Single-cell transcriptome reveals insights into the development and function of the zebrafish ovary

eLife, Journal Year: 2022, Volume and Issue: 11

Published: May 19, 2022

Zebrafish are an established research organism that has made many contributions to our understanding of vertebrate tissue and organ development, yet there still significant gaps in the genes regulate gonad sex, reproduction. Unlike development organs, such as brain heart form during first few days zebrafish gonads do not begin until larval stage (≥5 post-fertilization). Thus, forward genetic screens have identified very required for development. In addition, bulk RNA-sequencing studies identify expressed resolution necessary define minor cell populations may play roles function these organs. To overcome limitations, we used single-cell RNA sequencing determine transcriptomes cells isolated from juvenile ovaries. This resulted profiles 10,658 germ 14,431 somatic cells. Our data represents all developmental stages germline stem early meiotic oocytes. known types, including follicle cells, theca ovarian stromal Further analysis revealed unexpected number subpopulations within broadly defined types. further their functional significance, determined location ovary. Finally, gene knockout experiments foxl2l wnt9b oocyte sex determination and/or differentiation, respectively. results reveal novel insights into function, transcriptome will provide a valuable resource future studies.

Language: Английский

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Age-associated changes in cumulus cells and follicular fluid: the local oocyte microenvironment as a determinant of gamete quality

Biology of Reproduction, Journal Year: 2022, Volume and Issue: 106(2), P. 351 - 365

Published: Jan. 4, 2022

Abstract The ovary is the first organ to age in humans with functional decline evident already women their early 30s. Reproductive aging characterized by a decrease oocyte quantity and quality, which associated an increase infertility, spontaneous abortions, birth defects. also has implications for overall health due decreased endocrinological output. Understanding mechanisms underlying reproductive significant societal as globally are delaying childbearing medical interventions have greatly increased interval between menopause total lifespan. Age-related changes inherent female gamete well-characterized include defects chromosome mitochondria structure, function, regulation. More recently, it been appreciated that extra-follicular ovarian environment may important direct or indirect impacts on developing gamete, age-dependent fibrosis, inflammation, stiffness, oxidative damage. cumulus cells follicular fluid directly surround during its final growth phase within antral follicle represent additional critical local microenvironments. Here we systematically review literature evaluate studies investigated age-related fluid. Our findings demonstrate unique genetic, epigenetic, transcriptomic, proteomic metabolomic alterations, redox status imbalance, apoptosis microenvironment. We propose model of how these interact, explain rapid quality age. limitations published highlight future research frontiers.

Language: Английский

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Biomechanical forces and signals operating in the ovary during folliculogenesis and their dysregulation: implications for fertility

Human Reproduction Update, Journal Year: 2022, Volume and Issue: 29(1), P. 1 - 23

Published: July 20, 2022

Abstract BACKGROUND Folliculogenesis occurs in the highly dynamic environment of ovary. Follicle cyclic recruitment, neo-angiogenesis, spatial displacement, follicle atresia and ovulation stand out as major events resulting from interplay between mechanical forces molecular signals. Morphological functional changes to growing surrounding tissue are required produce oocytes capable supporting preimplantation development blastocyst stage. OBJECTIVE AND RATIONALE This review will summarize ovarian morphological context that contributes growth ovulation, well acquisition oocyte developmental competence. We describe occurring during folliculogenesis extracellular matrix (ECM) vasculature, their influence on properties tissue, and, turn, regulation signal transduction. Also, we outline how dysregulation might be associated with pathologies such polycystic ovary syndrome (PCOS), endometriosis or premature insufficiency (POI). Finally, for each these three pathologies, highlight therapeutic strategies attempting correct altered biomechanical order restore fertility. SEARCH METHODS For area discussed, a systematic bibliographical search was performed, without temporal limits, using PubMed Central, Web Science Scopus engines employing keywords matrix, mechanobiology, biomechanics, angiogenesis signalling pathway combination with: ovary, oogenesis, oocyte, folliculogenesis, follicle, theca, granulosa, cumulus, follicular fluid, corpus luteum, meiosis, competence, preimplantation, syndrome, endometriosis. OUTCOMES Through queries, yielded total 37 368 papers were further selected based our focus mammals specifically, rodents, bovine, equine, ovine, primates human, also trimmed around specific topic review. After elimination duplicates, this selection process resulted 628 papers, which 287 cited manuscript. Among these, 89.2% published past 22 years, while remaining 8.0%, 2.4% 0.3% 1990s, 1980s before, respectively. During occur ECM composition organization that, together vasculature modelling aimed sustain its recruitment growth, maturation enclosed oocyte. These define scenario key cascades Alterations determine impaired decreased potential, observed pathological conditions causes infertility, PCOS, POI. WIDER IMPLICATIONS The knowledge mechanisms rules govern them lay sound basis explain follicles modulated, stimulate insights develop, clinical practice, improve particularly like

