An overview of different methods to establish a murine premature ovarian failure model DOI Creative Commons

Negar Pouladvand,

Mahnaz Azarnia, Hadis Zeinali

et al.

Animal Models and Experimental Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Abstract Premature ovarian failure (POF)is defined as the loss of normal function before age 40 and is characterized by increased gonadotropin levels decreased estradiol reserve, often leading to infertility. The incomplete understanding pathogenesis POF a major impediment development effective treatments for this disease, so use animal models promising option investigating identifying molecular mechanisms involved in patients developing therapeutic agents. As mice rats are most commonly used research, review article considers studies that murine models. In based on recent studies, first, we introduce 10 different methods inducing models, then demonstrate advantages disadvantages each one, finally, suggest practical method model these animals. This may help researchers find creating appropriate their type study suits purpose research.

Language: Английский

Heterozygous Eif4nif1 Stop Gain Mice Replicate the Primary Ovarian Insufficiency Phenotype in Women DOI Creative Commons
Mika Moriwaki, Lihua Liu, Emma James

et al.

Endocrinology, Journal Year: 2025, Volume and Issue: 166(3)

Published: Jan. 17, 2025

We created the c.1286C>G stop-gain mutation found in a family with primary ovarian insufficiency (POI) at age 30 years. The Eif4enif1 C57/Bl6 transgenic mouse model contained floxed exon 10-19 cassette conditional knock-in containing 10. hybrid offspring of CMV-Cre mice Eif4enif1WT/flx were designated Eif4enif1WT/Δ for simplicity. A subset female heterozygotes (Eif4enif1WT/Δ) had no litters. In those litters, final litter was earlier (5.4 ± 2.6 vs 10.5 0.7 months; P = .02). Heterozygous breeding pair (Eif4enif1WT/Δ × Eif4enif1WT/Δ) size 60% WT (3.9 2.0 6.5 3.0 pups/litter; < .001). genotypes 35% and 65% Eif4enif1WT/Δ, homozygotes. Homozygote embryos did not develop beyond 4- to 8-cell stage. number follicles ovaries from lower starting primordial (499 290 1445 381) follicle stage (1069 346 1450 193) on day 10 (P .05). preantral 21 (213 86 522 227; .01). Examination ribosome protected mRNAs demonstrated altered mRNA expression. replicate POI phenotype women based an end reproduction due oocyte loss. unique provides platform study regulation protein translation across embryo development mammals.

Language: Английский

Citations

1
Efficacy of Shuangdan Yangxue capsule combined with estradiol valerate and dydrogesterone in early-onset ovarian insufficiency DOI Creative Commons

Li Zhang,

Yue Sun, Chen Chen

et al.

Asian Journal of Surgery, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

Citations

0
Oocyte‐specific deletion of eukaryotic translation initiation factor 5 causes apoptosis of mouse oocytes within the early‐growing follicles by mitochondrial fission defect‐reactive oxygen species‐DNA damage DOI Creative Commons
Weiyong Wang, Huiyu Liu, Shuang Liu

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(8)

Published: Aug. 1, 2024

Abstract Background Mutations in several translation initiation factors are closely associated with premature ovarian insufficiency (POI), but the underlying pathogenesis remains largely unknown. Methods and results We generated eukaryotic factor 5 ( Eif5 ) conditional knockout mice aiming to investigate function of eIF5 during oocyte growth follicle development. Here, we demonstrated that deletion mouse primordial growing oocytes both resulted apoptosis within early‐growing follicles. Further studies revealed downregulated levels mitochondrial fission‐related proteins (p‐DRP1, FIS1, MFF MTFR) upregulated integrated stress response‐related (AARS1, SHMT2 SLC7A1) genes Atf4 , Ddit3 Fgf21 ). Consistent this, dysfunction characterized by elongated form, aggregated distribution beneath membrane, decreased adenosine triphosphate content mtDNA copy numbers, excessive accumulation reactive oxygen species (ROS) superoxide. Meanwhile, led a significant increase DNA damage response (γH2AX, p‐CHK2 p‐p53) proapoptotic (PUMA BAX), as well decrease anti‐apoptotic protein BCL‐xL. Conclusion These findings indicate follicles via fission defects, ROS damage. This study provides new insights into pathogenesis, genetic diagnosis potential therapeutic targets for POI. Key points leads arrest impairs proteins, followed dysfunction. Depletion causes pathway.

