) that shows a positive correlation between accumulation levels and capacity for somatic embryogenesis. We relate AGL15 function to other transcription factors, hormones, and epigenetic modifiers involved in somatic embryo development.
PubMed: 35419012
DOI: 10.3389/fpls.2022.861556