Search Results (611)

WEE2, an oocyte-specific kinase of the WEE family, is a core regulator of oocyte meiosis. It maintains germinal vesicle (GV) arrest and prevents premature meiotic resumption by phosphorylating cyclin-dependent kinase 1 (CDK1), thereby inhibiting maturation-promoting factor (MPF) activity. WEE2 also regulates exit from metaphase II (MII), ensuring orderly meiotic progression. Consequently, the functional integrity of WEE2 is essential for female reproduction. Homozygous or compound heterozygous mutations in the WEE2 gene represent a major genetic cause of total fertilization failure and primary infertility, as these mutations lead to reduced or abolished kinase activity, impair meiotic control, and disrupt oocyte maturation and embryonic development. This review systematically summarizes the protein structure, core functions, and mutation types of WEE2, along with its association with total fertilization failure and female primary infertility. It also highlights research advances in WEE2-targeted inhibitors and discusses the potential applications and future directions of WEE2 in the diagnosis and management of reproductive disorders. Full article

Metformin (MET) plays crucial regulatory roles in mammalian oocyte meiosis, yet the concentration-dependent biphasic impacts of MET on porcine oocyte in vitro maturation (IVM) and the related molecular mechanisms remain poorly clarified. This study aimed to explore the distinct effects and underlying pathways of low- and high-dose MET in porcine oocytes. Different concentrations of MET (0, 7.5, 15, 30, 150, and 300 μM) were supplemented during oocyte IVM, with phenotypic detection, untargeted metabolomic analysis, and Nrf2 inhibitor (ML385) intervention performed for mechanism exploration. Results showed that 15 μM low-dose MET facilitated oocyte maturation, mitochondrial function and redox balance, while 300 μM high-dose MET caused obvious developmental damage. Mechanistically, low-dose MET triggered noncanonical AMPK activation independent of the AMP/ATP ratio and enhanced AMPK–Nrf2 antioxidant signaling, whereas high-dose MET induced energy stress and oxidative injury via inhibiting mitochondrial complex I. Blockade of Nrf2 further abolished the protective effects of low-dose MET. Collectively, this finding illustrates the biphasic actions of MET on porcine oocytes and provides a theoretical reference for optimizing porcine in vitro embryo production. Full article

This study identified the fertility alteration characteristics and cytological mechanisms of the thermo-photo-sensitive genic male sterile (TPSGMS) wheat line K64S. The fertility-sensitive stage of K64S extends from pollen mother cell formation to the tetrad development stage, with critical fertility alteration thresholds of 14–14.5 °C for temperature and 9–9.5 h for daylength. Under low-temperature and short-day conditions, K64S exhibits complete male sterility, whereas it returns to fertility under high-temperature and long-day conditions. Cytological analysis shows that K64S undergoes normal meiosis and successfully forms normal uninucleate microspores. 4′,6-diamidino-2-phenylindole (DAPI) staining revealed the uninucleate microspores failed to form binucleate microspores, with abortion occurring during the late uninucleate stage. Transmission electron microscopy indicates the pollen abortion in sterile K64S arises primarily from premature tapetal degeneration (a form of programmed cell death, PCD), initiated at the pollen mother cell stage, which disrupts nutrient supply and leads to abnormal nuclear division during subsequent microspore development. These findings provide insights into the cytological mechanism of pollen abortion in TPSGMS wheat and may guide hybrid wheat breeding and application. Full article

The northern pike (Esox lucius) is an economically important cold-water fish species in northern China. It exhibits pronounced sexual dimorphism, yet the molecular mechanism underlying its sex differentiation remains unclear, which hinders the development of aquaculture. Whole-transcriptome sequencing is a powerful approach for screening sex-related genes; however, no such study has been reported for this species to date. In this study, gonadal tissues from three female and three male E. lucius were collected for whole-transcriptome sequencing. A total of 14,941 differentially expressed messengerRNAs, 119 differentially expressed microRNAs, 229 differentially expressed circularRNAs, and 2055 differentially expressed long non-codingRNAs were identified. Functional enrichment analysis revealed that the differentially expressed genes were significantly enriched in pathways closely associated with sex differentiation, such as steroid hormone biosynthesis and oocyte meiosis. Several key sex-biased genes were identified, including female-biased genes (FANCL, DDX5, SRSF5B) and male-biased genes (STAR, FDX1B, ITGA2B). Furthermore, a competing endogenous RNA (ceRNA) regulatory network involving dre-miR-107b was constructed, which may represent a candidate for further investigation into sex differentiation in E. lucius. This study provides the first comprehensive whole-transcriptome dataset of female and male gonads in E. lucius, identifies key sex-biased genes and core pathways involved in its sex differentiation, and thereby identifies the dre-miR-107b-centered ceRNA network and key sex-biased genes (FANCL, DDX5, SRSF5B, STAR, FDX1B, ITGA2B) as core molecular players in sex differentiation of this species. Full article

