Overlapping between CYP3A4 and CYP3A7 expression in the fetal human liver during development

Abstract

Objective: The cytochrome P450 (CYP450) superfamily is implicated in important life processes, including metabolism of many molecules. CYP3A account for the largest portion of CYP450 proteins in human, including CYP3A4, CYP3A5 and CYP3A7. The purpose of this study was to investigate the immunohistochemical expression of CYP3A4 and CYP3A7 in human liver at different post-conceptional (PC) ages. Methods: Human liver samples from 30 fetuses and newborns were, clustered according with the PC age, routinely processed for immunohistochemical analysis of CYP3A4 and CYP3A7. Results: CYP3A4 was positive in all but two cases, CYP3A7 was positive in all but one case, which was negative also for CYP3A4. Conclusions: Our data on immunohistochemical detection of CYP3A4 and CYP3A7 during development show that CYP3A4 expression is not restricted to the post-natal age, being the immunostaining for both CYP3A4 and CYP3A7 identical after 25 weeks of PC age, thus the relationship between these CYP450 isoforms should be considered much more complex than previous thought. A high interindividual variability was observed among subjects at all gestational age. The variable CYP3A expression suggests the existence of a marked interindividual variability in drug metabolism during the intrauterine life and in perinatal period.

The Risk of Congenital Heart Anomalies Following Prenatal Exposure to Serotonin Reuptake Inhibitors—Is Pharmacogenetics the Key?

“…Genetic polymorphisms of CYP3A4 contribute to a minor extent to drug pharmacokinetics and clinical therapy, including that of SRIs [66]. However, more recent evidence suggests high phenotypic inter-individual variability in foetal expression of CYP3A4 and CYP3A7, and that gestational age is not the most important covariate [67]. Foetal SNP CYP3A7*1E has been clinically demonstrated to reduce the efficacy of betamethasone in stimulating foetal lung maturity following maternal antenatal administration, although the exact mechanism remains unknown [68].…”

Immunohistochemical markers of CYP3A4 and CYP3A7: a new tool towards personalized pharmacotherapy of hepatocellular carcinoma

“… 16 However, CYP3A4 as well as CYP3A7 immunohistochemical positivity has been recently detected in foetal livers. 26 It is conceivable that the reported changes in the expression of CYP3A7 (up-regulation) and CYP3A4 (down-regulation) occurring after birth, as well as the restriction of CYP3A7 expression just in the prenatal life, 16 might not be as solid as previously established. In fact, the immunohistochemical patterns of CYP3A4 and CYP3A7 during development showed that the relationships between CYP3A4 and CYP3A7 are more complex then previously thought.…”

“…In fact, the immunohistochemical patterns of CYP3A4 and CYP3A7 during development showed that the relationships between CYP3A4 and CYP3A7 are more complex then previously thought. 26 The analysis of CYP genes in end-stage livers compared with normal donor liver showed that the expression of CYP3A4, CYP3A5 and CYP3A7 was decreased in HCC. 27 Immunohistochemical CYP3A4 positivity was previously reported in HCC, hepatocellular adenomas (HCA) and focal nodular hyperplasia (FNH), suggesting that the expression of CYP3A4 may change in HCA and HCC and indicating specific metabolic characterization in the subgroup of HCA and HCC.…”

“… 17 In a previous study, we showed the overlapping expression between CYP3A4 and CYP3A7 in the foetal human liver during development. 18 …”

Each niche has an actor: multiple stem cell niches in the preterm kidney

“…Classical morphology, associated to immune-histochemistry [ 43 ] and molecular biology [ 44 ] probably is not sufficient for reaching this goal. The triple I (interactive, intersectorial, interdisciplinary) approach is necessary for a better comprehension of nephrogenesis [ 45 ]. Which factors regulate exhaustion of stem/progenitor cells leading to cessation of nephrogenesis?…”