Molecular Reproduction and Development最新文献

{"title":"Metabolic Remodeling of the Fibrotic Niche: Implications of Finerenone for Ovarian Insufficiency and Beyond","authors":"Kuan-Hao Tsui, Chia-Jung Li","doi":"10.1002/mrd.70126","DOIUrl":"10.1002/mrd.70126","url":null,"abstract":"<p>The recent study by Lin et al. demonstrates that the antifibrotic drug finerenone restores folliculogenesis and fertility in models of premature ovarian insufficiency (POI) by reversing ovarian stromal fibrosis (Lin et al. <span>2026</span>). While the structural remodeling of extracellular matrix (ECM) has rightly attracted attention, an equally compelling dimension of this work lies in the metabolic reprogramming of the ovarian microenvironment. Fibrosis is not merely a mechanical pathology; it is a metabolically active process sustained by altered cellular energetics, redox imbalance, and nutrient flux. The findings by Lin et al. therefore, invite a broader pharmacological reconsideration: can modulation of tissue metabolism reverse organ failure by reshaping the fibrotic niche?</p><p>Fibrotic tissues exhibit profound metabolic alterations. Activated fibroblasts and myofibroblasts undergo metabolic reprogramming reminiscent of the Warburg effect, favoring glycolysis even under normoxic conditions to sustain collagen synthesis and proliferative signaling 4. Increased glycolytic flux supports biosynthetic pathways required for ECM deposition, while mitochondrial dysfunction and oxidative stress amplify profibrotic signaling cascades, including TGF-β activation (Henderson et al. <span>2020</span>).</p><p>In the ovary, fibrosis-associated metabolic disruption extends across multiple interrelated axes. First, progressive ECM accumulation increases interstitial diffusion distances, impairing oxygen delivery to follicular units. Hypoxic microenvironments, in turn, stabilize HIF-1α, which shifts cellular metabolism toward anaerobic glycolysis and further suppresses mitochondrial oxidative phosphorylation—creating a self-reinforcing cycle of metabolic deterioration (Hamanaka and Chandel <span>2010</span>). Second, fibrotic stiffening of the ovarian stroma mechanically alters cell behavior through mechanotransduction pathways, particularly YAP/TAZ signaling, which promotes glycolytic reprogramming and fibroblast activation while suppressing mitochondrial biogenesis (Cai et al. <span>2021</span>; Dupont et al. <span>2011</span>). Third, impaired mitochondrial efficiency in granulosa cells compromises their capacity to support oocyte maturation. Granulosa cells normally supply oocytes with pyruvate, amino acids, and antioxidant metabolites essential for mitochondrial ATP synthesis; dysregulation of this metabolic coupling is associated with diminished oocyte quality and follicular arrest (Dupont et al. <span>2011</span>; Sutton-McDowall et al. <span>2010</span>). Fourth, increased ROS generation within the fibrotic niche directly damages mitochondrial DNA and impairs electron transport chain function, further reducing bioenergetic capacity and sensitizing granulosa cells to apoptosis (Prasad et al. <span>2016</span>).</p><p>Importantly, fibrosis alters not only the metabolism of fibroblasts but also that of neighboring parenchymal cells. In the ovary, ","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"93 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.70126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148278031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Placental Dysfunction in Cloned Pigs Linked to Impaired Trophoblast Adhesion and Vascular Development","authors":"Xia Zhang,&nbsp;Xin Liu,&nbsp;Cheng-Li Dou,&nbsp;Xiao-Li Liu,&nbsp;Tian Xu,&nbsp;Weiwei Wang,&nbsp;Jingjing Zhang,&nbsp;Hainan He,&nbsp;Linhui Wu,&nbsp;Mei Yu,&nbsp;Yi-Liang Miao","doi":"10.1002/mrd.70122","DOIUrl":"10.1002/mrd.70122","url":null,"abstract":"<div>\u0000 \u0000 <p>Animal cloning, while promising for livestock breeding and genetic improvement, is hampered by low efficiency largely due to placental abnormalities. This study investigated this issue in cloned pigs at the 35th day of gestation, where a 69.8% developmental abnormality rate was observed. Morphological analyses revealed structural defects in placentas from failed pregnancies, including delayed fold development and abnormal areolae formation, coupled with reduced endometrial glands and maternal-side blood vessels. Immunohistochemistry demonstrated impaired placental function, evidenced by aberrant E-cadherin expression compromising trophoblast adhesion, and significantly reduced glycogen/polysaccharide secretion. Furthermore, Plet1 expression was disrupted. Transcriptomic profiling indicated that upregulated genes were enriched in cell-cell tight junctions, while downregulated genes were associated with oxygen binding, oxidative stress, stromal differentiation, and vascular development. Cross-species comparison with cloned mice suggested conserved genetic mechanisms underlying placental defects. These findings provide a crucial theoretical foundation for elucidating the mechanisms of placental failure in animal cloning and for developing strategies to enhance its efficiency.