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IScience May 2024Tissue development, homeostasis, and repair all require efficient progenitor expansion. Lysine-specific demethylase 1 (Lsd1) maintains plastic epigenetic states to...
Tissue development, homeostasis, and repair all require efficient progenitor expansion. Lysine-specific demethylase 1 (Lsd1) maintains plastic epigenetic states to promote progenitor proliferation while overexpressed Lsd1 protein causes oncogenic gene expression in cancer cells. However, the precise regulation of Lsd1 protein expression at the molecular level to drive progenitor differentiation remains unclear. Here, using oogenesis as our experimental system, we discovered molecular machineries that modify Lsd1 protein stability . Through genetic and biochemical analyses, an E3 ubiquitin ligase, Bre1, was identified as required for follicle progenitor differentiation, likely by mediating Lsd1 protein degradation. Interestingly, specific Lsd1-interacting long non-coding RNAs () were found to antagonize Bre1-mediated Lsd1 protein degradation. The intricate interplay discovered among the Lsd1 complex, and Bre1 provides insight into how Lsd1 protein stability is fine-tuned to underlie progenitor differentiation .
PubMed: 38655201
DOI: 10.1016/j.isci.2024.109683 -
Nutrition & Diabetes Apr 2024The number of patients with type 1 diabetes rises rapidly around the world in recent years. Maternal diabetes has a detrimental effect on reproductive outcomes due to...
BACKGROUND
The number of patients with type 1 diabetes rises rapidly around the world in recent years. Maternal diabetes has a detrimental effect on reproductive outcomes due to decreased oocyte quality. However, the strategies to improve the oocyte quality and artificial reproductive technology (ART) efficiency of infertile females suffering from diabetes have not been fully studied. In this study, we aimed to examine the effects of nicotinamide mononucleotide (NMN) on oocyte maturation of mouse with type 1 diabetes mouse and explore the underlying mechanisms of NMN's effect.
METHODS
Streptozotocin (STZ) was used to establish the mouse models with type 1 diabetes. The successful establishment of the models was confirmed by the results of body weight test, fasting blood glucose test and haematoxylin and eosin (H&E) staining. The in vitro maturation (IVM) rate of oocytes from diabetic mice was examined. Immunofluorescence staining (IF) was performed to examine the reactive oxygen species (ROS) level, spindle/chromosome structure, mitochondrial function, actin dynamics, DNA damage and histone modification of oocytes, which are potential factors affecting the oocyte quality. The quantitative reverse transcription PCR (RT-qPCR) was used to detect the mRNA levels of Sod1, Opa1, Mfn2, Drp1, Sirt1 and Sirt3 in oocytes.
RESULTS
The NMN supplementation increased the oocyte maturation rate of the mice with diabetes. Furthermore, NMN supplementation improved the oocyte quality by rescuing the actin dynamics, reversing meiotic defects, improving the mitochondrial function, reducing ROS level, suppressing DNA damage and restoring changes in histone modifications of oocytes collected from the mice with diabetes.
CONCLUSION
NMN could improve the maturation rate and quality of oocytes in STZ-induced diabetic mice, which provides a significant clue for the treatment of infertility of the patients with diabetes.
Topics: Animals; Mice; Female; Oocytes; Diabetes Mellitus, Type 1; Diabetes Mellitus, Experimental; Reactive Oxygen Species; Nicotinamide Mononucleotide; Mitochondria; Sirtuin 1; Sirtuin 3; In Vitro Oocyte Maturation Techniques; Superoxide Dismutase-1; DNA Damage; Streptozocin; Oogenesis; Dynamins
PubMed: 38653987
DOI: 10.1038/s41387-024-00280-8 -
BMC Medical Genomics Apr 2024Premature ovarian insuffiency (POI) is one of the main cause behind infertility. The genetic analysis of POI should be part of the clinical diagnostics, as several genes...
