Placental CYP27B1 and CYP24A1 expression in human placental tissue and their association with maternal and neonatal calcitropic hormones.
BACKGROUND
Placental CYP27B1 may contribute to circulating maternal calcitriol concentrations across gestation, but determinants of CYP27B1 and CYP24A1 expression in term human placental tissue are not well established.


OBJECTIVE
We hypothesized that higher CYP27B1 protein expression would be associated with increased maternal calcitriol during gestation and that CYP27B1 expression would be impacted by substrate availability.


METHODS
This was a prospective, longitudinal study.


METHODS
The study was completed in an urban, prenatal clinic located in Rochester, New York.


METHODS
The study was undertaken in a cohort of 70 pregnant adolescents (≤18 y of age) and their term neonates.


METHODS
There was no intervention.


RESULTS
Protein and mRNA expressions of CYP27B1, CYP24A1, and vitamin D receptor were measured in term placental tissue and related to 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D, PTH, serum total calcium, IL-6, leptin, and osteoprotegerin measured in maternal serum at midgestation and delivery and in umbilical cord serum at birth.


RESULTS
Placental CYP27B1 protein expression was significantly positively associated with maternal 25(OH)D at both midgestation (n = 68, P = .009) and delivery (n=67, P = .006). Maternal serum 1,25-dihydroxyvitamin D concentrations at midgestation were positively correlated with term placental CYP27B1 mRNA expression (n = 49, P = .002). Significant positive associations were evident between placental CYP27B1 and CYP24A1 protein expression (P = .001, n = 70). Maternal PTH concentrations at midgestation or delivery did not significantly impact placental protein or transcript level of either enzyme. Variability in placental CYP27B1 protein expression was best captured by a model that included maternal midgestation 25(OH)D concentration, placental vitamin D receptor protein expression, and maternal midgestation IL-6 concentrations (P = .002, n = 60, R(2) = 0.22).


CONCLUSIONS
Higher maternal 25(OH)D during pregnancy was associated with significantly higher placental protein expression of CYP27B1 at term supportive of a link between substrate availability and placental production of calcitriol.
Division of Nutritional Sciences (K.O.O., S.L., C.C., T.K., B.V.Y.), Cornell University, Ithaca, New York 14853; The University of Rochester School of Medicine (R.A.Q., E.K.P., E.M.C.), Rochester, New York 14642.
Kimberly O
KO
O'Brien
Shuang
S
Li
Chang
C
Cao
Tera
T
Kent
Bridget V
BV
Young
Ruth Anne
RA
Queenan
Eva K
EK
Pressman
Elizabeth M
EM
Cooper
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D002118:Calcium / Q000378:metabolism*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry / Q000378:metabolism; D006728:Hormones / Q000097:blood*; D006801:Humans; D007231:Infant, Newborn / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008137:Longitudinal Studies; D010281:Parathyroid Hormone / Q000097:blood; D010920:Placenta / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D065668:Vitamin D3 24-Hydroxylase
D006728:Hormones; D015850:Interleukin-6; D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002118:Calcium