Maternal obesity alters feto-placental cytochrome P4501A1 activity

B. N. Dubois, P. O'Tierney-Ginn, J. Pearson, J. E. Friedman, Kent Thornburg, G. Cherala

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    Abstract

    Cytochrome P4501A1 (CYP1A1), an important drug metabolizing enzyme, is expressed in human placenta throughout gestation as well as in fetal liver. Obesity, a chronic inflammatory condition, is known to alter CYP enzyme expression in non-placental tissues. In the present study, we test the hypothesis that maternal obesity alters the distribution of CYP1A1 activity in feto-placental unit. Placentas were collected from non-obese (BMI <30) and obese (BMI > 30) women at term. Livers were collected from gestation day 130 fetuses of non-human primates fed either control diet or high-fat diet (HFD). Cytosol and microsomes were collected using differential centrifugation, and incubated with 7-ethoxyresorufin. The CYP1A1 specific activity (pmoles of resorufin formed/min/mg of protein) was measured at excitation/emission wavelength of 530/590 nm. Placentas of obese women had significantly reduced microsomal CYP1A1 activity compared to non-obese women (0.046 vs. 0.082; p <0.05); however no such effect was observed on cytosolic activity. Similarly, fetal liver from HFD fed mothers had significantly reduced microsomal CYP1A1 activity (0.44 ± 0.04 vs. 0.20 ± 0.10; p <0.05), with no significant difference in cytosolic CYP1A1 activity (control, 1.23 ± 0.20; HFD, 0.80 ± 0.40). Interestingly, multiple linear regression analyses of placental efficiency indicate cytosolic CYP1A1 activity is a main effect (5.67 ± 2.32 (β ± SEM); p = 0.022) along with BMI (-0.57 ± 0.26; p = 0.037), fetal gender (1.07 ± 0.26; p <0.001), and maternal age (0.07 ± 0.03; p = 0.011). In summary, while maternal obesity affects microsomal CYP1A1 activity alone, cytosolic activity along with maternal BMI is an important determinant of placental efficiency. Together, these data suggest that maternal lifestyle could have a significant impact on CYP1A1 activity, and hints at a possible role for CYP1A1 in feto-placental growth and thereby well-being of fetus.

    Original languageEnglish (US)
    Pages (from-to)1045-1051
    Number of pages7
    JournalPlacenta
    Volume33
    Issue number12
    DOIs
    Publication statusPublished - Dec 2012

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    Keywords

    • Cytochrome P4501A
    • Cytosol
    • Human placenta
    • Maternal obesity
    • Microsomes

    ASJC Scopus subject areas

    • Obstetrics and Gynecology
    • Reproductive Medicine
    • Developmental Biology

    Cite this

    Dubois, B. N., O'Tierney-Ginn, P., Pearson, J., Friedman, J. E., Thornburg, K., & Cherala, G. (2012). Maternal obesity alters feto-placental cytochrome P4501A1 activity. Placenta, 33(12), 1045-1051. https://doi.org/10.1016/j.placenta.2012.09.008