Journal Article Epublish 11 citations
PubMed: 39472874 DOI: 10.1186/s12884-024-06914-0
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.
BMC Pregnancy Childbirth 24(1):709
Authors: Aisha Nawaf Al Balawi, Noaf Abdullah N Alblwi, Riham Soliman, Ali H El-Far, Mervat G Hassan, Tarek El-Sewedy, Fuad Ameen, Nadia F Ismail, Alaa Elmetwalli
Affiliations
- Biology Department, University College of Haql, University of Tabuk, Tabuk, Saudi Arabia.
- Department of Nursing, Al Hadithah General Hospital, Al Qurayyat, Saudi Arabia.
- Tropical Medicine Department, Faculty of Medicine, Port Said University, Port Said, Egypt.
- Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, Mansoura, Egypt.
- Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, 646000, China.
- Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, Egypt.
- Department of Botany and Microbiology, Faculty of Science, Benha University, Benha, 13511, Egypt.
- Department of Applied Medical Chemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt.
- Department of Botany and Microbiology, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia.
- Health Information Management Program, Biochemistry, Faculty of Health Science Technology, Borg El Arab Technological University, Alexandria, Egypt.
- Department of Clinical Trial Research Unit and Drug Discovery, Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt.
- Microbiology Division, Higher Technological Institute of Applied Health Sciences, Egypt Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt.
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.
MeSH
Vitamin D, Pregnancy, Vitamins, Conflict, Psychological, Adenosine, Down-Regulation, Vitamin D Deficiency