Oocyte maturation is a pivotal event in teleost reproduction that directly determines egg quality, fertilization success, and the developmental competence of early embryos. However, the transcriptional and post-transcriptional regulatory mechanisms operating within oocytes during maturation in marine teleosts remain poorly understood. In the present study, the orange-spotted grouper (Epinephelus coioides), an economically important marine aquaculture species, was used as a model. Oocytes at four distinct maturation stages were obtained by microscopically removing the surrounding follicular layers, followed by integrated mRNA-seq and miRNA-seq analyses to characterize the molecular regulatory landscape underlying oocyte maturation and hydration. The results showed that, as maturation progressed, oocyte diameter and wet weight increased significantly, accompanied by a marked decrease in Na⁺ content, a significant increase in K⁺ content, and the continuous accumulation of most free amino acids, indicating the gradual establishment of an osmotic basis favorable for oocyte hydration. Transcriptomic analysis further revealed extensive transcriptional remodeling during both the early and late phases of maturation. Differentially expressed genes were significantly enriched in pathways related to oocyte meiosis, cytokine signaling, lipid metabolism, DNA replication, cell cycle regulation, ribosome biogenesis, spliceosome function, oxidative phosphorylation, and mitochondrial activity, suggesting that oocyte maturation is a dynamic process characterized by a shift from basal growth maintenance to metabolic reprogramming, maternal transcript remodeling, and terminal maturation responses. miRNA profiling identified a large number of stage-specific differentially expressed miRNAs, including let-7d-5p, miR-22a-3p, and novel-miR-20/27/118, whose predicted target genes were mainly enriched in ribosome-related pathways, oxidative phosphorylation, DNA replication, transcriptional regulation, and signal transduction. Moreover, the miRNA–TF–mRNA regulatory network demonstrated that miRNAs may not only directly repress target genes, but also mediate hierarchical regulatory cascades through transcription factors, thereby coordinately participating in cell cycle progression, cytoskeletal remodeling, vesicular transport, and immune- and cell communication-related responses. Collectively, this study provides the first systematic temporal atlas of mRNA and miRNA regulation during oocyte maturation and hydration at the oocyte level in a marine teleost, thereby deepening our understanding of the molecular basis of meiotic resumption and egg quality formation, and offering valuable theoretical support for the optimization of artificial breeding and the identification of key molecular targets in grouper reproduction. Full article

Polyploidization is a key pathway for species formation and genetic innovation; approximately 70% of angiosperms have undergone at least one whole-genome duplication event during their evolutionary history. To determine the genetic and phenotypic stability of artificially induced autotetraploids across generations, this study utilized a colchicine-induced autotetraploid of Gossypium herbaceum as experimental material and conducted systematic comparative analyses of morphological, cytological, and molecular marker characteristics in the S3 and S4 generations. The results showed that, compared with the 2×, seed weight in the S3 generation increased by 59.4% (to 89.22 mg), and in the S4 generation increased by 65.0% (to 92.40 mg), while there was no significant difference in fiber length. The leaf area of tetraploids decreased significantly during the flower-bell stage. Observation of pollen mother cell meiosis revealed that the proportions of normal tetrads in the S3 and S4 generations were 73.80% and 81.80%, respectively, and the proportions of normal pollen grains were 79.60% and 80.60%, respectively. Cytological stability was markedly improved in the S4 generation. A total of 34 alleles were amplified by SSR molecular marker analysis, of which 23 (67.60%) were polymorphic. The primers NBRI_G1015 and NAU1164 exhibited the highest polymorphism rates, at 87.50% and 83.30%, respectively. The average genetic diversity index (He) was 0.1411, indicating a highly inbred genetic background. The banding patterns of S3 and S4 are highly consistent, with strong signal intensity; not only do they amplify bands consistent with those of diploids, but they also exhibit specific new bands and band deletions. In summary, this autotetraploid material exhibits stable morphological advantages and genetic uniformity. As generations progress, its meiotic behavior and genetic structure tend to stabilize. The S4 generation exhibits greater cytological stability and genetic uniformity than the S3 generation, making it a highly promising new germplasm resource for cotton polyploid breeding. Full article

