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Overlapping and distinct fatty acid dysregulation in infertility and recurrent spontaneous abortion.

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Τίτλος: Overlapping and distinct fatty acid dysregulation in infertility and recurrent spontaneous abortion.
Συγγραφείς: Wei S; Department of Reproductive Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China., Li Y; Department of Reproductive Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.; Assisted Reproduction Center, Northwest Women's and Children's Hospital, Xi'an, Shaanxi, China., Luo P; Department of Reproductive Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China., Yang X; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China., Zheng PS; Department of Reproductive Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Πηγή: Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2026 Jun 12; Vol. 17, pp. 1866902. Date of Electronic Publication: 2026 Jun 12 (Print Publication: 2026).
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101555782 Publication Model: eCollection Cited Medium: Print ISSN: 1664-2392 (Print) Linking ISSN: 16642392 NLM ISO Abbreviation: Front Endocrinol (Lausanne) Subsets: MEDLINE
Imprint Name(s): Original Publication: [Lausanne : Frontiers Research Foundation]
Ιατρικοί όροι (MeSH): Abortion, Habitual*/metabolism , Abortion, Habitual*/blood , Fatty Acids*/blood , Fatty Acids*/metabolism , Infertility, Female*/metabolism , Infertility, Female*/blood, Fatty Acids, Omega-3/blood ; Fatty Acids, Omega-6/blood ; Antibodies, Antiphospholipid/blood ; Humans ; Female ; Pregnancy ; Retrospective Studies ; Adult ; Case-Control Studies
Περίληψη: Introduction: Infertility and recurrent spontaneous abortion (RSA) are common reproductive disorders with rising incidence. Both fatty acid (FA) metabolism and antiphospholipid antibodies (aPL) are known to be associated with reproductive outcomes. However, their interaction and distinct roles in infertility versus RSA remain poorly understood.
Methods: This retrospective study included 388 women (64 controls, 135 infertility cases, 189 RSA cases). FA profiles were measured from dried blood spots by gas chromatography. Candidate FAs were identified by FDR-corrected univariate analyses and refined by random forest. Core FAs were defined as the intersection of significant FAs and random forest-important variables. Associations between core FAs and aPL positivity were assessed by logistic regression. Mediation analysis used structural equation modeling.
Results: An elevated omega-6/omega-3 ratio and lower DPAn3 were seen in both infertility and RSA. Infertility also showed a broader decline in omega-3-related FAs (omega-3, EPA, DHA; all P < 0.05), while RSA featured higher behenic acid (P = 0.023). The omega-6/omega-3 ratio was positively associated with aPL positivity in both groups (infertility: adjusted OR = 3.51, 95% CI 2.24 - 5.91, P < 0.001; RSA: OR = 4.87, 95% CI 3.15 - 8.05, P < 0.001); DPAn3 was inversely associated with aPL positivity in both groups (infertility: P < 0.05; RSA: adjusted OR = 0.33, 95% CI 0.18 - 0.53, P < 0.001). In mediation analysis, aPL positivity partially mediated the relationship between the omega-6/omega-3 ratio (indirect effect 0.110, 30.7% mediated, P = 0.045) and DPAn3 (indirect effect 0.080, 40.1% mediated, P = 0.022) with RSA, but not with infertility.
Discussion: Infertility and RSA exhibit overlapping yet distinct FA profiles. aPL positivity partially mediates the associations of the omega-6/omega-3 ratio and DPAn3 with RSA, but not with infertility. These findings demonstrate metabolic and immunological heterogeneity associated with different adverse reproductive outcomes.
(Copyright © 2026 Wei, Li, Luo, Yang and Zheng.)