</p>\u0000 </div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"93 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental Expression of Transcription Factors and Wnt Ligands in Sponge Halisarca Dujardinii","authors":"Ilya Borisenko,&nbsp;Dmitry Shaporev,&nbsp;Alexander V. Ereskovsky","doi":"10.1002/mrd.70121","DOIUrl":"10.1002/mrd.70121","url":null,"abstract":"<div>\u0000 \u0000 <p>Understanding the molecular mechanisms that guided early animal evolution is a central challenge of evolutionary developmental biology. Sponges (Porifera), as one of the earliest-branching metazoan lineages, are crucial for reconstructing the ancestral genetic toolkit for development. Here, we present the first transcriptomic analysis of embryogenesis in the demosponge <i>Halisarca dujardinii</i>, characterizing gene expression across three key stages: cleavage, blastula, and prelarva. We identified significant transcriptional shifts, including upregulation of cadherins during blastula formation, suggesting the establishment of adherens junctions, and a wave of kinase expression in the prelarva. Furthermore, we phylogenetically classified and analyzed the developmental expression of 186 transcription factors from the zinc finger, homeobox, Forkhead, and T-box families. Strikingly, spatial expression analysis revealed that Wnt ligands and T-box genes are expressed in complementary domains along the embryonic anterior-posterior axis, with <i>HduWntL</i> specifically marking the future posterior pole from the blastula stage. Our results demonstrate that despite its morphological simplicity, <i>H. dujardinii</i> employs a complex repertoire of developmental transcription factors and signaling molecules, and provides evidence for the early specification of the primary body axis, offering new insights into the evolution of developmental mechanisms in metazoans.</p>\u0000 </div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"93 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Fluorescence-Activated Cell Sorting on Boar Sperm Motility Subpopulations and In Vitro Embryo Development","authors":"Isabel Rodriguez,&nbsp;Tyler Weide,&nbsp;Caleigh E. Grote,&nbsp;Alexandra Keller,&nbsp;Catarina Bittencourt,&nbsp;Emily Schoelerman,&nbsp;Ian Shofner,&nbsp;Aileen F. Keating,&nbsp;Bethany K. Redel,&nbsp;Karl Kerns","doi":"10.1002/mrd.70123","DOIUrl":"10.1002/mrd.70123","url":null,"abstract":"<p>Flow cytometric sorting can be used to select sperm subpopulations with defined physiological or molecular traits; however, the impact of sorting on sperm function and subsequent embryo development in the porcine model remains unresolved. The objective of this study was to evaluate the effect of fluorescence-activated cell sorting (FACS) on boar sperm motility and developmental competence following in vitro fertilization (IVF). Pooled semen from boars was divided into sorted and unsorted (control) treatments and analyzed for motility and kinematic parameters using computer-aided sperm analysis (CASA) with both population-level (conventional, population-averaged) metrics and single-cell track data collected before and after sorting. Oocytes were fertilized with either treatment, and cleavage (≥ 2-cell stage) and blastocyst development were evaluated. Cleavage and blastocyst percentages were reduced in the sorted (48.8% ± 9.9% and 8.5% ± 4.2%) compared with control (92.2% ± 1.5% and 28.4% ± 2.8%, respectively; <i>p</i> &lt; 0.001) group. Population-level CASA revealed statistically significant but biologically modest changes in motility and kinematic parameters following sperm sorting. In contrast, single-cell CASA coupled with <i>k</i>-means clustering identified four distinct motility subpopulations and demonstrated that sorting redistributed existing motility states, characterized by depletion of fast, progressive sperm and enrichment of less energetically demanding populations. These findings suggest that FACS alters the composition of sperm motility subpopulations, alongside a marked reduction in post-fertilization developmental competence in porcine IVF.