Seed initiation in Arabidopsis depends on regulatory transitions that begin before fertilization, yet these events are often treated as separate developmental episodes rather than as a connected sequence. Here, we synthesize evidence from megaspore mother cell (MMC) specification to endosperm cellularization and ask whether particular stage boundaries meet a narrow definition of developmental handover: a shift between dominant control logics, with detectable first-order consequences in the ensuing interval and acknowledged overlap across the boundary. This framework goes beyond canonical staging by distinguishing chronological succession from shifts in regulatory control, thereby clarifying where earlier states are expected to constrain later outcomes, which developmental boundaries are mechanistically well supported, and where further mechanistic resolution is most needed. We first examine how MMC singleness (restriction to a single reproductive founder cell per ovule primordium) emerges through coupled sporophytic restriction and local competence. We then consider how meiosis and female gametophyte maturation establish regulatory poise (an actively restrained and asymmetric mature female-gametophytic state), including cell-cycle restraint, companion-cell-restricted demethylation, and unequal gametic chromatin states that condition subsequent embryo and endosperm behavior. After fertilization, release of central-cell restraint, activation of an endosperm auxin program, and recruitment of maternal tissues together mark the onset of seed initiation. In this view, syncytial endosperm is an actively maintained developmental state shaped by parental dosage, epigenetic control, hormone signaling, and maternal interaction, whereas endosperm cellularization represents a regulated switch with seed-wide consequences. In Arabidopsis, the clearest handover is the mature female gametophyte-to-fertilization boundary, whereas the boundaries linking MMC specification to female gametophyte maturation and syncytial endosperm to cellularization remain provisional. Full article

In Saccharomyces cerevisiae (S. cerevisiae), sister kinetochores are mono-oriented during meiosis I to ensure accurate homolog segregation, a process dependent on Hrr25 kinase activity. However, its direct interactors remain poorly defined. To address this, we performed a yeast two-hybrid (Y2H) screen using Hrr25 as bait. HRR25 was cloned into a Y2H vector and functionally validated by complementation of a temperature-sensitive hrr25-ts mutant. Screening across three reading frames identified three putative interactors: Hed1, Cyr1, and Rep1. Additional open reading frames (ORFs), including DAD1, SYS1, and YDR015C were identified but were oppositely oriented to the GAL4 activation domain. Structural modeling and phosphorylation prediction identified high-confidence Hrr25 target residues, including S70/T73 on Hed1, S323 on Rep1, and S198/S527 on Cyr1, whereas Sys1 and YDR015C lacked favorable sites. Although Dad1 was not validated as a direct interactor from Y2H, S63 was identified as a favorable phosphorylation site, and its full-length ORF in the interacting clone and known biological role supported its inclusion. Among the meiotic candidates, Hed1 may link Hrr25 activity to homologous recombination, while Dad1 represents a plausible target for regulating kinetochore–microtubule interactions. Collectively, these findings identify new candidate interactors and substrates of Hrr25 and suggest a broader role in coordinating recombination and kinetochore function during meiosis, warranting further experimental validation. Full article

Systemic lupus erythematosus is an autoimmune disease that mainly affects women of reproductive age. Its pathological manifestations directly and indirectly negatively affect the ovarian reserve, the quality of oocytes, and the precise mechanisms of meiosis. This review presents the molecular mechanisms by which lupus damages ovarian tissue and meiosis in oocytes. The role of chronic inflammation, impaired hormonal levels, and the presence of specific autoantibodies are considered. The available data on how oocyte structures (meiotic spindle, actin cytoskeleton, membrane organelles and chromatin) are damaged by lupus symptoms are summarized. Full article

