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Environment International Sep 2023Evidence indicates a link between exposure to ambient air pollution and decreased female fertility. The ability of air pollution particles to reach human ovarian tissue...
Evidence indicates a link between exposure to ambient air pollution and decreased female fertility. The ability of air pollution particles to reach human ovarian tissue and follicles containing the oocytes in various maturation stages has not been studied before. Particulate translocation might be an essential step in explaining reproductive toxicity and assessing associated risks. Here, we analysed the presence of ambient black carbon particles in (i) follicular fluid samples collected during ovum pick-up from 20 women who underwent assisted reproductive technology treatment and (ii) adult human ovarian tissue from 5 individuals. Follicular fluid and ovarian tissue samples were screened for the presence of black carbon particles from ambient air pollution using white light generation by carbonaceous particles under femtosecond pulsed laser illumination. We detected black carbon particles in all follicular fluid (n = 20) and ovarian tissue (n = 5) samples. Black carbon particles from ambient air pollution can reach the ovaries and follicular fluid, directly exposing the ovarian reserve and maturing oocytes. Considering the known link between air pollution and decreased fertility, the impact of such exposure on oocyte quality, ovarian ageing and fertility needs to be clarified urgently.
Topics: Adult; Humans; Female; Ovary; Follicular Fluid; Oocytes; Air Pollution; Carbon
PubMed: 37603992
DOI: 10.1016/j.envint.2023.108141 -
Cell Biology and Toxicology May 2024Premature ovarian failure (POF) affects many adult women less than 40 years of age and leads to infertility. Mesenchymal stem cells-derived small extracellular vesicles...
Premature ovarian failure (POF) affects many adult women less than 40 years of age and leads to infertility. Mesenchymal stem cells-derived small extracellular vesicles (MSCs-sEVs) are attractive candidates for ovarian function restoration and folliculogenesis for POF due to their safety and efficacy, however, the key mediator in MSCs-sEVs that modulates this response and underlying mechanisms remains elusive. Herein, we reported that YB-1 protein was markedly downregulated in vitro and in vivo models of POF induced with HO and CTX respectively, accompanied by granulosa cells (GCs) senescence phenotype. Notably, BMSCs-sEVs transplantation upregulated YB-1, attenuated oxidative damage-induced cellular senescence in GCs, and significantly improved the ovarian function of POF rats, but that was reversed by YB-1 depletion. Moreover, YB-1 showed an obvious decline in serum and GCs in POF patients. Mechanistically, YB-1 as an RNA-binding protein (RBP) physically interacted with a long non-coding RNA, MALAT1, and increased its stability, further, MALAT1 acted as a competing endogenous RNA (ceRNA) to elevate FOXO levels by sequestering miR-211-5p to prevent its degradation, leading to repair of ovarian function. In summary, we demonstrated that BMSCs-sEVs improve ovarian function by releasing YB-1, which mediates MALAT1/miR-211-5p/FOXO axis regulation, providing a possible therapeutic target for patients with POF.
Topics: Animals; Female; Humans; Rats; Cellular Senescence; Exosomes; Forkhead Box Protein O3; Granulosa Cells; Mesenchymal Stem Cells; MicroRNAs; Ovary; Primary Ovarian Insufficiency; Rats, Sprague-Dawley; RNA, Long Noncoding; Y-Box-Binding Protein 1
PubMed: 38700571
DOI: 10.1007/s10565-024-09871-8 -
Overactivation or Apoptosis: Which Mechanisms Affect Chemotherapy-Induced Ovarian Reserve Depletion?International Journal of Molecular... Nov 2023Dormant primordial follicles (PMF), which constitute the ovarian reserve, are recruited continuously into the cohort of growing follicles in the ovary throughout female... (Review)
Review
Dormant primordial follicles (PMF), which constitute the ovarian reserve, are recruited continuously into the cohort of growing follicles in the ovary throughout female reproductive life. Gonadotoxic chemotherapy was shown to diminish the ovarian reserve pool, to destroy growing follicle population, and to cause premature ovarian insufficiency (POI). Three primary mechanisms have been proposed to account for this chemotherapy-induced PMF depletion: either indirectly via over-recruitment of PMF, by stromal damage, or through direct toxicity effects on PMF. Preventative pharmacological agents intervening in these ovotoxic mechanisms may be ideal candidates for fertility preservation (FP). This manuscript reviews the mechanisms that disrupt follicle dormancy causing depletion of the ovarian reserve. It describes the most widely studied experimental inhibitors that have been deployed in attempts to counteract these affects and prevent follicle depletion.