BACKGROUND
Premature ovarian insuffiency (POI) is one of the main cause behind infertility. The genetic analysis of POI should be part of the clinical diagnostics, as several genes have been implicated in the genetic background of it. The aim of our study was to analyse the genetic background of POI in a Hungarian cohort.
METHODS
The age of onset was between 15 and 39 years. All patients had the 46,XX karyotype and they were prescreened for the most frequent POI associated FMR1 premutation. To identify genetic alterations next-generation sequencing (NGS) of 31 genes which were previously associated to POI were carried out in 48 unrelated patients from Hungary.
RESULTS
Monogenic defect was identified in 16.7% (8 of 48) and a potential genetic risk factor was found in 29.2% (14 of 48) and susceptible oligogenic effect was described in 12.5% (6 of 48) of women with POI using the customized targeted panel sequencing. The genetic analysis identified 8 heterozygous damaging and 4 potentially damaging variants in POI-associated genes. Further 10 potential genetic risk factors were detected in seven genes, from which EIF2B and GALT were the most frequent. These variants were related to 15 genes: AIRE, ATM, DACH2, DAZL, EIF2B2, EIF2B4, FMR1, GALT, GDF9, HS6ST2, LHCGR, NOBOX, POLG, USP9X and XPNPEP2. In six cases, two or three coexisting damaging mutations and risk variants were identified.
CONCLUSIONS
POI is characterized by heterogenous phenotypic features with complex genetic background that contains increasing number of genes. Deleterious variants, which were detected in our cohort, related to gonadal development (oogenesis and folliculogenesis), meiosis and DNA repair, hormonal signaling, immune function, and metabolism which were previously associated with the POI phenotype. This is the first genetic epidemiology study targeting POI associated genes in Hungary. The frequency of variants in different POI associated genes were similar to the literature, except EIF2B and GALT. Both of these genes potential risk factor were detected which could influence the phenotype, although it is unlikely that they can be responsible for the development of the disease by themselves. Advances of sequencing technologies make it possible to aid diagnostics of POI Since individual patients show high phenotypic variance because of the complex network controlling human folliculogenesis. Comprehensive NGS screening by widening the scope to genes which were previously linked to infertility may facilitate more accurate, quicker and cheaper genetic diagnoses for POI. The investigation of patient's genotype could support clinical decision-making process and pave the way for future clinical trials and therapies.
Topics: Humans; Female; Primary Ovarian Insufficiency; High-Throughput Nucleotide Sequencing; Adult; Hungary; Adolescent; Young Adult; Genetic Testing; Genetic Predisposition to Disease; Mutation
PubMed: 38649916
DOI: 10.1186/s12920-024-01873-z -
Development (Cambridge, England) Oct 2024Ecdysone-induced protein 93 (E93), known as the 'adult-specifier' transcription factor in insects, triggers metamorphosis in both hemimetabolous and holometabolous...
Ecdysone-induced protein 93 (E93), known as the 'adult-specifier' transcription factor in insects, triggers metamorphosis in both hemimetabolous and holometabolous insects. Although E93 is conserved in ametabolous insects, its spatiotemporal expression and physiological function remain poorly understood. In this study, we first discover that, in the ametabolous firebrat Thermobia domestica, the previtellogenic ovary exhibits cyclically high E93 expression, and E93 mRNA is broadly distributed in previtellogenic ovarioles. E93 homozygous mutant females of T. domestica exhibit severe fecundity deficiency due to impaired previtellogenic development of the ovarian follicles, likely because E93 induces the expression of genes involved in ECM (extracellular matrix)-receptor interactions during previtellogenesis. Moreover, we reveal that in the hemimetabolous cockroach Blattella germanica, E93 similarly promotes previtellogenic ovarian development. In addition, E93 is also essential for vitellogenesis that is necessary to guarantee ovarian maturation and promotes the vitellogenesis-previtellogenesis switch in the fat body of adult female cockroaches. Our findings deepen the understanding of the roles of E93 in controlling reproduction in insects, and of E93 expression and functional evolution, which are proposed to have made crucial contributions to the origin of insect metamorphosis.