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"93 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.70123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Determination in Sponges","authors":"Jose M. Lorente-Sorolla,&nbsp;Ana Riesgo","doi":"10.1002/mrd.70115","DOIUrl":"10.1002/mrd.70115","url":null,"abstract":"<p>Sex determination in Porifera remains one of the least understood aspects of early metazoan biology despite the group's key phylogenetic position. Sponges display exceptional diversity in sexual systems—ranging from stable gonochorism to sequential hermaphroditism and sex reversal—yet lack morphological dimorphism and any discrete gonadal structures, blurring the boundary between sex determination and gametogenesis. Here we synthesize current knowledge on sexual systems, environmental and genetic influences on sexual fate, and the evolutionary origins of sexual systems in sponges. Evidence for environmental modulation is substantial, particularly temperature-driven shifts in sex ratios and reproductive timing, but environmental sex determination remains unsupported by causal evidence yet. Conversely, conserved molecular components of metazoan sex-determining pathways, such as <i>fem-1</i> and <i>Dmrt</i> genes, are present in several sponge lineages, though their functional roles remain unresolved. We also evaluate the hypothesis that microbial symbionts contribute to sexual allocation by buffering the energetic costs of gametogenesis. Overall, sponges exhibit an evolutionarily labile system in which sexual fate may emerge from the interaction of conserved genetic modules, environmental cues, and physiological constraints. Clarifying these mechanisms will be essential for understanding the origins of sex determination in Metazoa and for predicting reproductive resilience under environmental change.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"93 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Preface for Special Issue “Reproduction in Sponges: Diversity, Strategies, and Regulation”","authors":"Alexander V. Ereskovsky,&nbsp;Andrey I. Lavrov","doi":"10.1002/mrd.70125","DOIUrl":"10.1002/mrd.70125","url":null,"abstract":"&lt;p&gt;Sponges have long fascinated biologists, and they remain central to Evo-Devo research. This status rests on their phylogenetic position as one of the early-diverging metazoan groups and on their unique anatomical and histological organization. Despite numerous debates regarding who diverged first, Porifera or Ctenophora, sponges remain a key group for understanding such fundamental questions as the origin of animal multicellularity and mechanisms of tissue integration, evolution of epithelium and nervous system, etc. From the Evo-Devo point of view, studies of sponges are crucial to shed light upon the nature of the somatic/germ line segregation in animals, the origin and early evolution of gametogenesis, embryonic and postembryonic development, asexual reproduction, regeneration, and morphogenesis itself (Lanna &lt;span&gt;2015&lt;/span&gt;; Colgren and Nichols &lt;span&gt;2019&lt;/span&gt;).&lt;/p&gt;&lt;p&gt;Despite more than 170 years of sponge developmental research (Ereskovsky &lt;span&gt;2010&lt;/span&gt;; Cajado and Lanna, this issue), many obscure and unexplored topics remain in the developmental biology of these ancient animals. While sharing the basic features of reproduction (gametogenesis, fertilization, development from zygote, active cell movements during embryonic development, etc.) with eumetazoans, sponges demonstrate a great diversity of reproduction strategies and regulation, morphogenesis, and cell behavior, many of which are unique for the phylum. This special issue, “Reproduction in Sponges: Diversity, Strategies, and Regulation,” aims to present some of these poorly explored aspects in the developmental biology of Porifera.&lt;/p&gt;&lt;p&gt;Sponges demonstrate remarkably diverse sexual systems, ranging from stable gonochorism to sequential hermaphroditism and sex reversal (Sarà. &lt;span&gt;1993&lt;/span&gt;). Surprisingly, the sexual system can be labile even with a single species being changed from year to year (Fell and Jacob &lt;span&gt;1979&lt;/span&gt;). Furthermore, mechanisms of sex determination in sponges are poorly documented because studies are at least partially hindered by the absence of sexual dimorphism and structurally separated gonads in these animals. Lorente-Sorolla and Riesgo contribute a review that synthesizes the current knowledge on the sexual systems, environmental and genetic cues driving sexual fate, and the evolutionary origins of sexual conditions in sponges. They scrupulously analyze the scarce evidence of environmental and genotypic sex determination in sponges, giving proper attention to physiological and organizational features of these animals. Overall, Lorente-Sorolla and Riesgo argue that sponges exhibit an evolutionarily labile system in which sexual fate may emerge from the interaction of conserved genetic modules, environmental cues, and physiological constraints.