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Animal Genetics Jun 2024Transgenic (Tg) animal technology is one of the growing areas in biology. Various Tg technologies, each with its own advantages and disadvantages, are available for... (Comparative Study)
Comparative Study
Transgenic (Tg) animal technology is one of the growing areas in biology. Various Tg technologies, each with its own advantages and disadvantages, are available for generating Tg animals. These include zygote microinjection, electroporation, viral infection, embryonic stem cell or spermatogonial stem cell-mediated production of Tg animals, sperm-mediated gene transfer (SMGT), and testis-mediated gene transfer (TMGT). However, there are currently no comprehensive studies comparing SMGT and TMGT methods, selecting appropriate gene delivery carriers (such as nanoparticles and liposomes), and determining the optimal route for gene delivery (SMGT and TMGT) for producing Tg animal. Here we aim to provide a comprehensive assessment comparing SMGT and TMGT methods, and to introduce the best carriers and gene transfer methods to sperm and testis to generate Tg animals in different species. From 2010 to 2022, 47 studies on SMGT and 25 studies on TMGT have been conducted. Mice and rats were the most commonly used species in SMGT and TMGT. Regarding the SMGT approach, nanoparticles, streptolysin-O, and virus packaging were found to be the best gene transfer methods for generating Tg mice. In the TMGT method, the best gene transfer methods for generating Tg mice and rats were virus packaging, dimethyl sulfoxide, electroporation, and liposome. Our study has shown that the efficiency of producing Tg animals varies depending on the species, gene carrier, and method of gene transfer.
Topics: Animals; Male; Mice; Rats; Animals, Genetically Modified; Gene Transfer Techniques; Spermatozoa; Testis
PubMed: 38361185
DOI: 10.1111/age.13404 -
Zygote (Cambridge, England) Aug 2023Fertilization failure (FF) and zygotic arrest after ICSI have a huge effect on both patients and clinicians, but both problems are usually unexpected and cannot be... (Review)
Review
Fertilization failure (FF) and zygotic arrest after ICSI have a huge effect on both patients and clinicians, but both problems are usually unexpected and cannot be properly diagnosed. Fortunately, in recent years, gene sequencing has allowed the identification of multiple genetic variants underlying failed ICSI outcomes, but the use of this approach is still far from routine in the fertility clinic. In this systematic review, the genetic variants associated with FF, abnormal fertilization and/or zygotic arrest after ICSI are compiled and analyzed. Forty-seven studies were included. Data from 141 patients carrying 121 genetic variants affecting 16 genes were recorded and analyzed. In total, 27 variants in (in 50 men) and 26 variants in (in 24 women) are two of the factors related to oocyte activation failure that could explain a high percentage of male-related and female-related FF. Additional variants identified were reported in , and (in men), and , , , , , , and (in women). Most of these variants are pathogenic or potentially pathogenic (89/121, 72.9%), as demonstrated by experimental and/or approaches. Most individuals carried bi-allelic variants (89/141, 63.1%), but pathogenic variants in heterozygosity have been identified for and . Clinical treatment options for affected individuals, such as chemical-assisted oocyte activation (AOA) or cRNA injection in the oocyte, are still experimental. In conclusion, a genetic study of known pathogenic variants may help in diagnosing recurrent FF and zygotic arrest and guide patient counselling and future research perspectives.
Topics: Male; Female; Animals; Sperm Injections, Intracytoplasmic; Zygote; Oocytes; Fertilization
PubMed: 37212058
DOI: 10.1017/S096719942300014X -
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 -
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 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 -
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 -
Molecular Human Reproduction Jan 2022Sperm DNA damage is considered a predictive factor for the clinical outcomes of patients undergoing ART. Laboratory evidence suggests that zygotes and developing embryos...
Sperm DNA damage is considered a predictive factor for the clinical outcomes of patients undergoing ART. Laboratory evidence suggests that zygotes and developing embryos have adopted specific response and repair mechanisms to repair DNA damage of paternal origin. We have conducted a systematic review in accordance with guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to identify and review the maternal mechanisms used to respond and repair sperm DNA damage during early embryonic development, how these mechanisms operate and their potential clinical implications. The literature search was conducted in Ovid MEDLINE and Embase databases until May 2021. Out of 6297 articles initially identified, 36 studies were found to be relevant through cross referencing and were fully extracted. The collective evidence in human and animal models indicate that the early embryo has the capacity to repair DNA damage within sperm by activating maternally driven mechanisms throughout embryonic development. However, this capacity is limited and likely declines with age. The link between age and decreased DNA repair capacity could explain decreased oocyte quality in older women, poor reproductive outcomes in idiopathic cases and patients who present high sperm DNA damage. Ultimately, further understanding mechanisms underlying the maternal repair of sperm DNA damage could lead to the development of targeted therapies to decrease sperm DNA damage, improved oocyte quality to combat incoming DNA insults or lead to development of methodologies to identify individual spermatozoa without DNA damage.