Topics: Animals; Female; Reproduction; Metamorphosis, Biological; Ovary; Gene Expression Regulation, Developmental; Vitellogenesis; Insect Proteins; Transcription Factors; Drosophila Proteins
PubMed: 38646855
DOI: 10.1242/dev.202518 -
Reproductive Biology Jun 2024Fibroblast growth factor 10 (FGF10) plays critical roles in oocyte maturation and embryonic development; however, the specific pathway by which FGF10 promotes in vitro...
Fibroblast growth factor 10 (FGF10) plays critical roles in oocyte maturation and embryonic development; however, the specific pathway by which FGF10 promotes in vitro maturation of buffalo oocytes remains elusive. The present study was aimed at investigating the mechanism underlying effects of the FGF10-mediated extracellular regulated protein kinases (ERK) pathway on oocyte maturation and embryonic development in vitro. MEK1/2 (mitogen-activated protein kinase kinase) inhibitor U0126, alone or in combination with FGF10, was added to the maturation culture medium during maturation of the cumulus oocyte complex. Morphological observations, orcein staining, apoptosis detection, and quantitative real-time PCR were performed to evaluate oocyte maturation, embryonic development, and gene expression. U0126 affected oocyte maturation and embryonic development in vitro by substantially reducing the nuclear maturation of oocytes and expansion of the cumulus while increasing the apoptosis of cumulus cells. However, it did not have a considerable effect on glucose metabolism. These findings suggest that blocking the MEK/ERK pathway is detrimental to the maturation and embryonic development potential of buffalo oocytes. Overall, FGF10 may regulate the nuclear maturation of oocytes and cumulus cell expansion and apoptosis but not glucose metabolism through the MEK/ERK pathway. Our findings indicate that FGF10 regulates resumption of meiosis and expansion and survival of cumulus cells via MEK/ERK signaling during in vitro maturation of buffalo cumulus oocyte complexes. Elucidation of the mechanism of action of FGF10 and insights into oocyte maturation should advance buffalo breeding. Further studies should examine whether enhancement of MEK/ERK signaling improves embryonic development in buffalo.
Topics: Animals; Buffaloes; Fibroblast Growth Factor 10; Butadienes; Oocytes; In Vitro Oocyte Maturation Techniques; Nitriles; Female; Oogenesis; Cumulus Cells; Apoptosis; MAP Kinase Signaling System; Embryonic Development; MAP Kinase Kinase 2
PubMed: 38643607
DOI: 10.1016/j.repbio.2024.100883 -
Communications Biology Apr 2024
PubMed: 38637608
DOI: 10.1038/s42003-024-06157-x -
Veterinary Research Communications Apr 2024Surfactant protein A (SP-A) and Surfactant protein D (SP-D) glycoproteins play a crucial role in maintaining lung homeostasis and lung host defense. Interestingly, these...
Surfactant protein A (SP-A) and Surfactant protein D (SP-D) glycoproteins play a crucial role in maintaining lung homeostasis and lung host defense. Interestingly, these proteins are also expressed in extra-pulmonary tissues, including the female genital tract. The ovarian tissue, where SP-A and SP-D expression increases with follicular development, may serve as the primary site of defense for this tissue. However, their functions in these tissues are not well understood and are currently an active area of research. Therefore, the objective of this study is to investigate the expression of SP-A and SP-D in the ovine ovary throughout the ovarian cycle using immunohistochemistry by semiquantitative intensity classification and Western blotting techniques. These findings revealed the presence of SP-A and SP-D in various compartments of the ovary, such as the follicular epithelium, granulosa cells, cumulus cells, theca cells, oocyte I, follicular fluid, and luteal cells of Graafian follicles, excluding the corpus albicans. SP-A and SP-D likely act as a first line of defense against potential pathogens that infiltrate the ovaries. Further investigation of the differential expression of SP-A and SP-D proteins in ovarian follicles will provide a basis for understanding their interactions with key proteins involved in oogenesis.