Topics: Humans; Female; Ovarian Reserve; Ovarian Follicle; Ovary; Apoptosis; Antineoplastic Agents
PubMed: 38003481
DOI: 10.3390/ijms242216291 -
Zoology (Jena, Germany) Oct 2023Ovaries in earthworms belonging to the family Megascolecidae are paired structures attached to the septum in the anterior part of the XIII segment. They are fan to...
Ovaries in earthworms belonging to the family Megascolecidae are paired structures attached to the septum in the anterior part of the XIII segment. They are fan to rosette shaped with numerous rows of growing oocytes, known as egg strings, radiating from the ovary center towards the segmental cavity. The histological and ultrastructural ovary organization in megascolecids and the course of oogenesis remain unknown. The paper presents the results of light and electron microscopy analyses of ovaries in six megascolecid species, three from the genus Amynthas and three from Metaphire. Both parthenogenetic and sexually reproducing species were included in the study. The organization and ultrastructure of ovaries in all studied species are broadly similar. Considering the histological organization of ovaries, they could be divided into two zones. Zone I (proximal, close to the connection with the septum) is tightly packed with germline and somatic cells. Germ cells are interconnected via intercellular bridges and thin strands of the central cytoplasm (known as cytophore) and form syncytial cysts. Cysts unite oogonia, early meiotic cells (till diplotene), and clustering cells develop synchronously. During diplotene, interconnected cells lose developmental synchrony; most probably, one cell per cyst grows faster than others, detaches from the cysts, and becomes an oocyte. The remaining cells grow slightly and are still interconnected via the thin and reticular cytophore; these cells are considered nurse cells. Zone II has a form of egg strings where growing oocytes are isolated one from another by thin somatic cells and form short cords. We present the ultrastructural details of germline and somatic cells. We propose the term "Amynthas" type of ovaries for this ovary organization. We suppose that such ovaries are characteristic of other megascolecids and related families.
Topics: Humans; Female; Animals; Ovary; Oligochaeta; Oocytes; Oogenesis; Germ Cells
PubMed: 37586295
DOI: 10.1016/j.zool.2023.126109 -
Journal of Biomedical Science Mar 2024The mammalian ovary is a unique organ that displays a distinctive feature of cyclic changes throughout the entire reproductive period. The estrous/menstrual cycles are... (Review)
Review
BACKGROUND
The mammalian ovary is a unique organ that displays a distinctive feature of cyclic changes throughout the entire reproductive period. The estrous/menstrual cycles are associated with drastic functional and morphological rearrangements of ovarian tissue, including follicular development and degeneration, and the formation and subsequent atrophy of the corpus luteum. The flawless execution of these reiterative processes is impossible without the involvement of programmed cell death (PCD).
MAIN TEXT
PCD is crucial for efficient and careful clearance of excessive, depleted, or obsolete ovarian structures for ovarian cycling. Moreover, PCD facilitates selection of high-quality oocytes and formation of the ovarian reserve during embryonic and juvenile development. Disruption of PCD regulation can heavily impact the ovarian functions and is associated with various pathologies, from a moderate decrease in fertility to severe hormonal disturbance, complete loss of reproductive function, and tumorigenesis. This comprehensive review aims to provide updated information on the role of PCD in various processes occurring in normal and pathologic ovaries. Three major events of PCD in the ovary-progenitor germ cell depletion, follicular atresia, and corpus luteum degradation-are described, alongside the detailed information on molecular regulation of these processes, highlighting the contribution of apoptosis, autophagy, necroptosis, and ferroptosis. Ultimately, the current knowledge of PCD aberrations associated with pathologies, such as polycystic ovarian syndrome, premature ovarian insufficiency, and tumors of ovarian origin, is outlined.
CONCLUSION
PCD is an essential element in ovarian development, functions and pathologies. A thorough understanding of molecular mechanisms regulating PCD events is required for future advances in the diagnosis and management of various disorders of the ovary and the female reproductive system in general.
Topics: Animals; Female; Humans; Ovary; Follicular Atresia; Apoptosis; Cell Death; Oocytes; Mammals
PubMed: 38509545
DOI: 10.1186/s12929-024-01017-6 -
Environmental Pollution (Barking, Essex... Aug 2023Bisphenol (BP) structural analogues of BPA are widely used. Previous studies showed similar effects of BPA and BPS on reproduction in several species including human. We...
