Lactational high weight loss impairs follicular development by causing mitochondrial dysfunction of ovarian cells in sows and mitigated by butyrate supplement

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

In modern sows, lactational high weight loss (HWL), caused by the large litter size and inadequate feed intake, has a negative effect on follicular development after weaning, resulting in poor reproductive performance subsequent parity. However, underlying mechanism remains unclear. This research aimed to explore that sows HWL during lactation damages attempt improve function treating with butyrate. Four multiparous sister were chosen build model for lactating through restriction final week of 21-day lactation. Spatially transcriptomics (ST) tissue immunofluorescent staining then utilized antral follicles ovarian surface search differentially expressed genes proteins among different cell types. Subsequently, mouse assay, including staining, transmission electron microscopy, hormone detection western blot, conducted verify findings investigate butyrate mice. Based transcriptomic analysis, granulosa cells, theca stromal cells examined. The revealed disturbs mitochondrial transport chain steroidogenesis all three types downregulating expression NDUFB3, SDHB, CYCS, COX8A CYP19A1, as well upregulating STAR, CYP11A1 CYP17A1. Furthermore, results from assays demonstrated causes apoptosis alters sex secretion impairing disordering key enzymes while these effects partially mitigated dysfunction abnormal induced harm weaning which could be alleviated

Language: Английский

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Single-cell and spatiotemporal profile of ovulation in the mouse ovary

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 22, 2024

Ovulation is a spatiotemporally coordinated process that involves several tightly controlled events, including oocyte meiotic maturation, cumulus expansion, follicle wall rupture and repair, ovarian stroma remodeling. To date, no studies have detailed the precise window of ovulation at single-cell resolution. Here, we performed parallel RNA-seq spatial transcriptomics on paired mouse ovaries across an time course to map spatiotemporal profile cell types. We show major types exhibit time-dependent transcriptional states enriched for distinct functions specific localization profiles within ovary. also identified gene markers ovulation-dependent validated these using orthogonal methods. Finally, cell-cell interaction analyses identify ligand-receptor pairs may drive ovulation, revealing previously unappreciated interactions. Taken together, our data provides rich comprehensive resource murine can be mined discovery by scientific community.

Language: Английский

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Granulosa Cell‐Layer Stiffening Prevents Escape of Mural Granulosa Cells from the Post‐Ovulatory Follicle

Advanced Science, Journal Year: 2024, Volume and Issue: 11(33)

Published: July 1, 2024

Ovulation is vital for successful reproduction. Following ovulation, cumulus cells and oocyte are released, while mural granulosa (mGCs) remain sequestered within the post-ovulatory follicle to form corpus luteum. However, mechanism underlying confinement of mGCs has been a longstanding mystery. Here, in vitro vivo evidence provided demonstrating that stiffening mGC-layer serves as an evolutionarily conserved prevents from escaping follicles. The results spatial transcriptome analysis experiments reveal focal adhesion assembly, triggered by LH (hCG)-cAMP-PKA-CREB signaling cascade, necessary stiffening. Disrupting assembly through RNA interference failure, mGC escape, subsequent development abnormal luteum characterized decreased cell density or cavities. These findings introduce novel concept "mGC-layer stiffening", shedding light on escape follicle.

Language: Английский

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Hormonally-regulated KCTD14 Expression Is Higher in Oocytes from Antral Follicles Compared to Those from Preantral Follicles in Mice, with Implications in Fertility.

PubMed, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Language: Английский

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Multi-Omics Approaches Uncovered Critical mRNA–miRNA–lncRNA Networks Regulating Multiple Birth Traits in Goat Ovaries

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12466 - 12466

Published: Nov. 20, 2024

The goat breeding industry on the Tibetan Plateau faces strong selection pressure to enhance fertility. Consequently, there is an urgent need develop lines with higher fertility and adaptability. ovary, as a key organ determining reproductive performance, regulated by complex transcriptional network involving numerous protein-coding non-coding genes. However, molecular mechanisms of mRNA-miRNA-lncRNA regulatory in ovaries remain largely unknown. This study focused histology differential mRNA/miRNA/lncRNA between Chuanzhong black (CBG, high productivity, multiple births) (TG, adaptability, single birth) ovaries. Histomorphological analysis showed that medulla proportion CBG was significantly reduced compared TG. RNA-Seq small identified 1218 differentially expressed (DE) mRNAs, 100 DE miRNAs, 326 lncRNAs, which were mainly enriched ovarian steroidogenesis, oocyte meiosis, biosynthesis amino acids protein digestion, absorption signaling pathways. Additionally, five interaction networks regulating performance identified, including

Language: Английский

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Comparison of Steroidogenic and Ovulation-Inducing Effects of Orthosteric and Allosteric Agonists of Luteinizing Hormone/Chorionic Gonadotropin Receptor in Immature Female Rats