Language: Английский

Citations

2
Two mechanisms repress cyclin B1 translation to maintain prophase arrest in mouse oocytes DOI Creative Commons
Shiya Cheng, Melina Schuh

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 20, 2024

Abstract In mammals, oocytes are arrested in prophase of meiosis I for long periods time. Prophase arrest is critical reproduction because it allows to grow their full size support meiotic maturation and embryonic development. requires the inhibitory phosphorylation mitotic kinase CDK1. Whether also regulated at translational level unknown. Here, we show that by control dormant cyclin B1 mRNAs. Using Trim-Away, identify two mechanisms maintain dormancy thus arrest. First, a complex RNA-binding proteins DDX6, LSM14B CPEB1 directly represses translation through interacting with its 3’UTR. Second, cytoplasmic poly(A)-binding (PABPCs) indirectly repress other poly(A)-tail-less or short-tailed mRNAs sequestering machinery on long-tailed Together, demonstrate how coordinately regulate arrest, reveal an unexpected role PABPCs controlling mRNA dormancy.

Language: Английский

Citations

2
TP63 truncating mutation causes increased cell apoptosis and premature ovarian insufficiency by enhanced transcriptional activation of CLCA2 DOI Creative Commons

Yali Fan,

Shuya Chen,

Chunfang Chu

et al.

Journal of Ovarian Research, Journal Year: 2024, Volume and Issue: 17(1)

Published: March 25, 2024

Abstract Background Premature ovarian insufficiency (POI) is a severe disorder leading to female infertility. Genetic mutations are important factors causing POI. TP63-truncating mutation has been reported cause POI by increasing germ cell apoptosis, however what mediate this apoptosis remains unclear. Methods Ninety-three patients with were recruited from Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Whole-exome sequencing (WES) was performed for each patient. Sanger used confirm potential causative genetic variants. A minigene assay determine splicing effects of TP63 -truncating plasmid constructed. Real-time quantitative PCR, western blot analyses, dual luciferase reporter assays, immunofluorescence staining, assays study the underlying mechanism Results By WES 93 sporadic POI, we found 14-bp deletion covering splice site in gene. demonstrated that variant led exon 13 skipping during mRNA splicing, resulting generation truncated protein (TP63-mut). Overexpression TP63-mut accelerated apoptosis. Mechanistically, could bind promoter region CLCA2 activate transcription several times compared wild-type protein. Silencing using specific small interfering RNA (siRNA) or inhibiting Ataxia Telangiectasia Mutated (ATM) pathway KU55933 inhibitor attenuated caused expression. Conclusion Our findings revealed crucial role mediating pathogenesis, suggested therapeutic target

Language: Английский

Citations

2
POI-associated EIF4ENIF1 mutations exhibit impaired translation regulation abilities DOI
Yuxi Ding, Shuya Chen, Jing Jin

et al.

Gene, Journal Year: 2024, Volume and Issue: 917, P. 148456 - 148456

Published: April 9, 2024

Language: Английский

Citations

1
Premeiotic deletion of Eif2s2 causes oocyte arrest at the early diplotene stage and apoptosis in mice DOI Creative Commons
Wenjun Zhou, Biao Li,

Zhijuan Wang

et al.

Cell Proliferation, Journal Year: 2024, Volume and Issue: 57(12)

Published: July 24, 2024

Eukaryotic translation initiation factor 2 subunit (EIF2S2), a of the heterotrimeric G protein EIF2, is involved in translation. Our findings demonstrate that depletion Eif2s2 premeiotic germ cells causes oocyte arrest at pachytene and early diplotene stages 1 day postpartum (dpp) 5 dpp, respectively, eventually leads to apoptosis failure primordial follicle formation. Further studies reveal deletion downregulates homologous recombination-related mitochondrial fission-related levels, upregulates integrated stress response-related proteins mRNA levels. Consistently, significantly decreases expression dictyate genes compromises function, characterized by elongated shapes, decreased ATP levels mtDNA copy number, along with an excessive accumulation reactive oxygen species (ROS) superoxide. Furthermore, DNA damage response proapoptotic increase, while anti-apoptotic decrease Eif2s2-deleted mice. An increase oocytes positive cleaved-Caspase-3 TUNEL signals, alongside reduced Lamin B1 intensity, further indicates apoptosis. Collectively, meiotic stage impairing recombination, mainly through downregulation proteins, ROS subsequent damage.

Language: Английский

Citations

1
An overview of different methods to establish a murine premature ovarian failure model DOI Creative Commons

Negar Pouladvand,

Mahnaz Azarnia, Hadis Zeinali

et al.

Animal Models and Experimental Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Abstract Premature ovarian failure (POF)is defined as the loss of normal function before age 40 and is characterized by increased gonadotropin levels decreased estradiol reserve, often leading to infertility. The incomplete understanding pathogenesis POF a major impediment development effective treatments for this disease, so use animal models promising option investigating identifying molecular mechanisms involved in patients developing therapeutic agents. As mice rats are most commonly used research, review article considers studies that murine models. In based on recent studies, first, we introduce 10 different methods inducing models, then demonstrate advantages disadvantages each one, finally, suggest practical method model these animals. This may help researchers find creating appropriate their type study suits purpose research.

Language: Английский

Citations

0