Bisphenol (BP) structural analogues of BPA are widely used. Previous studies showed similar effects of BPA and BPS on reproduction in several species including human. We hypothesised that the similar effects of several bisphenols (BPs) could accumulate in granulosa cells (GCs) and affects steroidogenesis. This study investigated the effects of seven BP analogues and their equimolar cocktail on human granulosa cells (hGC) and assessed BPA, BPS, BPF and BPAF level exposures in the follicular fluid of 277 women undergoing Assisted Reproductive Technology. The hGCs were recovered after women oocyte punctures and treated with the seven BP analogues (BPS, BPA, BPAF, BPF, BPAP, BPE and BPB) or their equimolar cocktail of 7 × 1.43 or 7 × 7.14 μM for each of the seven BPs, the sum of BPs reaching 10 ("∑BPs 10 μM"), or 50 μM ("∑BPs 50 μM"), respectively. Oestradiol and progesterone secretion, cell proliferation, viability and expression of steroidogenic enzymes were investigated. Progesterone secretion was decreased by 6 BPs 10 μM and the cocktail "∑BPs 10 μM", (-17.8 to -41.3%) and by all seven BPs 50 μM and "∑BPs 50 μM" (-21.8 to -84.2%). Oestradiol secretion was decreased only by 50 μM BPAF and BPAP (-37.8% and -44%, respectively), with corresponding decreases in CYP17A1 and CYP19A1 gene expression. Cellular proliferation was decreased after treatment with 50 μM BPAF (-32.2%), BPAP (-29%), BPB (-24%) and the equimolar cocktail "∑BPs 50 μM" (-33.1%). BPB (50 μM) and the cocktail "∑BPs 50 μM" increased HSD3B2 mRNA expression. At least one BP was detected in 64 of 277 (23.1%) women follicular fluids. Similar effects of the seven BPs or their cocktail were observed on progesterone secretion and/or on cell proliferation, suggesting cumulative effects of BPs. Our results highlight the urge to consider all BPs simultaneously and to further investigate the potential additive or synergistic effects of several BPs.
Topics: Humans; Female; Male; Progesterone; Benzhydryl Compounds; Granulosa Cells; Estradiol
PubMed: 37182577
DOI: 10.1016/j.envpol.2023.121818 -
International Journal of Molecular... Jul 2023Exosomal regulation is intimately involved in key cellular processes, such as migration, proliferation, and adhesion. By participating in the regulation of basic...
Exosomal regulation is intimately involved in key cellular processes, such as migration, proliferation, and adhesion. By participating in the regulation of basic mechanisms, extracellular vesicles are important in intercellular signaling and the functioning of the mammalian reproductive system. The complexity of intercellular interactions in the ovarian follicle is also based on multilevel intercellular signaling, including the mechanisms involving cadherins, integrins, and the extracellular matrix. The processes in the ovary leading to the formation of a fertilization-ready oocyte are extremely complex at the molecular level and depend on the oocyte's ongoing relationship with granulosa cells. An analysis of gene expression from material obtained from a primary in vitro culture of porcine granulosa cells was employed using microarray technology. Genes with the highest expression (LIPG, HSD3B1, CLIP4, LOX, ANKRD1, FMOD, SHAS2, TAGLN, ITGA8, MXRA5, and NEXN) and the lowest expression levels (DAPL1, HSD17B1, SNX31, FST, NEBL, CXCL10, RGS2, MAL2, IHH, and TRIB2) were selected for further analysis. The gene expression results obtained from the microarrays were validated using quantitative RT-qPCR. Exosomes may play important roles regarding intercellular signaling between granulosa cells. Therefore, exosomes may have significant applications in regenerative medicine, targeted therapy, and assisted reproduction technologies.
Topics: Female; Swine; Animals; Granulosa Cells; Ovarian Follicle; Oocytes; Ovary; Cell Proliferation; Mammals
PubMed: 37511632
DOI: 10.3390/ijms241411873 -
Proceedings of the National Academy of... Jan 2024Ovulation is essential for reproductive success, yet the underlying cellular and molecular mechanisms are far from clear. Here, we applied high-resolution spatiotemporal...
Ovulation is essential for reproductive success, yet the underlying cellular and molecular mechanisms are far from clear. Here, we applied high-resolution spatiotemporal transcriptomics to map out cell type- and ovulation stage-specific molecular programs as function of time during follicle maturation and ovulation in mice. Our analysis revealed dynamic molecular transitions within granulosa cell types that occur in tight coordination with mesenchymal cell proliferation. We identified molecular markers for the emerging cumulus cell fate during the preantral-to-antral transition. We describe transcriptional programs that respond rapidly to ovulation stimulation and those associated with follicle rupture, highlighting the prominent roles of apoptotic and metabolic pathways during the final stages of follicle maturation. We further report stage-specific oocyte-cumulus cell interactions and diverging molecular differentiation in follicles approaching ovulation. Collectively, this study provides insights into the cellular and molecular processes that regulate mouse ovarian follicle maturation and ovulation with important implications for advancing therapeutic strategies in reproductive medicine.
