Vitamin D deficiency and female infertility: A mechanism review examining the role of vitamin D in ovulatory dysfunction as a symptom of polycystic ovary syndrome. (June 2022)

• Record Type: Journal Article
• Authors: Berry, Sinéad; Seidler, Karin; Neil, James
• Is Part Of: Journal of reproductive immunology. Volume 151(2022)
• Publication Date: 2022-06
• Subjects: 1, 25OH2D3 1, 25-dihydroxyvitamin D/calcitriol/VD3 -- 25OHD Calcidiol -- 3β-HSD 3β-Hydroxysteroid Dehydrogenase -- 7-DHC 7-dehydrocholesterol -- A4 Androstenedione -- AGE Advanced Glycation End Product -- AMH Anti-Mullerian Hormone -- AMHR Anti-Mullerian Hormone Receptor -- AMPK AMP‐activated Protein Kinase -- cAMP Cyclic Adenosine Monophosphate -- CAT Catalase -- CRP C-Reactive Protein -- DC Dendritic Cells -- DHEA Dehydroepiandrosterone -- DHEAS Dehydroepiandrosterone Sulphate -- E2 Oestradiol (oestrogen) -- EPO Evening Primrose Oil -- FAI Free Androgen Index -- FSH Follicle Stimulating Hormone -- FSHR Follicle Stimulating Hormone Receptor -- FT Free Testosterone -- GC Granulosa Cell -- GLO-1 Glyoxalase-1 -- GSH Glutathione -- hs-CRP High-Sensitivity C-Reactive Protein -- IOM Institute of Medicine -- IVF In vitro fertilisation -- LH Luteinizing Hormone -- LOX Lysyl Oxidase -- MDA Malondialdehyde -- MG Methylglyoxal -- mRNA Messenger Ribonucleic Acid -- NF-kB Nuclear Factor Kappa-B -- NK Natural Killer Cells -- NO Nitric Oxide -- NOS The National Osteoporosis Society -- P4 Progesterone -- PCOS Polycystic Ovary Syndrome -- RAGE Receptor for Advanced Glycation End-Products -- RCT Randomised Controlled Trial -- ROS Reactive Oxygen Species -- SHBG Sex Hormone Binding Globulin -- SOD Superoxide Dismutase -- sRAGE Soluble Receptor for Advanced Glycation End-Products -- StAR Steroidogenic Acute Regulatory Protein -- T Testosterone -- TAC Total Antioxidant Capacity -- TLR Toll-like Receptors -- Tregs Regulatory T cells -- TT Total Testosterone -- VD3 Vitamin D3 (calcitriol) -- VDR Vitamin D Receptor -- VEGF Vascular Endothelial Growth Factor -- WT Wild-Type; Vitamin D -- PCOS -- Infertility -- Anovulation -- Folliculogenesis -- Nutritional interventions; Reproduction -- Immunological aspects -- Periodicals; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Reproduction -- Periodicals; Reproduction -- Immunologie -- Périodiques; Immunologie -- Périodiques; Immunology; Reproduction -- Immunological aspects; Periodicals; Electronic journals; Electronic journals; 615.766
• DOI: 10.1016/j.jri.2022.103633
• Languages: English
• ISSNs: 0165-0378

Abstract

Abstract: Around one billion people worldwide are understood to have sub-optimal levels of vitamin D. Polycystic ovary syndrome (PCOS) is reportedly a primary reason for female infertility. The main objective of this research was to understand the mechanistic role of vitamin D in the pathogenesis of female infertility in PCOS, specifically in relation to ovarian follicle development. In addition, the impact of vitamin D deficiency on oxidative stress and hormone production central to folliculogenesis was explored. The efficacy of vitamin D supplementation as an intervention to ameliorate ovulatory dysfunction in individuals with PCOS was evaluated. The systematic search strategy included three stages of search with a critical appraisal of the accepted papers: 1) other review papers; 2) primary mechanistic animal, in vitro and human studies; 3) primary intervention studies. In total, 80 papers were examined in detail and results analysed and evaluated. Mechanistic evidence indicated an association between vitamin D deficiency and impaired ovulatory function. Sub-optimal vitamin D levels were implicated in disrupted reproductive hormone balance, including overproduction of anti-mullerian hormone (AMH); accumulation of pro-inflammatory Advanced Glycation End Products (AGEs) and formation of Reactive Oxygen Species (ROS) in ovarian tissue, leading to abnormal folliculogenesis. Human intervention studies demonstrated the capability of vitamin D supplementation for restoring sufficient serum calcidiol (25(OH)D) levels in deficient individuals. Furthermore, the anti-inflammatory benefit of vitamin D was illustrated in studies examining the impact on oxidative stress. Co-supplementation with calcium was shown to benefit follicle growth; oxidative stress reduced with calcium, omega-3 fatty acid or probiotic co-supplementation. Graphical Abstract: ga1 Highlights: Vitamin D plays a role in pathophysiological mechanisms of infertility in PCOS. Vitamin D deficiency is linked to dysregulation of hormones and folliculogenesis. Advanced Glycation End Products are implicated in anovulation in PCOS. A suitable reproductive environment may be supported by vitamin D sufficiency. Irregular follicle development may be reversed with vitamin D supplementation.