Language: Английский

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Making a good egg: human oocyte health, aging, and in vitro development

Physiological Reviews, Journal Year: 2023, Volume and Issue: 103(4), P. 2623 - 2677

Published: May 12, 2023

Mammalian eggs (oocytes) are formed during fetal life and establish associations with somatic cells to form primordial follicles that create a store of germ (the pool). The size this pool is influenced by key events the formation factors influence subsequent activation follicle growth. These regulatory pathways must ensure reserve oocytes within in humans lasts for up 50 years, yet only approximately 0.1% will ever be ovulated rest undergoing degeneration. This review outlines mechanisms govern processes oocyte later growth, ovarian stroma, through ovulation particular reference human oocytes/follicles. In addition, effects aging on female reproductive capacity changes number quality emphasized, both cellular clinical implications discussed. Finally, details current developments culture systems support all stages growth generate mature vitro emerging prospects making new from stem outlined.

Language: Английский

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Beyond apoptosis: evidence of other regulated cell death pathways in the ovary throughout development and life

Human Reproduction Update, Journal Year: 2023, Volume and Issue: 29(4), P. 434 - 456

Published: Feb. 7, 2023

Regulated cell death is a fundamental component of numerous physiological processes; spanning from organogenesis in utero, to normal turnover during adulthood, as well the elimination infected or damaged cells throughout life. Quality control through regulation pathways particularly important germline, which responsible for generation offspring. Women are born with their entire supply germ cells, housed functional units known follicles. Follicles contain an oocyte, specialized somatic granulosa essential oocyte survival. Follicle loss-via regulated death-occurs follicle development and life, can be accelerated following exposure various environmental lifestyle factors. It thought that follicles necessary ensure only best quality oocytes available reproduction.Understanding precise factors involved triggering executing crucial uncovering how endowment initially determined, number maintained puberty, reproductive ovarian ageing women. Apoptosis established homeostasis at all stages However, involvement other ovary less established. This review aims summarize most recent literature on regulators ovary, particular focus non-apoptotic functions discrete life.Comprehensive searches were carried out using PubMed Google Scholar human, animal, cellular studies published until August 2022 search terms: oogenesis, formation, atresia, loss, apoptosis, premature insufficiency, primordial follicles, control, death, autophagy oocytes, necroptosis pyroptosis parthanatos oocytes.Numerous operate mammalian including autophagic necroptosis, pyroptosis. our understanding distinct mediators each type class across different life remains source ongoing investigation. Here, we highlight evidence contribution function. In particular, discuss formation role pyroptosis, response stressors (e.g. oxidative stress).Improved knowledge roles pathway vital development, maintenance function lifespan. information pertinent not endocrine health, fertility women but also enable identification novel preservation targets.

Language: Английский

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Dysregulation of immune response in PCOS organ system

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 5, 2023

Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder affecting women, which can lead to infertility. Infertility, obesity, hirsutism, acne, and irregular menstruation are just a few of issues that PCOS be linked to. has complicated pathophysiology range clinical symptoms. Chronic low-grade inflammation one features PCOS. The inflammatory environment involves immune metabolic disturbances. Numerous organ systems across body, in addition female system, have been affected by pathogenic role immunological dysregulation recent years. Insulin resistance hyperandrogenism associated with cell dysfunction cytokine imbalance. More importantly, obesity also involved PCOS, leading an women Hormone, interactions contribute pathogenesis Hormone imbalance may development autoimmune diseases. aim this review summarize pathophysiological various patients provide new ideas for systemic treatment future.