Topics: Female; Animals; Mice; Ovary; Ovulation; Ovarian Follicle; Reproduction; Granulosa Cells; Ascomycota
PubMed: 38252830
DOI: 10.1073/pnas.2317418121 -
Reproductive Biology and Endocrinology... Dec 2023Survival rates of young women undergoing cancer treatment have substantially improved, with a focus on post-treatment quality of life. Ovarian tissue transplantation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Survival rates of young women undergoing cancer treatment have substantially improved, with a focus on post-treatment quality of life. Ovarian tissue transplantation (OTT) is a viable option to preserve fertility; however, there is no consensus on the optimal transplantation site. Most studies on OTT are nonrandomized controlled trials with limited sample sizes and uncontrolled statistical analyses, leaving the question of which transplant site yields the highest chance of achieving a live birth unanswered.
OBJECTIVE
This meta-analysis aimed to assess the effect of different ovarian transplant sites on postoperative reproductive outcomes.
METHODS
We adhered to the PRISMA Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Systematic searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Library from inception to September 17, 2023. The inclusion criteria were as follows: (1) women who underwent OTT with a desire for future childbirth, and (2) reports of specific transplant sites and corresponding pregnancy outcomes. The exclusion criteria included the inability to isolate or extract relevant outcome data, case reports, non-original or duplicate data, and articles not written in English.
RESULTS
Twelve studies (201 women) were included in the meta-analysis of cumulative live birth rates (CLBR) after OTT. The CLBR, which encompasses both spontaneous pregnancies and those achieved through assisted reproductive technology (ART) following OTT to the ovarian site, was 21% (95% CI: 6-40, I: 52.81%, random effect). For transplantation to the pelvic site, the live birth rate was 30% (95% CI: 20-40, I: 0.00%, fixed effect). Combining transplantation to both the pelvic and ovarian sites resulted in a live birth rate of 23% (95% CI: 11-36, I: 0.00%, fixed effect). Notably, heterotopic OTT yielded a live birth rate of 3% (95% CI: 0-17, I: 0.00%, fixed effect).
CONCLUSION
Pregnancy outcomes were not significantly different after orthotopic ovarian transplantation, and pregnancy and live birth rates after orthotopic OTT were significantly higher than those after ectopic transplantation.
REGISTRATION NUMBER
INPLASY202390008.
Topics: Pregnancy; Female; Humans; Quality of Life; Ovary; Reproductive Techniques, Assisted; Pregnancy Outcome; Pregnancy, Multiple; Live Birth; Pregnancy Rate
PubMed: 38087312
DOI: 10.1186/s12958-023-01167-6 -
Journal of Translational Medicine Apr 2024Polycystic ovary syndrome (PCOS) is an endocrinological and metabolic disorder that can lead to female infertility. Lipid metabolomics and proteomics are the new...
BACKGROUND
Polycystic ovary syndrome (PCOS) is an endocrinological and metabolic disorder that can lead to female infertility. Lipid metabolomics and proteomics are the new disciplines in systems biology aimed to discover metabolic pathway changes in diseases and diagnosis of biomarkers. This study aims to reveal the features of PCOS to explore its pathogenesis at the protein and metabolic level.
METHODS
We collected follicular fluid samples and granulosa cells of women with PCOS and normal women who underwent in vitro fertilization(IVF) and embryo transfer were recruited. The samples were for the lipidomic study and the proteomic study based on the latest metabolomics and proteomics research platform.
RESULTS
Lipid metabolomic analysis revealed abnormal metabolism of glycerides, glycerophospholipids, and sphingomyelin in the FF of PCOS. Differential lipids were strongly linked with the rate of high-quality embryos. In total, 144 differentially expressed proteins were screened in ovarian granulosa cells in women with PCOS compared to controls. Go functional enrichment analysis showed that differential proteins were associated with blood coagulation and lead to follicular development disorders.
CONCLUSION
The results showed that the differential lipid metabolites and proteins in PCOS were closely related to follicle quality,which can be potential biomarkers for oocyte maturation and ART outcomes.
Topics: Female; Humans; Polycystic Ovary Syndrome; Follicular Fluid; Proteomics; Biomarkers; Lipids
PubMed: 38632610
DOI: 10.1186/s12967-024-05167-x