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Nature Communications Jul 2023The hard tick, Ixodes ricinus, a main Lyme disease vector, harbors an intracellular bacterial endosymbiont. Midichloria mitochondrii is maternally inherited and resides...
The hard tick, Ixodes ricinus, a main Lyme disease vector, harbors an intracellular bacterial endosymbiont. Midichloria mitochondrii is maternally inherited and resides in the mitochondria of I. ricinus oocytes, but the consequences of this endosymbiosis are not well understood. Here, we provide 3D images of wild-type and aposymbiotic I. ricinus oocytes generated with focused ion beam-scanning electron microscopy. Quantitative image analyses of endosymbionts and oocyte mitochondria at different maturation stages show that the populations of both mitochondrion-associated bacteria and bacterium-hosting mitochondria increase upon vitellogenisation, and that mitochondria can host multiple bacteria in later stages. Three-dimensional reconstructions show symbiosis-dependent morphologies of mitochondria and demonstrate complete M. mitochondrii inclusion inside a mitochondrion. Cytoplasmic endosymbiont located close to mitochondria are not oriented towards the mitochondria, suggesting that bacterial recolonization is unlikely. We further demonstrate individual globular-shaped mitochondria in the wild type oocytes, while aposymbiotic oocytes only contain a mitochondrial network. In summary, our study suggests that M. mitochondrii modulates mitochondrial fragmentation in oogenesis possibly affecting organelle function and ensuring its presence over generations.
Topics: Imaging, Three-Dimensional; Rickettsiales; Oocytes; Mitochondria; Cytoplasm
PubMed: 37438329
DOI: 10.1038/s41467-023-39758-x -
Human Reproduction (Oxford, England) Nov 2023Is the abundance of certain biochemical compounds in human cumulus cells (CCs) related to oocyte quality?
STUDY QUESTION
Is the abundance of certain biochemical compounds in human cumulus cells (CCs) related to oocyte quality?
SUMMARY ANSWER
Malonate, 5-oxyproline, and erythronate were positively associated with pregnancy potential.
WHAT IS KNOWN ALREADY
CCs are removed and discarded prior to ICSI, thereby constituting an interesting biological material on which to perform molecular analysis aimed to predict oocyte developmental competence. Mitochondrial DNA content and transcriptional analyses in CC have been shown to provide a poor predictive value of oocyte competence, but the untargeted analysis of biochemical compounds (metabolomics) has been unexplored.
STUDY DESIGN, SIZE, DURATION
CCs were obtained from three groups of cumulus-oocyte complexes (COCs) of known developmental potential: oocytes not developing to blastocyst following ICSI (Bl-); oocytes developing to blastocyst but failing to establish pregnancy following embryo transfer (P-); and oocytes developing to blastocyst able to establish a pregnancy (P+). Metabolomics analyses were performed on 12 samples per group, each sample comprising the CC recovered from a single COC.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Human CC samples were obtained from IVF treatments. Only unfrozen oocytes and embryos not submitted to preimplantation genetic testing were included in the analysis. Metabolomics analysis was performed by ultra-high performance liquid chromatography-tandem mass spectroscopy.
MAIN RESULTS AND THE ROLE OF CHANCE
The analysis identified 98 compounds, five of which were differentially abundant (P < 0.05) between groups: asparagine, proline, and malonate were less abundant in P- compared to Bl-, malonate and 5-oxoproline were less abundant in P- group compared to P+, and erythronate was less abundant in Bl- group compared to P+. No significant association between the abundance of the compounds identified and donor age or BMI was noted.
LIMITATIONS, REASONS FOR CAUTION
Data dispersion and the lack of coherence between developmental groups preclude the direct use of metabolic markers in clinical practice, where the uterine environment plays a major role in pregnancy outcome. The abundance of other compounds not detected by the analysis may be associated with oocyte competence. As donors were lean (only two with BMI > 30 kg/m2) and young (<34 years old), a possible effect of obesity or advanced age on the CC metabolome could not be determined.
WIDER IMPLICATIONS OF THE FINDINGS
The abundance of malonate, 5-oxyproline, and erythronate in CC was significantly higher in COCs ultimately establishing pregnancy, providing clues on the pathways required for oocyte competence. The untargeted analysis uncovered the presence of compounds that were not expected in CC, such as β-citrylglutamate and the neurotransmitter N-acetyl-aspartyl-glutamate, which may play roles in chromatin remodeling and signaling, respectively.
STUDY FUNDING/COMPETING INTEREST(S)
Research was supported by the Industrial Doctorate Project IND2017/BIO-7748 funded by Madrid Region Government. The authors declare no competing interest.