Competing Interests: The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References: Gynecol Endocrinol. 2022 Dec;38(12):1097-1103. (PMID: 36443944)
Anal Sci Adv. 2024 Jun 14;5(5-6):e2400002. (PMID: 38948320)
Front Nutr. 2022 Aug 01;9:903689. (PMID: 35978962)
Hypertens Res. 2020 May;43(5):412-421. (PMID: 31919480)
Am J Obstet Gynecol. 2022 Aug;227(2):246.e1-246.e11. (PMID: 35364062)
Isr Med Assoc J. 2023 Feb;25(2):131-136. (PMID: 36841983)
Genes Nutr. 2024 Aug 29;19(1):18. (PMID: 39210266)
Eur J Obstet Gynecol Reprod Biol. 2022 Aug;275:97-105. (PMID: 35779332)
Reprod Biol Endocrinol. 2015 Apr 26;13:37. (PMID: 25928197)
Hum Reprod Open. 2023 Mar 01;2023(2):hoad007. (PMID: 36959890)
Reprod Sci. 2023 Feb;30(2):408-427. (PMID: 35676498)
Front Endocrinol (Lausanne). 2024 Feb 26;15:1280760. (PMID: 38469148)
J Obstet Gynaecol Res. 2020 Aug;46(8):1310-1318. (PMID: 32500661)
iScience. 2024 Sep 24;27(10):111019. (PMID: 39429784)
Biomedicines. 2025 Nov 05;13(11):. (PMID: 41301804)
Autoimmun Rev. 2026 May;25(5):104040. (PMID: 41865949)
Arthritis Rheumatol. 2023 Oct;75(10):1687-1702. (PMID: 37635643)
Front Public Health. 2022 Aug 17;10:938343. (PMID: 36062133)
Hum Reprod. 2022 May 3;37(5):1037-1046. (PMID: 35147198)
BMC Pregnancy Childbirth. 2026 Feb 07;26(1):. (PMID: 41652374)
Nat Rev Rheumatol. 2017 Sep;13(9):548-560. (PMID: 28769114)
Endocrinology. 2018 Dec 1;159(12):3981-3992. (PMID: 30403782)
Lupus. 1993 Oct;2(5):319-23. (PMID: 8305926)
Placenta. 2024 Sep 26;155:100-112. (PMID: 39180926)
J Nutr Biochem. 2021 Dec;98:108813. (PMID: 34242722)
Reprod Biomed Online. 2019 Jan;38(1):95-99. (PMID: 30660386)
Front Nutr. 2024 Aug 29;11:1439599. (PMID: 39267857)
Naunyn Schmiedebergs Arch Pharmacol. 2026 Mar;399(6):8311-8326. (PMID: 41454956)
Am J Clin Nutr. 2019 Oct 1;110(4):823-831. (PMID: 31204771)
Lancet. 2021 May 1;397(10285):1658-1667. (PMID: 33915094)
Mol Cell Biochem. 2015 Mar;401(1-2):11-9. (PMID: 25413343)
Reprod Biol Endocrinol. 2022 Jul 25;20(1):107. (PMID: 35879714)
J Nutr Biochem. 2021 Oct;96:108784. (PMID: 34062269)
Hum Reprod Open. 2023 Mar 02;2023(1):hoad002. (PMID: 36873081)
Cureus. 2024 Jun 5;16(6):e61713. (PMID: 38975541)
Contributed Indexing: Keywords: PUFAs; antiphospholipid antibodies; fatty acid; infertility; recurrent spontaneous abortion
Substance Nomenclature: 0 (Fatty Acids)
0 (Fatty Acids, Omega-3)
0 (Fatty Acids, Omega-6)
0 (Antibodies, Antiphospholipid)
Entry Date(s): Date Created: 20260629 Date Completed: 20260629 Latest Revision: 20260813
Update Code: 20260814
PubMed Central ID: PMC13303191
DOI: 10.3389/fendo.2026.1866902
PMID: 42369069
Βάση Δεδομένων: MEDLINE
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  Data: Overlapping and distinct fatty acid dysregulation in infertility and recurrent spontaneous abortion.
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  Data: &lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Wei+S%22&quot;&gt;Wei S&lt;/searchLink&gt;; Department of Reproductive Medicine, The First Affiliated Hospital of Xi&#39;an Jiaotong University, Xi&#39;an, Shaanxi,&#160;China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Li+Y%22&quot;&gt;Li Y&lt;/searchLink&gt;; Department of Reproductive Medicine, The First Affiliated Hospital of Xi&#39;an Jiaotong University, Xi&#39;an, Shaanxi,&#160;China.; Assisted Reproduction Center, Northwest Women&#39;s and Children&#39;s Hospital, Xi&#39;an, Shaanxi,&#160;China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Luo+P%22&quot;&gt;Luo P&lt;/searchLink&gt;; Department of Reproductive Medicine, The First Affiliated Hospital of Xi&#39;an Jiaotong University, Xi&#39;an, Shaanxi,&#160;China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Yang+X%22&quot;&gt;Yang X&lt;/searchLink&gt;; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi&#39;an Jiaotong University, Xi&#39;an, Shaanxi,&#160;China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Zheng+PS%22&quot;&gt;Zheng PS&lt;/searchLink&gt;; Department of Reproductive Medicine, The First Affiliated Hospital of Xi&#39;an Jiaotong University, Xi&#39;an, Shaanxi,&#160;China.
