NDLI: Impact of Vitamin D deficiency on immunological and metabolic responses in women with recurrent pregnancy loss: focus on VDBP/HLA-G1/CTLA-4/ENTPD1/adenosine-fetal-maternal conflict crosstalk

Content Provider	Springer Nature : BioMed Central
Author	Al Balawi, Aisha Nawaf Alblwi, Noaf Abdullah N. Soliman, Riham El-Far, Ali H. Hassan, Mervat G. El-Sewedy, Tarek Ameen, Fuad Ismail, Nadia F. Elmetwalli, Alaa
Abstract	Background and aim Recurrent pregnancy loss (RPL), also known as recurrent implantation failure (RIF), is a distressing condition affecting women characterized by two or more consecutive miscarriages or the inability to carry a pregnancy beyond 20 weeks. Immunological factors and genetic variations, particularly in Vit D Binding Protein (VDBP), have gained attention as potential contributors to RPL. This study aimed to provide insight into the immunological, genetic, and metabolic networks underlying RPL, placing a particular emphasis on the interactions between VDBP, HLA-G1, CTLA-4, ENTPD1, and adenosine-fetal-maternal conflict crosstalk. Methods A retrospective study included 198 women with three or more consecutive spontaneous abortions. Exclusion criteria comprised uterine abnormalities, endocrine disorders, parental chromosomal abnormalities, infectious factors, autoimmune diseases, or connective tissue diseases. Immunological interplay was investigated in 162 female participants, divided into two groups based on their Vit D levels: normal Vit D-RPL and low Vit D-RPL. Various laboratory techniques were employed, including LC/MS/MS for Vit D measurement, ELISA for protein detection, flow cytometry for immune function analysis, and molecular docking for protein–ligand interaction assessment. Results General characteristics between groups were significant regarding Vit D and glucose levels. Low Vit D levels were associated with decreased NK cell activity and downregulation of HLA-G1 and HLA-G5 proteins, while CTLA-4 revealed upregulation. VDBP was significantly downregulated in the low Vit D group. Our findings highlight the intricate relationship between Vit D status and adenosine metabolism by the downregulation of SGLT1, and NT5E, key components of adenosine metabolism, suggests that Vit D deficiency may disrupt the regulation of adenosine levels, leading to an impaired reproductive outcome. HNF1β, a negative regulator of VDBP, was upregulated, while HNF1α, a positive regulator, was downregulated in low Vit D women after RPL. Molecular docking analysis revealed crucial residues involved in the interaction between Vit D and HNF1β. Conclusion Collectively, these findings underscore the importance of Vit D in modulating immune function and molecular pathways relevant to pregnancy maintenance, highlighting the need for further research to elucidate the mechanisms and potential therapeutic interventions for improving pregnancy outcomes in individuals with Vit D deficiency and RPL.
Related Links	https://bmcpregnancychildbirth.biomedcentral.com/counter/pdf/10.1186/s12884-024-06914-0.pdf
Ending Page	19
Page Count	19
Starting Page	1
File Format	HTM / HTML
ISSN	14712393
DOI	10.1186/s12884-024-06914-0
Journal	BMC Pregnancy and Childbirth
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2024-10-29
Access Restriction	Open
Subject Keyword	Reproductive Medicine Maternal and Child Health Gynecology Recurrent pregnancy loss Genetic variation Vitamin D-Binding protein CTLA-4 Antigen Fetal-maternal conflict
Content Type	Text
Resource Type	Article
Subject	Obstetrics and Gynecology
Journal Impact Factor	2.8/2023
5-Year Journal Impact Factor	3.4/2023

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