TRIAL REGISTRATION NUMBER
N/A.
Topics: Female; Humans; Pregnancy; Adult; Cumulus Cells; Hydroxyproline; Oocytes; Oogenesis; Malonates
PubMed: 37697661
DOI: 10.1093/humrep/dead181 -
The EMBO Journal Dec 2023In most metazoans, centrioles are lost during oogenesis, ensuring that the zygote is endowed with the correct number of two centrioles, which are paternally contributed....
In most metazoans, centrioles are lost during oogenesis, ensuring that the zygote is endowed with the correct number of two centrioles, which are paternally contributed. How centriole architecture is dismantled during oogenesis is not understood. Here, we analyze with unprecedent detail the ultrastructural and molecular changes during oogenesis centriole elimination in Caenorhabditis elegans. Centriole elimination begins with loss of the so-called central tube and organelle widening, followed by microtubule disassembly. The resulting cluster of centriolar proteins then disappears gradually, usually moving in a microtubule- and dynein-dependent manner to the plasma membrane. Our analysis indicates that neither Polo-like kinases nor the PCM, which modulate oogenesis centriole elimination in Drosophila, do so in C. elegans. Furthermore, we demonstrate that the central tube protein SAS-1 normally departs initially from the organelle, which loses integrity earlier in sas-1 mutants. Overall, our work provides novel mechanistic insights regarding the fundamental process of oogenesis centriole elimination.
Topics: Animals; Caenorhabditis elegans; Centrioles; Caenorhabditis elegans Proteins; Microtubules; Drosophila; Oogenesis; Cell Cycle Proteins
PubMed: 37987153
DOI: 10.15252/embj.2023115076 -
European Journal of Medical Research Jul 2023Polycystic ovary syndrome (PCOS) women have high incidences of dyslipidemia, obesity, impaired glucose tolerance (IGT), diabetes, and insulin resistance (IR) and are...
Adiposity and lipid metabolism indicators mediate the adverse effect of glucose metabolism indicators on oogenesis and embryogenesis in PCOS women undergoing IVF/ICSI cycles.
BACKGROUND
Polycystic ovary syndrome (PCOS) women have high incidences of dyslipidemia, obesity, impaired glucose tolerance (IGT), diabetes, and insulin resistance (IR) and are fragile to female infertility. Obesity and dyslipidemia may be the intermediate biological mechanism for the associations between glucose metabolism dysfunction and abnormal oogenesis and embryogenesis.
METHODS
This retrospective cohort study was performed at a university-affiliated reproductive center. A total of 917 PCOS women aged between 20 and 45 undergoing their first IVF/ICSI embryo transfer cycles from January 2018 to December 2020 were involved. Associations between glucose metabolism indicators, adiposity and lipid metabolism indicators, and IVF/ICSI outcomes were explored using multivariable generalized linear models. Mediation analyses were further performed to examine the potential mediation role of adiposity and lipid metabolism indicators.
RESULTS
Significant dose-dependent relationships were found between glucose metabolism indicators and IVF/ICSI early reproductive outcomes and between glucose metabolism indicators and adiposity and lipid metabolism indicators (all P < 0.05). Also, we found significant dose-dependent relationships between adiposity and lipid metabolism indicators and IVF/ICSI early reproductive outcomes (all P < 0.05). The mediation analysis indicated that elevated FPG, 2hPG, FPI, 2hPI, HbA1c, and HOMA2-IR were significantly associated with decreased retrieved oocyte count, MII oocyte count, normally fertilized zygote count, normally cleaved embryo count, high-quality embryo count, or blastocyst formation count after controlling for adiposity and lipid metabolism indicators. Serum TG mediated 6.0-31.0% of the associations; serum TC mediated 6.1-10.8% of the associations; serum HDL-C mediated 9.4-43.6% of the associations; serum LDL-C mediated 4.2-18.2% of the associations; and BMI mediated 26.7-97.7% of the associations.
CONCLUSIONS
Adiposity and lipid metabolism indicators (i.e., serum TG, serum TC, serum HDL-C, serum LDL-C, and BMI) are significant mediators of the effect of glucose metabolism indicators on IVF/ICSI early reproductive outcomes in PCOS women, indicating the importance of preconception glucose and lipid management and the dynamic equilibrium of glucose and lipid metabolism in PCOS women.