Background/Objective: RNA modifications, including N⁶-methyladenosine (m⁶A), 5-methylcytosine (m⁵C), 7-methylguanosine (m⁷G), N¹-methyladenosine (m¹A), pseudouridine (Ψ), N⁴-acetylcytidine (ac⁴C), 5-methoxycarbonylmethyl-2-thiouridine (mcm⁵s²U) and adenosine-to-inosine (A-to-I) editing, constitute a critical layer of post-transcriptional regulation that influences RNA stability, splicing, translation and degradation. This review aims to systematically summarise the current understanding of the molecular mechanisms and regulatory networks of RNA modifications in the female reproductive physiology and to evaluate their pathological implications in obstetric and gynaecologic disorders. Methods: We conducted a comprehensive literature review, synthesising findings from high-throughput sequencing studies, functional experiments and clinical investigations. The review integrates evidence across multiple RNA modification types, their regulatory enzymes (writers, erasers and readers) and their roles in physiological processes (germ cell development, oocyte maturation, embryogenesis and endometrial function) and pathological conditions (gynaecologic cancers, preeclampsia, endometriosis, polycystic ovary syndrome and premature ovarian insufficiency). Results: RNA modifications function as dynamic and reversible regulators that orchestrate key reproductive events, including primordial germ cell differentiation, oocyte meiosis, the maternal-to-zygotic transition, the establishment of uterine receptivity, and placental development. These modifications operate through coordinated writer–eraser–reader networks that fine tune transcripts’ stability, translation efficiency and RNA decay. The dysregulation of these epitranscriptomic networks is strongly implicated in the pathogenesis of gynaecologic malignancies (cervical, ovarian, endometrial cancers and choriocarcinoma), pregnancy-related disorders (preeclampsia, gestational diabetes mellitus and recurrent miscarriage), reproductive endocrine disorders (polycystic ovary syndrome and premature ovarian insufficiency) and benign gynaecological conditions (endometriosis and adenomyosis). Emerging evidence also reveals complex crosstalk among RNA modifications, such as cooperative interactions between m⁶A and m⁵C in translation regulation and antagonistic relationships between m⁶A and A-to-I editing. Conclusions: RNA modifications represent an essential and multifaceted regulatory layer in female reproduction, with broad implications for disease pathogenesis. Their unique reversibility and context-dependent functions offer promising opportunities for the development of diagnostic biomarkers and targeted therapeutic interventions. Future researchers should prioritise integrated multi-omics approaches, enhanced human-relevant models and clinical translation to fully realise the potential of epitranscriptomic medicine in reproductive health. Full article

Taraxacum kok-saghyz (TK), the rubber dandelion, is an emerging crop offering potential for sustainable natural rubber production independent of tropical climates. Successful domestication of TK requires a mechanistic understanding of its reproductive biology, yet floral anatomy, sporogenesis, and gametogenesis remain poorly characterized. We hypothesized that TK’s reproductive development follows the general patterns of sexually reproducing diploid Taraxacum species and other Asteraceae, distinguishable from the irregular meiosis reported in apomictic taxa. Here, using light and scanning electron microscopy across multiple developmental stages, we describe the floral and inflorescence anatomy, as well as sporogenesis and gametogenesis in TK. Anther development in TK predominantly follows the simultaneous microsporogenesis pattern, typical of eudicots, producing regular tetrahedral tetrads. Notably, we also observed occasional successive-type events resulting in dyads and tetragonal tetrads, indicating a previously unreported developmental variation within the species, culminating in mature tricellular pollen. We detail key reproductive structures, including anther wall layers, ovary mesophyll differentiation, and the presence of a micropylar obturator. The meiotic behavior and gametophyte development observed in TK are consistent with those of diploid, sexually reproducing Taraxacum species and other members of the Asteraceae, in contrast to the irregular meiosis reported in Taraxacum apomictic taxa. These newly described morphoanatomical details on reproductive aspects will inform breeding strategies and advance our understanding of pollination, fertilization, and seed development in TK. Full article

