ArticleAnimals : an open access journal from MDPI2026
Whole-Transcriptome Landscape Deciphers a ceRNA-Mediated "De-Repression-Activation" Circuit Governing Continuous Estrus in Ovine.
Article in Animals : an open access journal from MDPI, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
(1) Background: Seasonal breeding constraints represent a long-standing barrier to efficient sheep production worldwide. Small Tail Han sheep, a Chinese indigenous breed that exhibits year-round estrus independent of photoperiod, offers a unique natural model for investigating the regulatory mechanisms underlying estrus cyclicity-yet the molecular basis of this remarkable trait remains largely unexplored. This study therefore aimed to compare ovarian whole-transcriptome profiles between Small Tail Han sheep (year-round estrus) and Ujumqin sheep (seasonal estrus) during estrus and diestrus. Specifically, we sought to characterize breed-specific transcriptional response strategies, identify key miRNAs associated with continuous estrus, and construct ceRNA networks that mediate ovarian estrous cycle regulation. (2) Methods: To address these objectives, we profiled ovarian transcriptomes of Small Tail Han sheep (year-round estrus) and Ujumqin sheep (seasonal estrus) during both estrus and diestrus (12 samples total) using whole-transcriptome sequencing, systematically characterizing the expression landscapes of mRNAs, miRNAs, lncRNAs and circRNAs. Through differential expression analysis, GO/KEGG functional enrichment, multi-tiered miRNA screening, and ceRNA network construction, we compared the transcriptional response strategies between the two breeds. (3) Results: Our findings revealed two unexpected and divergent patterns. Small Tail Han sheep showed 1881 differentially expressed mRNAs between estrus and diestrus, 82-fold more than the 23 in Ujumqin sheep, suggesting a broader mRNA-level transcriptional response in the year-round estrus breed. circRNAs were predominantly up-regulated (80-85%) in both breeds, while mRNAs and lncRNAs were predominantly down-regulated, uncovering a conserved "circRNA-up, mRNA-down" regulatory logic across breeds. Multi-tiered screening identified 38 "brake-releaser" miRNAs (high in diestrus, down-regulated in estrus) and 21 "accelerator" miRNAs (low in diestrus, up-regulated in estrus), which together constitute a "de-repression-activation" dual regulatory mode. ceRNA network analysis further revealed a clear functional stratification: conserved core miRNAs targeted "sensor" pathways (cAMP, PI3K-Akt, MAPK), whereas accelerator miRNAs specifically targeted "executor" pathways (estrogen signaling, progesterone-mediated oocyte maturation, Hippo signaling). Network topology analysis pinpointed miR-199a-5p, miR-204-3p and miR-199b as the core hubs bridging the two regulatory modules. (4) Conclusions: Taken together, our findings redefine the molecular basis of year-round estrus-moving beyond single-gene mutations or overexpression to an enhanced global transcriptomic responsiveness of the ovary. This work provides a fresh conceptual framework for understanding the divergence of reproductive strategies in sheep and offers actionable candidate targets for genetic improvement of continuous estrus traits.
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