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(23), P. 16618 - 16618

Published: Nov. 22, 2023

Gonadotropins, including human chorionic gonadotropin (hCG), are used to induce ovulation, but they have a number of side effects, ovarian hyperstimulation syndrome (OHSS). A possible alternative is allosteric luteinizing hormone (LH)/hCG receptor agonists, the compound TP4/2 we developed, which remains active when administered orally. The aim was study effectiveness (orally, 40 mg/kg) as an ovulation inducer in FSH-stimulated immature female rats, compared with hCG (s.c., 15 IU/rat). stimulated progesterone production and corpus luteum formation; time-dependently increased expression steroidogenic genes (Star, Cyp11a1, Cyp17a1) involved regulation (Adamts-1, Cox-2, Egr-1, Mt-1); content metalloproteinase ADAMTS-1 ovaries. These effects were similar those hCG, although some cases less pronounced. TP4/2, contrast maintained normal LH levels LH/hCG gene, indicating preservation sensitivity LH, did not cause sustained increase vascular endothelial growth factor-A OHSS. Thus, effective that, unlike has lower risk OHSS resistance due its moderate stimulating effect on steroidogenesis.

Language: Английский

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Granulosa cell-layer stiffening prevents the granulosa cells from escaping the post-ovulatory follicle

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 8, 2024

ABSTRACT Ovulation is necessary for successful reproduction. After ovulation, cumulus cells and oocytes are released, while granulosa (GCs) remain trapped within the post-ovulatory follicle to form corpus luteum. However, mechanism underlying GC confinement has long been unclear. Here, we provide in vitro vivo evidence demonstrating that stiffening of GC-layer as an evolutionarily conserved hinders GCs from escaping follicles. Spatial transcriptome analysis reveals assembly focal adhesions primarily responsible this stiffening. Disrupting adhesion through RNA interference results release follicle, leading formation aberrant luteum with reduced cell density cavities. We also uncover LH (hCG) -cAMP-PKA-CREB signaling axis stimulates induce Our findings introduce a novel concept “GC-layer stiffening”, which offers valuable insights into factors prevent escape follicle.

Language: Английский

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Dynamic changes in cellular atlases and communication patterns within yak ovaries across diverse reproductive states unveiled by single-cell analysis

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Aug. 29, 2024

Yaks ( Bos grunniens ) exhibit exceptional adaptation to the challenging high-altitude environment of Qinghai-Tibetan plateau, making them sole bovine species capable thriving in such exreme conditions. Investigating cellular and molecular characteristics yak ovaries across different reproductive states is crucial for gaining insight into their ovarian functions. Herein, atlases were depicted by single-cell RNA-sequencing (scRNA-seq). The established identifying specific gene expression patterns various cell types, including granulosa cells, theca stromal smooth muscle endothelial glial cell, macrophages, natural killer proliferating cells. compositions vary among states. Furthermore, cells comprise six subtypes, while consist eight subtypes. distinct biological functions throughout two types aligned along respective pseudotime trajectories. Moreover, a cell-to-cell communication network was constructed within ovary, spanning three Notably, during estrus period, demonstrated more prominent interactions with other compared remaining

Language: Английский

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MicroRNA‐3061 downregulates the expression of PAX7/Wnt/Ca²⁺ signalling axis genes to induce premature ovarian failure in mice

Cell Proliferation, Journal Year: 2024, Volume and Issue: unknown

Published: June 3, 2024

Abstract The in‐depth mechanisms of microRNA regulation premature ovarian failure (POF) remain unclear. Crispr‐cas9 technology was used to construct transgenic mice. qPCR and Western blot detect the expression level genes. H&E staining were pathological phenotypes. We found that levels microRNA‐3061 significantly higher in granulosa cells (OGCs) POF mouse models than controls. miR‐3061 +/− /AMH‐Cre mice manifested symptoms POF. RNA‐Seq luciferase reporter assay confirmed PAX7 one target genes negatively regulated by (miR‐3061–5p). Moreover, mediated non‐canonical Wnt/Ca 2+ signalling pathway binding motifs promoters stimulate transcriptional activation Wnt5a CamK2a. In contrast, specific knock‐in OGCs downregulated inhibited downstream pathway. also discerned a correlation between mRNAs Wnt/Ca2+ E2 FSH patients examining gene follicular fluid‐derived exosomes women. overexpression induced proliferative inhibition ultimately suppressing transcription factor downregulating its

Language: Английский

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Subcellular Level Spatial Transcriptomics with PHOTON

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 14, 2024

The subcellular localization of RNA is closely linked to its function. Many species are partitioned into organelles and other compartments for storage, processing, translation, or degradation. Thus, capturing the spatial distribution would directly contribute understanding functions regulation. Here, we present PHOTON (Photoselection Transcriptome over Nanoscale), a method which combines high resolution imaging with throughput sequencing achieve transcriptome profiling at resolution. We demonstrate as versatile tool accurately capture target cell types

Language: Английский

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