Integrative transcriptomic analysis reveals alternative splicing complexity and transcriptomic diversity in porcine placentas across altitudes.

Abstract

High-altitude hypoxia provides a natural laboratory for studying adaptation in plateau mammals. As an interface for oxygen and nutrient exchange, placenta plays a critical role in fetal development. While high-altitude adaptation in systemic physiological responses and cardiopulmonary tissues has been well-studied, a comprehensive landscape of porcine placental transcriptomic diversity and alternative splicing (AS) complexity across altitudes remains lacking. Here, we integrated Iso-Seq and RNA-Seq to profile placental transcriptomes from placentas of 3 pig breeds across altitudes: the Diannan small-ear pig (DSE ~500 m), the Baoshan pig (BS ~1500 m), and the Changdu Tibetan Pig (CT ~3500 m). We identified 39,776 full-length transcripts, including 25,471 novel ones, significantly enhancing pig genome annotation. Additionally, 24,879 AS events from 8,390 AS genes were detected, with skipping exon (SE) as the most prevalent AS type. Differential expression (DE) and differential alternative splicing (DAS) analyses highlighted key DEGs (IGF1, GHR, RASGRP4, MECOM, SPP1), as well as DAS genes (HIF1A, HSPA8, RHOA, HMGCR, PLAGL1), which may be implicated in placental adaptation to high-altitude conditions. This study provides a comprehensive analysis of the transcriptomic diversity and AS complexity in porcine placentas across altitudes, laying a foundation for future investigations into the molecular mechanisms underlying high-altitude adaptation in plateau mammals.