Topics: Aged; Animals; DNA Damage; DNA Repair; Embryonic Development; Female; Humans; Male; Oocytes; Pregnancy; Spermatozoa
PubMed: 34954800
DOI: 10.1093/molehr/gaab071 -
Journal of Gynecology Obstetrics and... Oct 2021In female cancer patients anticipating chemotherapy or radiation, oocyte retrieval for fertility should be performed as efficiently as possible to avoid postponing... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
In female cancer patients anticipating chemotherapy or radiation, oocyte retrieval for fertility should be performed as efficiently as possible to avoid postponing cancer treatments. Our objective was to compare clinical outcomes among female cancer patients who underwent a conventional early follicular phase-start ovarian stimulation cycle and those who underwent a random-start ovarian stimulation cycle.
EVIDENCE REVIEW
A systematic review of the literature was performed in accordance with PRISMA guidelines. Medline, Embase.com, Scopus, Cochrane Library, and Clinicaltrials.gov databases were searched to identify all original research published in English through July 2020 on the topic of female cancer patients undergoing ovarian stimulation with a random or conventional start. Studies lacking a comparison group or including women who had already undergone chemotherapy at the time of ovarian stimulation were excluded. The primary author assessed all identified article titles and abstracts, and two independent reviewers assessed full-text articles and extracted data. A meta-analysis with a random-effects model was used to calculate weighted mean differences (WMDs) for outcomes of interest. The primary outcome was the number of mature (meiosis II) oocytes retrieved. Secondary outcomes included duration of stimulation, total dose of gonadotropins, total number of oocytes retrieved, fertilization rate, and number of embryos or zygotes cryopreserved.
RESULTS
A total of 446 articles were screened, and 9 full-text articles (all retrospective cohort or prospective observational) were included for review. Additionally, pooled primary retrospective data from two institutions were included. In total, data from 10 studies including 1653 women were reviewed. Five studies reported the number of embryos cryopreserved, and four reported fertilization rates. Random-start cycles were slightly longer (WMD 0.57 days, 95 % confidence interval [CI] 0.0-1.14 days) and used more total gonadotropins (WMD 248.8 international units, 95 % CI 57.24-440.40) than conventional-start cycles. However, there were no differences in number of mature oocytes retrieved (WMD 0.41 oocytes, 95 % CI -0.84-1.66), number of total oocytes retrieved (WMD 0.90 oocytes, 95 % CI -0.21-2.02), fertilization rates (WMD -0.12, 95 % CI -1.22-0.98), or number of embryos cryopreserved (WMD 0.12 embryos, 95 %CI -0.98-1.22) between random-start and conventional-start cycles. All outcomes except for the parameter "total oocytes retrieved" yielded an I of over 50 %, indicating substantial heterogeneity between studies.
CONCLUSION(S)
Although random-start cycles may entail a longer duration of stimulation and use more total gonadotropins than conventional-start cycles, the absolute differences are small and likely do not significantly affect treatment costs. The similar numbers of mature oocytes retrieved, fertilization rates, and number of embryos cryopreserved in the two start-types suggest that they do not differ in any clinically important ways. Given that random-start cycles can be initiated quickly, they may help facilitate fertility preservation for cancer patients.
Topics: Adult; Cryopreservation; Female; Fertility Preservation; Humans; Neoplasms; Ovulation Induction; Pregnancy
PubMed: 33545413
DOI: 10.1016/j.jogoh.2021.102080 -
American Journal of Medical Genetics.... Jun 2020In this review, we focus on the phenomenon of chimerism and especially microchimerism as one of the currently underexplored explanations for differences in health and...
In this review, we focus on the phenomenon of chimerism and especially microchimerism as one of the currently underexplored explanations for differences in health and behavior. Chimerism is an amalgamation of cells from two or more unique zygotes within a single organism, with microchimerism defined by a minor cell population of <1%. This article first presents an overview of the primary techniques employed to detect and quantify the presence of microchimerism and then reviews empirical studies of chimerism in mammals including primates and humans. In women, male microchimerism, a condition suggested to be the result of fetomaternal exchange in utero, is relatively easily detected by polymerase chain reaction molecular techniques targeting Y-chromosomal markers. Consequently, studies of chimerism in human diseases have largely focused on diseases with a predilection for females including autoimmune diseases, and female cancers. We detail studies of chimerism in human diseases and also discuss some potential implications in behavior. Understanding the prevalence of chimerism and the associated health outcomes will provide invaluable knowledge of human biology and guide novel approaches for treating diseases.
Topics: Autoimmune Diseases; Behavior; Chimerism; Female; Humans; Male; Maternal-Fetal Exchange; Pregnancy
PubMed: 32212323
DOI: 10.1002/ajmg.a.61565 -
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