AUTHOR=Reginatto Mila W. , Pizarro Bartira M. , Antunes Roberto A. , Mancebo Ana C. A. , Hoffmann Luísa , Fernandes Pâmela , Areas Patrícia , Chiamolera Maria I. , Silva Rosane , Souza Maria do Carmo Borges de , Bloise Enrrico , Ortiga-Carvalho Tânia M. 

TITLE=Vitamin D Receptor TaqI Polymorphism Is Associated With Reduced Follicle Number in Women Utilizing Assisted Reproductive Technologies

JOURNAL=Frontiers in Endocrinology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2018.00252

DOI=10.3389/fendo.2018.00252

ISSN=1664-2392

ABSTRACT=<sec id="ST1"><title>Purpose</title><p>Calcitriol, or 1,25-hydroxycholecalciferol, is the active form of vitamin D. It binds and activates vitamin D receptor (VDR). Infertility and defective folliculogenesis have been observed in female <italic>vdr-</italic>knockout mice; however, whether <italic>VDR</italic> polymorphisms affect human ovarian responses to controlled ovarian stimulation (COS) remains unclear. We hypothesized that <italic>VDR</italic> polymorphisms are associated with infertility and COS responses. Thus, we evaluated the association between the <italic>TaqI, BsmI</italic>, and <italic>FokI VDR</italic> polymorphisms and ovarian responses in women undergoing COS.</p></sec><sec id="ST2"><title>Methods</title><p>In this study, we recruited a control group (<italic>n</italic> = 121) comprising volunteers with a history of natural conception and a second group of women undergoing COS (<italic>n</italic> = 70). <italic>TaqI, BsmI</italic>, and <italic>FokI</italic> genotyping was performed <italic>via</italic> restriction fragment length polymorphism analysis or TaqMan qPCR and Sanger sequencing. Intrafollicular 25(OH)D contents were measured in follicular fluid collected from COS patients during oocyte retrieval. Ovarian response parameters were obtained from patient medical records.</p></sec><sec id="ST3"><title>Results</title><p>There were no significant differences in the genotype frequencies of <italic>VDR</italic> polymorphisms (<italic>TaqI, BsmI</italic> and <italic>FokI)</italic> between the control and COS groups. However, the allele frequency of <italic>TaqI</italic> (C allele) was significantly lower in the COS group than in the control group (<italic>p</italic> = 0.02). Follicle number but not oocyte number was lower in patients with <italic>TaqI</italic> polymorphic (TC/CC) genotypes (<italic>p</italic> = 0.03). Importantly, the ratio between the number of follicles retrieved and intrafollicular estradiol concentrations was higher in patients with the TC/CC <italic>TaqI</italic> genotypes (<italic>p</italic> &lt; 0.02).</p></sec><sec id="ST4"><title>Conclusion</title><p>We identified an association between the <italic>VDR TaqI</italic> polymorphism and reduced follicle number in women undergoing COS, suggesting that <italic>VDR</italic> signaling affects the ovarian response to stimulation <italic>via</italic> unknown mechanisms.</p></sec>