ZAR1/2-Regulated Epigenetic Modifications are Essential for Age-Associated Oocyte Quality Maintenance and Zygotic Activation.

The developmental competence and epigenetic progression of oocytes gradually become dysregulated with increasing maternal age. However, the mechanisms underlying age-related epigenetic regulation in oocytes remain poorly understood. Zygote arrest proteins 1 and 2 (ZAR1/2) are two maternal factors with partially redundant roles in maintaining oocyte quality, mainly known by regulating mRNA stability.

PCBP1/2 and TDP43 Function as NAT10 Adaptors to Mediate mRNA acC Formation in Mammalian Cells.

Massive numbers of modified bases in mRNAs sculpt the epitranscriptome and play vital roles in RNA metabolism. The only known acetylated RNA modification, N-4-acetylcytidine (acC), is highly conserved across cell types and among species. Although the GCN5-related acetyltransferase 10 (NAT10) functions as an acC writer, the mechanism underlying the acetylation process is largely unknown.

Distinct Olfactory Bulb-Cortex Neural Circuits Coordinate Cognitive Function in Parkinson's Disease.

Cognitive dysfunction stands as a prevalent and consequential non-motor manifestation in Parkinson's disease (PD). Although dysfunction of the olfactory system has been recognized as an important predictor of cognitive decline, the exact mechanism by which aberrant olfactory circuits contribute to cognitive dysfunction in PD is unclear. Here, we provide the first evidence for abnormal functional connectivity across olfactory bulb (OB) and piriform cortex (PC) or entorhinal cortex (EC) by clinical fMRI, and dysfunction of neural coherence in the olfactory system in PD mice.

DCAF2 regulates the proliferation and differentiation of mouse progenitor spermatogonia by targeting p21 and thymine DNA glycosylase.

DDB1-Cullin-4-associated factor-2 (DCAF2, also known as DTL or CDT2), a conserved substrate recognition protein of Cullin-RING E3 ligase 4 (CRL4), recognizes and degrades several substrate proteins during the S phase to maintain cell cycle progression and genome stability. Dcaf2 mainly expressed in germ cells of human and mouse. Our study found that Dcaf2 was expressed in mouse spermatogonia and spermatocyte.

CRL4 E3 ubiquitin ligase targets MeCP2 for degradation to prevent DNA hypermethylation and ensure normal transcription in growing oocytes.

The DNA methylation is gradually acquired during oogenesis, a process sustained by successful follicle development. However, the functional roles of methyl-CpG-binding protein 2 (MeCP2), an epigenetic regulator displaying specifical binding with methylated DNA, remains unknown in oogenesis. In this study, we found MeCP2 protein was highly expressed in primordial and primary follicle, but was almost undetectable in secondary follicles.

Zygotic Splicing Activation of the Transcriptome is a Crucial Aspect of Maternal-to-Zygotic Transition and Required for the Conversion from Totipotency to Pluripotency.

During maternal-to-zygotic transition (MZT) in the embryo, mRNA undergoes complex post-transcriptional regulatory processes. However, it is unclear whether and how alternative splicing plays a functional role in MZT. By analyzing transcriptome changes in mouse and human early embryos, dynamic changes in alternative splicing during MZT are observed and a previously unnoticed process of zygotic splicing activation (ZSA) following embryonic transcriptional activation is described.

Biallelic variants in () cause female infertility characterized by oocyte maturation arrest.

Human oocyte maturation arrest represents one of the severe conditions for female patients with primary infertility. However, the genetic factors underlying this human disease remain largely unknown. The spindle assembly checkpoint (SAC) is an intricate surveillance mechanism that ensures accurate segregation of chromosomes throughout cell cycles.

A long-acting recombinant FSH supports high-quality mouse follicle development and oocyte maturation in vitro by coordinating somatic and germ cell transcriptomes.

Strategies to maximize individual fertility chances are constant requirements of ART. In vitro folliculogenesis may represent a valid option to create a large source of immature ovarian follicles in ART. Efforts are being made to set up mammalian follicle culture protocols with suitable FSH stimuli.

Divergent projections of the prelimbic cortex mediate autism- and anxiety-like behaviors.

The comorbidity of autism spectrum disorder and anxiety is common, but the underlying circuitry is poorly understood. Here, Tmem74 mice showed autism- and anxiety-like behaviors along with increased excitability of pyramidal neurons (PNs) in the prelimbic cortex (PL), which were reversed by Tmem74 re-expression and chemogenetic inhibition in PNs of the PL. To determine the underlying circuitry, we performed conditional deletion of Tmem74 in the PNs of PL of mice, and we found that alterations in the PL projections to fast-spiking interneurons (FSIs) in the dorsal striatum (dSTR) (PL-dSTR) mediated the hyperexcitability of FSIs and autism-like behaviors and that alterations in the PL projections to the PNs of the basolateral amygdaloid nucleus (BLA) (PL-BLA) mediated the hyperexcitability of PNs and anxiety-like behaviors.