PubMed: 38635105
DOI: 10.1007/s11259-024-10367-3 -
Scientific Reports Apr 2024Honey bees are social insects, and each colony member has unique morphological and physiological traits associated with their social tasks. Previously, we identified a...
Honey bees are social insects, and each colony member has unique morphological and physiological traits associated with their social tasks. Previously, we identified a long non-coding RNA from honey bees, termed Nb-1, whose expression in the brain decreases associated with the age-polyethism of workers and is detected in some neurosecretory cells and octopaminergic neurons, suggesting its role in the regulation of worker labor transition. Herein, we investigated its spatially and temporary-regulated/sex-specific expression. Nb-1 was expressed as an abundant maternal RNA during oogenesis and embryogenesis in both sexes. In addition, Nb-1 was expressed preferentially in the proliferating neuroblasts of the mushroom bodies (a higher-order center of the insect brain) in the pupal brains, suggesting its role in embryogenesis and mushroom body development. On the contrary, Nb-1 was expressed in a drone-specific manner in the pupal and adult retina, suggesting its role in the drone visual development and/or sense. Subcellular localization of Nb-1 in the brain during development differed depending on the cell type. Considering that Nb-1 is conserved only in Apidae, our findings suggest that Nb-1 potentially has pleiotropic functions in the expression of multiple developmental, behavioral, and physiological traits, which are closely associated with the honey bee lifecycle.
Topics: Female; Male; Bees; Animals; RNA, Long Noncoding; Niobium; Brain; Neurons; Head; Pupa
PubMed: 38622193
DOI: 10.1038/s41598-024-59494-6 -
BioRxiv : the Preprint Server For... Apr 2024Quantitative live imaging is a valuable tool that offers insights into cellular dynamics. However, many fundamental biological processes are incompatible with current...
Quantitative live imaging is a valuable tool that offers insights into cellular dynamics. However, many fundamental biological processes are incompatible with current live imaging modalities. oogenesis is a well-studied system that has provided molecular insights into a range of cellular and developmental processes. The length of the oogenesis coupled with the requirement for inputs from multiple tissues has made long-term culture challenging. Here, we have developed Bellymount-Pulsed Tracking (Bellymount-PT), which allows continuous, non-invasive live imaging of oogenesis inside the female abdomen for up to 16 hours. Bellymount-PT improves upon the existing Bellymount technique by adding pulsed anesthesia with periods of feeding that support the long-term survival of flies during imaging. Using Bellymount-PT we measure key events of oogenesis including egg chamber growth, yolk uptake, and transfer of specific proteins to the oocyte during nurse cell dumping with high spatiotemporal precision within the abdomen of a live female.
PubMed: 38617254
DOI: 10.1101/2024.03.31.587498 -
Science Advances Apr 2024During Drosophila oogenesis, the Oskar (OSK) RNA binding protein (RBP) determines the amount of germ plasm that assembles at the posterior pole of the oocyte. Here, we...
During Drosophila oogenesis, the Oskar (OSK) RNA binding protein (RBP) determines the amount of germ plasm that assembles at the posterior pole of the oocyte. Here, we identify mechanisms that subsequently regulate germ plasm assembly in the early embryo. We show that the Smaug (SMG) RBP is transported into the germ plasm of the early embryo where it accumulates in the germ granules. SMG binds to and represses translation of the messenger RNA (mRNA) as well as the () mRNA, which encodes an RBP that we show promotes germ plasm production. Loss of SMG or mutation of SMG's binding sites in the or mRNA results in excess translation of these transcripts in the germ plasm, accumulation of excess germ plasm, and budding of excess primordial germ cells (PGCs). Therefore, SMG triggers a posttranscriptional regulatory pathway that attenuates the amount of germ plasm in embryos to modulate the number of PGCs.
Topics: Animals; Drosophila; Cytoplasm; Germ Cells; Lizards; RNA, Messenger; Cell Count
PubMed: 38608012
DOI: 10.1126/sciadv.adg7894