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  Data: &lt;searchLink fieldCode=&quot;JN&quot; term=&quot;%22101555782%22&quot;&gt;Frontiers in endocrinology&lt;/searchLink&gt; [Front Endocrinol (Lausanne)] 2026 Jun 12; Vol. 17, pp. 1866902. &lt;i&gt;Date of Electronic Publication: &lt;/i&gt;2026 Jun 12 (&lt;i&gt;Print Publication: &lt;/i&gt;2026).
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  Data: &lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Abortion%2C+Habitual%22&quot;&gt;Abortion, Habitual*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Abortion%2C+Habitual+metabolism%22&quot;&gt;metabolism&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Abortion%2C+Habitual%22&quot;&gt;Abortion, Habitual*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Abortion%2C+Habitual+blood%22&quot;&gt;blood&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Fatty+Acids%22&quot;&gt;Fatty Acids*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Fatty+Acids+blood%22&quot;&gt;blood&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Fatty+Acids%22&quot;&gt;Fatty Acids*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Fatty+Acids+metabolism%22&quot;&gt;metabolism&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Infertility%2C+Female%22&quot;&gt;Infertility, Female*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Infertility%2C+Female+metabolism%22&quot;&gt;metabolism&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Infertility%2C+Female%22&quot;&gt;Infertility, Female*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Infertility%2C+Female+blood%22&quot;&gt;blood&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Fatty+Acids%2C+Omega-3%22&quot;&gt;Fatty Acids, Omega-3&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Fatty+Acids%2C+Omega-3+blood%22&quot;&gt;blood&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Fatty+Acids%2C+Omega-6%22&quot;&gt;Fatty Acids, Omega-6&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Fatty+Acids%2C+Omega-6+blood%22&quot;&gt;blood&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Antibodies%2C+Antiphospholipid%22&quot;&gt;Antibodies, Antiphospholipid&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Antibodies%2C+Antiphospholipid+blood%22&quot;&gt;blood&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Humans%22&quot;&gt;Humans&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Female%22&quot;&gt;Female&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Pregnancy%22&quot;&gt;Pregnancy&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Retrospective+Studies%22&quot;&gt;Retrospective Studies&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Adult%22&quot;&gt;Adult&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Case-Control+Studies%22&quot;&gt;Case-Control Studies&lt;/searchLink&gt;
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Introduction: Infertility and recurrent spontaneous abortion (RSA) are common reproductive disorders with rising incidence. Both fatty acid (FA) metabolism and antiphospholipid antibodies (aPL) are known to be associated with reproductive outcomes. However, their interaction and distinct roles in infertility versus RSA remain poorly understood.&lt;br /&gt;Methods: This retrospective study included 388 women (64 controls, 135 infertility cases, 189 RSA cases). FA profiles were measured from dried blood spots by gas chromatography. Candidate FAs were identified by FDR-corrected univariate analyses and refined by random forest. Core FAs were defined as the intersection of significant FAs and random forest-important variables. Associations between core FAs and aPL positivity were assessed by logistic regression. Mediation analysis used structural equation modeling.&lt;br /&gt;Results: An elevated omega-6/omega-3 ratio and lower DPAn3 were seen in both infertility and RSA. Infertility also showed a broader decline in omega-3-related FAs (omega-3, EPA, DHA; all P&#160;&amp;lt;&#160;0.05), while RSA featured higher behenic acid (P&#160;=&#160;0.023). The omega-6/omega-3 ratio was positively associated with aPL positivity in both groups (infertility: adjusted OR&#160;=&#160;3.51, 95% CI 2.24 - 5.91, P&#160;&amp;lt;&#160;0.001; RSA: OR&#160;=&#160;4.87, 95% CI 3.15 - 8.05, P&#160;&amp;lt;&#160;0.001); DPAn3 was inversely associated with aPL positivity in both groups (infertility: P&#160;&amp;lt;&#160;0.05; RSA: adjusted OR&#160;=&#160;0.33, 95% CI 0.18 - 0.53, P&#160;&amp;lt;&#160;0.001). In mediation analysis, aPL positivity partially mediated the relationship between the omega-6/omega-3 ratio (indirect effect 0.110, 30.7% mediated, P&#160;=&#160;0.045) and DPAn3 (indirect effect 0.080, 40.1% mediated, P&#160;=&#160;0.022) with RSA, but not with infertility.