12 / 2026-01-29 17:06:47

Research on the genetic and molecular mechanisms underlying the higher reproductive capacity of Tibetan populations in high-altitude

high altitude,adaptation,placenta,Reproduction

前沿论坛 > 生命组学技术

Reproduction is a central component of human fitness and is particularly challenged by hypoxic environments, which are associated with increased miscarriage rates and fetal growth restriction. Tibetans, as the earliest population to colonize and permanently inhabit the Qinghai–Tibet Plateau, exhibit higher reproductive success and more favorable birth outcomes under chronic hypoxia, yet the underlying genetic and molecular mechanisms remain poorly understood. To investigate the genetic basis of reproductive adaptation to high-altitude hypoxia, we conducted a comprehensive analysis of reproductive phenotypes and genome-wide association data from over 2,000 mother-newborn pairs. Compared with Han individuals delivering at similar altitudes, Tibetan mothers showed significantly improved reproductive performance, a pattern consistent with polygenic adaptation rather than single-locus effects. To further assess the functional relevance of hypoxia-adaptation genes, we examined EPAS1 heterozygous knockout mice under hypoxic conditions. These mice exhibited higher birth rates and enhanced embryonic developmental outcomes, suggesting a protective role of partial EPAS1 modulation in hypoxia-associated reproduction. In the tissue and molecular levels, comparative histological and transcriptomic analyses of placental samples from high-altitude populations revealed more favorable placental architecture and gene expression profiles in Tibetans. Notably, high-altitude adaptation candidate genes showed potential regulatory roles in placental function, although their precise mechanisms require further investigation. Together, our findings elucidate the phenotypic, genetic, and placental features underlying long-term reproductive adaptation to high-altitude environments, providing new insights into how natural selection shapes human reproductive fitness under extreme ecological pressures.