&lt;/p&gt;&lt;p&gt;In turn, Cajado and Lanna present a wide and unique historical panorama of studies of reproduction and development in calcareous sponges for the last 200 years. Scrutinizing over 200 articles ran","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"93 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tris(2,3-dibromopropyl) Isocyanurate Modulates Oxidative Stress and Autophagy-Related Pathways in Mouse GC-1 Spermatogenic Cells In Vitro","authors":"Dominika Szlachcikowska,&nbsp;Bartosz Skóra,&nbsp;Anna Tabęcka-Łonczyńska","doi":"10.1002/mrd.70118","DOIUrl":"10.1002/mrd.70118","url":null,"abstract":"<div>\u0000 \u0000 <p>Tris-2,3-dibromopropyl isocyanurate (TBC), a brominated flame retardant widely used in industrial applications, raises increasing concerns due to its potential reproductive toxicity. While the role of apoptosis in TBC-induced cytotoxicity is partially understood, its effects on autophagy in reproductive cells remain underexplored. Therefore, the present study aimed to determine the impact of TBC on autophagy-related processes in GC-1 (spg) spermatogenic cell line as an in vitro model of testis-derived cells. Our findings demonstrate that TBC significantly reduces cellular metabolic activity in a time-dependent manner. Molecular analysis revealed an upregulation of PPARγ gene expression, accompanied by a decrease in phosphorylated mTOR (p-mTOR) levels and a concurrent increase in phosphorylated IRE1 (p-IRE1), indicating activation of endoplasmic reticulum (ER) stress pathways. Furthermore, TBC exposure was associated with modulation of autophagy-related markers, suggesting a potential adaptive or compensatory cellular response to stress conditions. Cell cycle analysis showed arrest in the G0/G1 phase, while ROS quantification indicated elevated reactive oxygen species production upon treatment. Collectively, our data suggest that TBC disrupts cell homeostasis through ER stress-associated signaling, oxidative stress, and cell cycle regulation, which may contribute to its potential reproductive toxicity.</p>\u0000 </div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"93 5","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148032904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leucine Promotes Mouse Primordial Follicle Activation Via the PI3K/Akt Signaling Pathway","authors":"Yating Huang,&nbsp;Hongwei Wei,&nbsp;Wenbo Zhang,&nbsp;Zhijuan Wang,&nbsp;Weiyong Wang,&nbsp;Yanli Sun,&nbsp;Hanyu Chu,&nbsp;Meijia Zhang,&nbsp;Xiaodan Zhang","doi":"10.1002/mrd.70120","DOIUrl":"10.1002/mrd.70120","url":null,"abstract":"<div>\u0000 \u0000 <p>Premature ovarian insufficiency (POI) patients usually have a few residual dormant primordial follicles that are difficult to activate. We investigated the effects of branched-chain amino acids (BCAAs) on mouse primordial follicle activation. Leucine, but not isoleucine and valine, promoted primordial follicle activation in the cultured neonatal mouse ovaries. Furthermore, leucine significantly elevated the levels of phosphorylated protein kinase B (p-Akt) and phosphorylated forkhead Box O3a (p-FOXO3a), and increased the number of oocytes exhibiting nuclear export of FOXO3a in mouse ovaries. LY294002 and PI3K-IN-1, the inhibitors of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, reversed the promoting effects of leucine on mouse primordial follicle activation. Importantly, intraperitoneal injection of leucine in 3-day-old neonatal mice and oral administration of leucine in 21-day-old mice with or without cyclophosphamide treatment significantly increased the number of growing follicles. Thus, leucine activates mouse primordial follicles through the PI3K/Akt pathway. Leucine may be a potential oral supplement for treating infertility in POI patients with residual dormant primordial follicles.</p>\u0000 </div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"93 5","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148032891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"93 5","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148094667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"93 5","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148094666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}