TY - JOUR
T1 - Vitamin D sufficiency has a limited effect on placental structure and pathology
T2 - Placental phenotypes in the VDAART trial
AU - He, Mai
AU - Mirzakhani, Hooman
AU - Chen, Ling
AU - Wu, Robert
AU - Litonjua, Augusto A.
AU - Bacharier, Leonard
AU - Weiss, Scott T.
AU - Nelson, D. Michael
N1 - Funding Information:
We acknowledge the contribution of Denae Larson, RN, BSN, lead research nurse coordinator for the VDAART study, Baosheng Chen, PhD, and Mark Longtine, PhD, for their assistance in harvesting tissues from delivered placentas, and Marina Platik, AMP core lab for her work on histopathological processing of placental specimens. We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with the genomic analysis. The Center is partially supported by NCI Cancer Center Support Grant #P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA Grant# UL1TR002345 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH.
Funding Information:
Financial Support: The Vitamin D Antenatal Asthma Reduction Trial (VDAART, NIH grant #HL091528) to STW and AAL; L30HL129467-01, 2L30HL129467 and 1K01HL146977-01A1 from NIH NHLBI to H.M. The Foundation for Barnes-Jewish Hospital to D.M.N.Faculty development fund: Department of Pathology & Immunology, Washington University, to M.H.
Publisher Copyright:
© Endocrine Society 2020.
PY - 2020
Y1 - 2020
N2 - Vitamin D insufficiency during pregnancy is widespread. The effects of active vitamin D on the human placenta in vivo are unknown. We test the hypotheses that 25(OH)D sufficiency (arbitrarily defined as 25(OH)D ≥32 ng/mL) modulates placental structure and function in vivo in a population of women whose offspring are at risk for childhood asthma, and that placental pathology is more common in offspring that evolve asthma at age 3. Pregnant volunteers in the St. Louis, MO, cohort of the Vitamin D Antenatal Asthma Reduction Trial (VDAART, NIH grant #HL091528) participated in a nested case–control study and consented for the study of placentas after delivery. Maternal concentrations of 25(OH)D were measured at trial entry and in the third trimester. The histopathology of the placentas from women with sufficient 25(OH)D, versus insufficient, showed no clinically significant differences, but morphometry revealed villi of women with sufficient third-trimester 25(OH)D had a higher villous surface density. Notably, analyses of transcripts, extracted from formalin-fixed paraffin-embedded specimens, revealed higher expression of INTS9, vWF, MACC1, and ARMS2, and diminished expression of the CNTN5 genes in the insufficient group. A larger proportion of placentas showed chronic chorioamnionitis in offspring with versus without asthma at age 3. These findings suggest that maternal 25(OH)D insufficiency has a limited effect on human placental villous histopathology and morphometry, but attenuates a small number of placental gene expression profiles in this selected population. The association of placental chronic chorioamnionitis and offspring asthma is worthy of further study.
AB - Vitamin D insufficiency during pregnancy is widespread. The effects of active vitamin D on the human placenta in vivo are unknown. We test the hypotheses that 25(OH)D sufficiency (arbitrarily defined as 25(OH)D ≥32 ng/mL) modulates placental structure and function in vivo in a population of women whose offspring are at risk for childhood asthma, and that placental pathology is more common in offspring that evolve asthma at age 3. Pregnant volunteers in the St. Louis, MO, cohort of the Vitamin D Antenatal Asthma Reduction Trial (VDAART, NIH grant #HL091528) participated in a nested case–control study and consented for the study of placentas after delivery. Maternal concentrations of 25(OH)D were measured at trial entry and in the third trimester. The histopathology of the placentas from women with sufficient 25(OH)D, versus insufficient, showed no clinically significant differences, but morphometry revealed villi of women with sufficient third-trimester 25(OH)D had a higher villous surface density. Notably, analyses of transcripts, extracted from formalin-fixed paraffin-embedded specimens, revealed higher expression of INTS9, vWF, MACC1, and ARMS2, and diminished expression of the CNTN5 genes in the insufficient group. A larger proportion of placentas showed chronic chorioamnionitis in offspring with versus without asthma at age 3. These findings suggest that maternal 25(OH)D insufficiency has a limited effect on human placental villous histopathology and morphometry, but attenuates a small number of placental gene expression profiles in this selected population. The association of placental chronic chorioamnionitis and offspring asthma is worthy of further study.
KW - Asthma
KW - Gene expression
KW - Histopathology
KW - Morphometrics
KW - Placenta
KW - Vitamin D
UR - http://www.scopus.com/inward/record.url?scp=85085459368&partnerID=8YFLogxK
U2 - 10.1210/ENDOCR/BQAA057
DO - 10.1210/ENDOCR/BQAA057
M3 - Article
C2 - 32270179
AN - SCOPUS:85085459368
SN - 0013-7227
VL - 161
JO - Endocrinology (United States)
JF - Endocrinology (United States)
IS - 6
M1 - BQAA057
ER -