Background/Objectives: Chlamydia trachomatis (CT) infection is one of the most prevalent sexually transmitted infections (STIs) worldwide and has been consistently associated with adverse reproductive outcomes, including female infertility. However, the molecular mechanisms underlying this association remain incompletely understood. This study aimed to investigate whether genes previously associated with female infertility display altered expression patterns in response to CT infection by reanalyzing publicly available transcriptomic data derived from a human in vitro infection model. Methods: An integrative in silico approach was employed. A curated list of 106 genes associated with female infertility was compiled from publicly available databases and integrated with transcriptomic data from the Gene Expression Omnibus (GEO) dataset GSE109428, which profiles primary human fallopian tube mesenchymal cells infected in vitro with CT serovar L2. Gene expression changes were evaluated at two time points (24 and 48 h post-infection) by comparing infected cells with uninfected control samples, followed by functional and phenotype enrichment analyses. Results: One female infertility-associated gene (AKAP12) was consistently dysregulated at both 24 and 48 h post-infection. In addition, fourteen genes (ANAPC4, BMP1, BNC2, BTG4, EFHD1, FBXO43, INHBB, PATL2, SCARB1, SND1, SYNE1, TRIP13, TTC28, and TUBA1C) became significantly dysregulated exclusively at 48 h post-infection, indicating a time-dependent host transcriptional response to CT infection. Functional and phenotype enrichment analyses revealed associations with biological processes related to embryonic development and meiosis, as well as phenotypes linked to female infertility. These enriched terms were supported by a small subset of genes and were therefore interpreted cautiously. Conclusions: Overall, these findings suggest that CT infection modulates the expression of several infertility-associated genes and may influence biological pathways critical for female reproductive function. While exploratory, this study provides a molecular context that aligns with previously reported associations between CT infection and female infertility. Full article

Primary ovarian insufficiency (POI) affects up to 3% of reproductive-aged women and is a critical yet underrecognized contributor to infertility and systemic accelerated aging. While most cases remain idiopathic, advances in genomics increasingly reveal a genetic basis, implicating pathways that govern DNA repair, meiosis, chromosomal stability, and folliculogenesis. This review synthesizes the multifactorial etiology of POI, integrating genetic contributions with emerging evidence on epigenetic dysregulation, mitochondrial dysfunction, and environmental influences such as toxins and lifestyle factors. These mechanisms converge on core cellular processes, driving premature follicular depletion and shortening reproductive lifespan. We also highlight racial and ethnic disparities in POI prevalence and research representation, alongside the profound psychosocial burden experienced by affected individuals. Addressing these challenges through integrative strategies that unite mechanistic insight with equity is essential, not only for improving POI care but also for advancing precision approaches to ovarian aging and safeguarding reproductive health across the lifespan. Full article

In the filamentous fungus Neurospora crassa, a gene not having a pairing partner during meiosis is seen as a potential intruder and is targeted by a mechanism called meiotic silencing by unpaired DNA (MSUD). MSUD employs core RNA interference (RNAi) components such as the SMS-2 Argonaute, which uses small interfering RNAs (siRNAs) as guides to seek out mRNAs from unpaired genes for silencing. In Drosophila melanogaster, the heat shock protein 70 (Hsp70) chaperone system facilitates the conformational activation of an Argonaute and allows it to load siRNAs. Here, our results demonstrate that an Hsp70 protein in Neurospora interacts with SMS-2 and mediates the silencing of unpaired genes. Full article

The unicellular ciliate Paramecium caudatum undergoes a developmental transition from asexual binary fission to sexual reproduction during its mature stage. This transition is triggered by mating interactions between cells of complementary mating types, leading to aggregate formation, mating pairs, and the meiotic division of micronuclei. Although calcium-driven EF-hand kinases have been implicated as mating type proteins, the spatiotemporal dynamics of calcium signaling during conjugation have not been comprehensively characterized. In this study, we established a behavioral assay to isolate committed cells from aggregates immediately after mating onset, and developed an experimental system to monitor intracellular calcium fluctuations specifically expressed in these cells. By combining Ca²⁺/EGTA buffering and microinjection approaches, we manipulated extracellular and intracellular calcium levels and confirmed the continuous requirement of calcium ions for conjugation-specific functions. Two significant findings emerged. First, we identified, for the first time, a calcium atlas covering the entire cell, with ascending centers localized in the anterior, oral apparatus, and posterior regions. The calcium/Indo-1-AM fluorescence peaked at 6 h after mating initiation and declined gradually, but persisted until conjugation was completed at ~48 h. Second, we demonstrated that distinct intracellular calcium thresholds are required for each stage of mating, including maintenance of mating activity, commitment of micronuclei to meiosis, and two-stepwise formation of mating pairs. These thresholds function as regulatory checkpoints that coordinate subcellular localization and stage synchronization. Collectively, our findings highlight calcium ions as pivotal regulators of conjugation in Paramecium and propose a novel framework, the Paramecium calcium atlas, for understanding the cellular and molecular mechanisms underlying sexual reproduction in ciliates. Full article