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  <front>
    <journal-meta>
      <journal-title-group>
        <journal-title>Cosmological and Astrobiological Review</journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0000-0000</issn>
      <issn pub-type="epub">0000-0000</issn>
      <publisher>
        <publisher-name>SAPCRAA</publisher-name>
        <publisher-loc>Banja Luka, Bosnia and Herzegovina</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">1522</article-id>
      <article-id pub-id-type="doi">https://doi.org/10.65932/CAR-2024-1-5</article-id>
      <title-group>
        <article-title>Molecular carriers of transgenerational epigenetic inheritance in mammals: a comprehensive review and the tcmsi carrier-mechanism sufficiency framework</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Mendes</surname>
            <given-names>Rafael Souza</given-names>
          </name>
          <contrib-id contrib-id-type="orcid">https://orcid.org/0009-0006-2630-1030</contrib-id>
        </contrib>
      </contrib-group>
      <pub-date pub-type="epub">
        <day>30</day>
        <month>12</month>
        <year>2024</year>
      </pub-date>
      <volume>2</volume>
      <issue>1</issue>
      <fpage>57</fpage>
      <lpage>70</lpage>
      <self-uri xlink:href="https://www.sapcraa.com/article-preview/1522"/>
      <abstract>
        <p>Transgenerational epigenetic inheritance (TGEI) in mammals — the transmission of phenotype-relevant epigenetic information from an exposed F0 generation to unexposed F3 (maternal lineage) or F2 (paternal lineage) generations through germline mechanisms — has, in the 2016-2022 window, accumulated a substantial empirical literature spanning at least five candidate molecular carrier classes: residual DNA methylation surviving the two genome-wide reprogramming events, sperm-borne transfer-RNA-derived small RNAs (tsRNAs) and their post-transcriptional modifications, sperm microRNAs (miRNAs), retained histone posttranslational modifications at sperm-resistant loci, and higher-order chromatin-architecture features including topologically associating domains and centromeric heterochromatin organisation. Each carrier class has accumulated its own evidentiary profile across detection robustness, reprogramming-bypass mechanism, zygote-rescue causality, cross-species evolutionary conservation, and therapeutic-translation actionability. The literature has, however, been organised predominantly around specific phenomenological claims — paternal-diet metabolic inheritance, paternal-stress behavioural inheritance, Holocaust FKBP5 trauma transmission, gestational-famine epigenetic imprints — rather than around the molecular carriers themselves. The companion article in this series introduced the Mammalian Transgenerational Epigenetic Inheritance Evidence Index (MTEII) to evaluate the claim-level evidentiary strength of specific TGEI cases; the present review introduces, as the complementary original contribution, the Transgenerational Carrier-Mechanism Sufficiency Index (TCMSI), a normalised composite metric — bounded on [0,1] — that integrates five carrier-mechanism dimensions (detection robustness in mammalian germline, reprogramming-bypass mechanism specificity, demonstrated zygote-rescue causality, inter-species evolutionary conservation, and therapeutictranslation actionability) and returns a quantitative ranking of the five carrier classes on a metric explicitly designed to evaluate molecular-mechanism sufficiency rather than claim-level evidentiary support. Applied to the five canonical carrier classes, TCMSI returns the highest score for sperm tsRNAs and their DNMT2-mediated modifications (≈0.62), intermediate scores for sperm miRNAs (≈0.55) and residual DNA methylation (≈0.42), and lower scores for retained histone modifications (≈0.35) and higher-order chromatin architecture (≈0.28).</p>
      </abstract>
      <kwd-group kwd-group-type="author">
        <kwd>transgenerational epigenetic inheritance</kwd>
        <kwd>sperm tsRNAs</kwd>
        <kwd>sperm miRNAs</kwd>
        <kwd>DNA methylation reprogramming</kwd>
        <kwd>histone modifications</kwd>
        <kwd>chromatin architecture</kwd>
        <kwd>molecular carriers</kwd>
        <kwd>mammalian germline</kwd>
        <kwd>DNMT2</kwd>
        <kwd>evidentiary frameworks</kwd>
      </kwd-group>
    </article-meta>
  </front>
</article>