Topics: Humans; Female; Polycystic Ovary Syndrome; Sperm Injections, Intracytoplasmic; Fertilization in Vitro; Retrospective Studies; Adiposity; Cholesterol, LDL; Lipid Metabolism; Embryonic Development; Oogenesis; Obesity; Dyslipidemias
PubMed: 37400924
DOI: 10.1186/s40001-023-01174-8 -
Genes Sep 2023The yak () is a unique breed living on the Qinghai-Tibet Plateau and its surrounding areas, providing locals with a variety of vital means of living and production.... (Review)
Review
The yak () is a unique breed living on the Qinghai-Tibet Plateau and its surrounding areas, providing locals with a variety of vital means of living and production. However, the yak has poor sexual maturity and low fertility. High-quality mature oocytes are the basis of animal breeding technology. Recently, in vitro culturing of oocytes and embryo engineering technology have been applied to yak breeding. However, compared to those observed in vivo, the maturation rate and developmental capacity of in vitro oocytes are still low, which severely limits the application of in vitro fertilization and embryo production in yaks. This review summarizes the endogenous and exogenous factors affecting the in vitro maturation (IVM) and developmental ability of yak oocytes reported in recent years and provides a theoretical basis for obtaining high-quality oocytes for in vitro fertilization and embryo production in yaks.
Topics: Animals; Cattle; Blastocyst; Oocytes; Oogenesis; Fertilization in Vitro; Embryo, Mammalian
PubMed: 37895231
DOI: 10.3390/genes14101882 -
Reproductive Biology and Endocrinology... Oct 2023In human female primordial germ cells, the transition from mitosis to meiosis begins from the fetal stage. In germ cells, meiosis is arrested at the diplotene stage of... (Review)
Review
In human female primordial germ cells, the transition from mitosis to meiosis begins from the fetal stage. In germ cells, meiosis is arrested at the diplotene stage of prophase in meiosis I (MI) after synapsis and recombination of homologous chromosomes, which cannot be segregated. Within the follicle, the maintenance of oocyte meiotic arrest is primarily attributed to high cytoplasmic concentrations of cyclic adenosine monophosphate (cAMP). Depending on the specific species, oocytes can remain arrested for extended periods of time, ranging from months to even years. During estrus phase in animals or the menstrual cycle in humans, the resumption of meiosis occurs in certain oocytes due to a surge of luteinizing hormone (LH) levels. Any factor interfering with this process may lead to impaired oocyte maturation, which in turn affects female reproductive function. Nevertheless, the precise molecular mechanisms underlying this phenomenon has not been systematically summarized yet. To provide a comprehensive understanding of the recently uncovered regulatory network involved in oocyte development and maturation, the progress of the cellular and molecular mechanisms of oocyte nuclear maturation including meiosis arrest and meiosis resumption is summarized. Additionally, the advancements in understanding the molecular cytoplasmic events occurring in oocytes, such as maternal mRNA degradation, posttranslational regulation, and organelle distribution associated with the quality of oocyte maturation, are reviewed. Therefore, understanding the pathways regulating oocyte meiotic arrest and resumption will provide detailed insight into female reproductive system and provide a theoretical basis for further research and potential approaches for novel disease treatments.
Topics: Animals; Female; Humans; Oogenesis; Oocytes; Meiosis; Meiotic Prophase I; Ovarian Follicle
PubMed: 37784186
DOI: 10.1186/s12958-023-01143-0 -
Nature Communications Feb 2024Mitochondria are inherited exclusively from the mothers and are required for the proper development of embryos. Hence, germline mitochondrial quality is highly regulated...
Mitochondria are inherited exclusively from the mothers and are required for the proper development of embryos. Hence, germline mitochondrial quality is highly regulated during oogenesis to ensure oocyte viability. How nutrient availability influences germline mitochondrial quality control is unclear. Here we find that fasting leads to the accumulation of mitochondrial clumps and oogenesis arrest in Drosophila. Fasting induces the downregulation of the DIP1-Clueless pathway, leading to an increase in the expression of a stable intronic sequence RNA called sisR-1. Mechanistically, sisR-1 localizes to the mitochondrial clumps to inhibit the poly-ubiquitination of the outer mitochondrial protein Porin/VDAC1, thereby suppressing p62-mediated mitophagy. Alleviation of the fasting-induced high sisR-1 levels by either sisR-1 RNAi or refeeding leads to mitophagy, the resumption of oogenesis and an improvement in oocyte quality. Thus, our study provides a possible mechanism by which fasting can improve oocyte quality by modulating the mitochondrial quality control pathway. Of note, we uncover that the sisR-1 response also regulates mitochondrial clumping and oogenesis during protein deprivation, heat shock and aging, suggesting a broader role for this mechanism in germline mitochondrial quality control.