Translation regulatory factor BZW1 regulates preimplantation embryo development and compaction by restricting global non-AUG Initiation.

Protein synthesis is an essential step in gene expression during the development of mammalian preimplantation embryos. This is a complex and highly regulated process. The accuracy of the translation initiation codon is important in various gene expression programs.

PABPN1 functions as a hub in the assembly of nuclear poly(A) domains that are essential for mouse oocyte development.

Growing oocytes store a large amount of maternal mRNA to support the subsequent "maternal-zygotic transition" process. At present, it is not clear how the growing oocytes store and process the newly transcribed mRNA under physiological conditions. In this study, we report non-membrane-bound compartments, nuclear poly(A) domains (NPADs), as the hub for newly transcribed mRNA, in developing mouse oocytes.

The RNA ligase RNA terminal phosphate cyclase B regulates mRNA alternative splicing and is required for mouse oocyte development and maintenance.

Recent large-scale mRNA sequencing has shown that introns are retained in 5-10% of mRNA, and these events are named intron retention (IR). IR has been recognized as a key mechanism in the regulation of gene expression. However, the role of this mechanism in female reproduction in mammals remains unclear.

NAT10-mediated N4-acetylcytidine modification is required for meiosis entry and progression in male germ cells.

Post-transcriptional RNA modifications critically regulate various biological processes. N4-acetylcytidine (ac4C) is an epi-transcriptome, which is highly conserved in all species. However, the in vivo physiological functions and regulatory mechanisms of ac4C remain poorly understood, particularly in mammals.

Ultrasensitive Ribo-seq reveals translational landscapes during mammalian oocyte-to-embryo transition and pre-implantation development.

In mammals, translational control plays critical roles during oocyte-to-embryo transition (OET) when transcription ceases. However, the underlying regulatory mechanisms remain challenging to study. Here, using low-input Ribo-seq (Ribo-lite), we investigated translational landscapes during OET using 30-150 mouse oocytes or embryos per stage.

Dynamic mRNA degradome analyses indicate a role of histone H3K4 trimethylation in association with meiosis-coupled mRNA decay in oocyte aging.

A decrease in oocyte developmental potential is a major obstacle for successful pregnancy in women of advanced age. However, the age-related epigenetic modifications associated with dynamic transcriptome changes, particularly meiotic maturation-coupled mRNA clearance, have not been adequately characterized in human oocytes. This study demonstrates a decreased storage of transcripts encoding key factors regulating the maternal mRNA degradome in fully grown oocytes of women of advanced age.

Biallelic variants in MOS cause large polar body in oocyte and human female infertility.

Study Question: What is the genetic basis of female infertility involving abnormal oocyte morphology with the production of a large first polar body (PB1)?

Summary Answer: The homozygous missense variant (c.791C>G) and compound missense variants (c.596A>T and c.

USP16-mediated histone H2A lysine-119 deubiquitination during oocyte maturation is a prerequisite for zygotic genome activation.

Maternal-to-zygotic transition (MZT) is the first and key step in the control of animal development and intimately related to changes in chromatin structure and histone modifications. H2AK119ub1, an important epigenetic modification in regulating chromatin configuration and function, is primarily catalyzed by PRC1 and contributes to resistance to transcriptional reprogramming in mouse embryos. In this study, the genome-wide dynamic distribution of H2AK119ub1 during MZT in mice was investigated using chromosome immunoprecipitation and sequencing.

Five questions toward mRNA degradation in oocytes and preimplantation embryos: when, who, to whom, how, and why?†.

RNA-the primary product of the genome-is subject to various biological events during its lifetime. During mammalian gametogenesis and early embryogenesis, germ cells and preimplantation embryos undergo marked changes in the transcriptome, including mRNA turnover. Various factors, including specialized proteins, RNAs, and organelles, function in an intricate degradation system, and the degradation selectivity is determined by effectors and their target mRNAs.

Revisiting ZAR proteins: the understudied regulator of female fertility and beyond.

Putative RNA-binding proteins (RBPs), zygote arrested-1 (ZAR1), and ZAR2 (also known as ZAR1L), have been identified as maternal factors that mainly function in oogenesis and embryogenesis. Despite divergence in their spatio-temporal expression among species, the CxxC structure of the C-terminus of ZAR proteins is highly conserved and is reported to be the functional domain for the activity of the RBPs of ZAR proteins. In oocytes from Xenopus laevis and zebrafish, ZAR proteins have been reported to bind to maternal transcripts and inhibit translation in immature growing oocytes, whereas in fully grown mouse oocytes, they promote the translation during meiotic maturation.