Language: Английский

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Cellular atlas of the human ovary using morphologically guided spatial transcriptomics and single-cell sequencing

Science Advances, Journal Year: 2024, Volume and Issue: 10(14)

Published: April 5, 2024

The reproductive and endocrine functions of the ovary involve spatially defined interactions among specialized cell populations. Despite ovary’s importance in fertility health, functional attributes ovarian cells are largely uncharacterized. Here, we profiled >18,000 genes 257 regions from ovaries two premenopausal donors to examine units ovary. We also generated single-cell RNA sequencing data for 21,198 three additional identified four major types immune subtypes. Custom selection sampling areas revealed distinct gene activities oocytes, theca, granulosa cells. These contributed panels oocyte-, theca-, granulosa-specific genes, thus expanding knowledge molecular programs driving follicle development. Serial samples around oocytes across cortex medulla uncovered previously unappreciated variation hormone extracellular matrix remodeling activities. This combined spatial atlas serves as a resource future studies rare pathological states

Language: Английский

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Ultrasound Assessment in Polycystic Ovary Syndrome Diagnosis: From Origins to Future Perspectives—A Comprehensive Review

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 453 - 453

Published: Feb. 12, 2025

Background: Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy in women of reproductive age, characterized by a broad spectrum clinical, metabolic, and ultrasound findings. Over time, has evolved into cornerstone for diagnosing polycystic ovarian morphology (PCOM), thanks to advances probe technology, 3D imaging, novel stromal markers. The recent incorporation artificial intelligence (AI) further enhances diagnostic precision reducing operator-related variability. Methods: We conducted narrative review English-language articles PubMed Embase using keywords "PCOS", "polycystic syndrome", "ultrasound", "3D ultrasound", "ovarian stroma". Studies on criteria, imaging modalities, assessment, machine-learning algorithms were prioritized. Additional references identified via citation screening. Results: Conventional 2D remains essential clinical practice, with follicle number per (FNPO) volume (OV) functioning as primary criteria. However, sensitivity specificity values vary significantly depending frequency, cut-off thresholds (≥12, ≥20, or ≥25 follicles), patient characteristics (e.g., adolescence, obesity). Three-dimensional (3D) Doppler techniques refine PCOS diagnosis enabling automated measurements, stromal/ovarian area ratio assessments, evaluation vascular indices correlating strongly hyperandrogenism. Meanwhile, AI-driven analysis emerged promising tool minimizing observer bias validating advanced metrics SA/OA ratio) that may overcome traditional limitations stroma-based Conclusions: continual evolution ultrasound, encompassing higher frequencies, enhancements, now AI-assisted algorithms, expanded our ability characterize PCOM accurately. Nevertheless, challenges such operator dependency inter-observer variability persist despite standardized protocols; integration AI holds promise enhancing accuracy. Future directions should focus robust training datasets, multicenter validation, age-/BMI-specific cut-offs optimize balance between specificity, ultimately facilitating earlier more precise diagnoses.

Language: Английский

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A single-cell atlas of the cycling murine ovary

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Oct. 7, 2022

The estrous cycle is regulated by rhythmic endocrine interactions of the nervous and reproductive systems, which coordinate hormonal ovulatory functions ovary. Folliculogenesis follicle progression require orchestrated response a variety cell types to allow maturation its sequela, ovulation, corpus luteum formation, wound repair. Little known about state dynamics ovary during paracrine factors that help this process. Herein, we used single-cell RNA sequencing evaluate transcriptome >34,000 cells adult mouse describe transcriptional changes occur across normal other states build comprehensive dynamic atlas murine ovarian states.

Language: Английский

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Single‐Cell Atlas of Human Ovaries Reveals The Role Of The Pyroptotic Macrophage in Ovarian Aging

Advanced Science, Journal Year: 2023, Volume and Issue: 11(4)

Published: Nov. 30, 2023

Abstract Female fecundity declines in a nonlinear manner with age during the reproductive years, even as ovulatory cycles continue, which reduces female fertility, disrupts metabolic homeostasis, and eventually induces various chronic diseases. Despite this, aging‐related cellular molecular changes human ovaries that occur these years have not been elucidated. Here, single‐cell RNA sequencing (scRNA‐seq) of is performed from different childbearing ages reveals activation pyroptosis pathway increased age, mainly macrophages. The enrichment pyroptotic macrophages leads to switch tissue‐resident macrophage (TRM)‐involve immunoregulatory microenvironment young monocyte‐derived (MDM)‐involved proinflammatory middle‐aged ovaries. This remolded ovarian immuno‐microenvironment further promotes stromal cell senescence accelerated decline. hypothesis validated series animal experiments using GSDMD‐KO mice. In conclusion, work expands current understanding aging process by illustrating macrophage‐involved immune mechanism, has important implications for development novel strategies delay promote health.

Language: Английский

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