Topics: Animals; Introns; Mitochondria; Oocytes; Drosophila; Nutrients
PubMed: 38341415
DOI: 10.1038/s41467-024-45651-y -
Development (Cambridge, England) Oct 2023Lipid droplets (LDs), crucial regulators of lipid metabolism, accumulate during oocyte development. However, their roles in fertility remain largely unknown. During...
Lipid droplets (LDs), crucial regulators of lipid metabolism, accumulate during oocyte development. However, their roles in fertility remain largely unknown. During Drosophila oogenesis, LD accumulation coincides with the actin remodeling necessary for follicle development. Loss of the LD-associated Adipose Triglyceride Lipase (ATGL) disrupts both actin bundle formation and cortical actin integrity, an unusual phenotype also seen when the prostaglandin (PG) synthase Pxt is missing. Dominant genetic interactions and PG treatment of follicles indicate that ATGL acts upstream of Pxt to regulate actin remodeling. Our data suggest that ATGL releases arachidonic acid (AA) from LDs to serve as the substrate for PG synthesis. Lipidomic analysis detects AA-containing triglycerides in ovaries, and these are increased when ATGL is lost. High levels of exogenous AA block follicle development; this is enhanced by impairing LD formation and suppressed by reducing ATGL. Together, these data support the model that AA stored in LD triglycerides is released by ATGL to drive the production of PGs, which promote the actin remodeling necessary for follicle development. We speculate that this pathway is conserved across organisms to regulate oocyte development and promote fertility.
Topics: Animals; Prostaglandins; Lipid Droplets; Actins; Adipogenesis; Drosophila; Lipase; Peroxidases; Drosophila Proteins
PubMed: 37306387
DOI: 10.1242/dev.201516 -
PLoS Genetics Aug 2023Localization of oskar mRNA to the posterior of the Drosophila oocyte is essential for abdominal patterning and germline development. oskar localization is a multi-step...
Localization of oskar mRNA to the posterior of the Drosophila oocyte is essential for abdominal patterning and germline development. oskar localization is a multi-step process involving temporally and mechanistically distinct transport modes. Numerous cis-acting elements and trans-acting factors have been identified that mediate earlier motor-dependent transport steps leading to an initial accumulation of oskar at the posterior. Little is known, however, about the requirements for the later localization phase, which depends on cytoplasmic flows and results in the accumulation of large oskar ribonucleoprotein granules, called founder granules, by the end of oogenesis. Using super-resolution microscopy, we show that founder granules are agglomerates of smaller oskar transport particles. In contrast to the earlier kinesin-dependent oskar transport, late-phase localization depends on the sequence as well as on the structure of the spliced oskar localization element (SOLE), but not on the adjacent exon junction complex deposition. Late-phase localization also requires the oskar 3' untranslated region (3' UTR), which targets oskar to founder granules. Together, our results show that 3' UTR-mediated targeting together with SOLE-dependent agglomeration leads to accumulation of oskar in large founder granules at the posterior of the oocyte during late stages of oogenesis. In light of previous work showing that oskar transport particles are solid-like condensates, our findings indicate that founder granules form by a process distinct from that of well-characterized ribonucleoprotein granules like germ granules, P bodies, and stress granules. Additionally, they illustrate how an individual mRNA can be adapted to exploit different localization mechanisms depending on the cellular context.
Topics: Animals; 3' Untranslated Regions; Cytoplasm; Cytoplasmic Ribonucleoprotein Granules; Drosophila; RNA, Messenger; Stress Granules
PubMed: 37624861
DOI: 10.1371/journal.pgen.1010877 -
Biology Direct Oct 2023Bcl-B is a poorly understood protein of the Bcl-2 family that is highly expressed in many healthy tissues and tumor types. Bcl-B is considered an antiapoptotic protein,... (Review)
Review
Bcl-B is a poorly understood protein of the Bcl-2 family that is highly expressed in many healthy tissues and tumor types. Bcl-B is considered an antiapoptotic protein, but many reports have revealed its contradictory roles in different cancer types. In this mini-review, we elucidate the functions of Bcl-B in normal conditions and various pathologies, its regulation of programmed cell death, its oncogene/oncosuppressor activity in tumorigenesis, its impact on drug-acquired resistance, and possible approaches to inhibit Bcl-B.
Topics: Humans; Proto-Oncogene Proteins c-bcl-2; Apoptosis; Neoplasms
PubMed: 37899453
DOI: 10.1186/s13062-023-00431-4