&lt;br /&gt;Discussion: Infertility and RSA exhibit overlapping yet distinct FA profiles. aPL positivity partially mediates the associations of the omega-6/omega-3 ratio and DPAn3 with RSA, but not with infertility. These findings demonstrate metabolic and immunological heterogeneity associated with different adverse reproductive outcomes.&lt;br /&gt; (Copyright &#169; 2026 Wei, Li, Luo, Yang and Zheng.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
– Name: Ref
  Label: References
  Group: RefInfo
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(PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2233915094%22&quot;&gt;33915094)&lt;/searchLink&gt;&lt;br /&gt;Mol Cell Biochem. 2015 Mar;401(1-2):11-9. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2225413343%22&quot;&gt;25413343)&lt;/searchLink&gt;&lt;br /&gt;Reprod Biol Endocrinol. 2022 Jul 25;20(1):107. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2235879714%22&quot;&gt;35879714)&lt;/searchLink&gt;&lt;br /&gt;J Nutr Biochem. 2021 Oct;96:108784. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2234062269%22&quot;&gt;34062269)&lt;/searchLink&gt;&lt;br /&gt;Hum Reprod Open. 2023 Mar 02;2023(1):hoad002. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2236873081%22&quot;&gt;36873081)&lt;/searchLink&gt;&lt;br /&gt;Cureus. 2024 Jun 5;16(6):e61713. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2238975541%22&quot;&gt;38975541)&lt;/searchLink&gt;
– Name: SubjectMinor
  Label: Contributed Indexing
  Group:
  Data: &lt;i&gt;Keywords: &lt;/i&gt;PUFAs; antiphospholipid antibodies; fatty acid; infertility; recurrent spontaneous abortion
– Name: NumberCAS
  Label: Substance Nomenclature
  Group: ID
  Data: 0 (Fatty Acids)&lt;br /&gt;0 (Fatty Acids, Omega-3)&lt;br /&gt;0 (Fatty Acids, Omega-6)&lt;br /&gt;0 (Antibodies, Antiphospholipid)
– Name: DateEntry
  Label: Entry Date(s)
  Group: Date
  Data: &lt;i&gt;Date Created: &lt;/i&gt;20260629 &lt;i&gt;Date Completed: &lt;/i&gt;20260629 &lt;i&gt;Latest Revision: &lt;/i&gt;20260813
– Name: DateUpdate
  Label: Update Code
  Group: Date
  Data: 20260814
– Name: PubmedCentralID
  Label: PubMed Central ID
  Group: ID
  Data: PMC13303191
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.3389/fendo.2026.1866902
– Name: AN
  Label: PMID
  Group: ID
  Data: 42369069
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42369069
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.3389/fendo.2026.1866902
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 1866902
    Subjects:
      – SubjectFull: Fatty Acids, Omega-3 blood
        Type: general
      – SubjectFull: Fatty Acids, Omega-6 blood
        Type: general
      – SubjectFull: Antibodies, Antiphospholipid blood
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Female
        Type: general
      – SubjectFull: Pregnancy
        Type: general
      – SubjectFull: Retrospective Studies
        Type: general
      – SubjectFull: Adult
        Type: general
      – SubjectFull: Case-Control Studies
        Type: general
      – SubjectFull: Abortion, Habitual metabolism
        Type: general
      – SubjectFull: Abortion, Habitual blood
        Type: general
      – SubjectFull: Fatty Acids blood
        Type: general
      – SubjectFull: Fatty Acids metabolism
        Type: general
      – SubjectFull: Infertility, Female metabolism
        Type: general
      – SubjectFull: Infertility, Female blood
        Type: general
    Titles:
      – TitleFull: Overlapping and distinct fatty acid dysregulation in infertility and recurrent spontaneous abortion.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Wei S
      – PersonEntity:
          Name:
            NameFull: Li Y
      – PersonEntity:
          Name:
            NameFull: Luo P
      – PersonEntity:
          Name:
            NameFull: Yang X
      – PersonEntity:
          Name:
            NameFull: Zheng PS
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 12
              M: 06
              Text: 2026 Jun 12
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-print
              Value: 1664-2392
          Numbering:
            – Type: volume
              Value: 17
          Titles:
            – TitleFull: Frontiers in endocrinology
              Type: main
ResultId 1