Sterol Biosynthesis Inhibition in Pregnant Women Taking Prescription Medications

Thiago C. Genaro-Mattos, Korinne B. Klingelsmith, Luke B. Allen, Allison Anderson, Keri A. Tallman, Ned A. Porter, Zeljka Korade, Károly Mirnics

Research output: Contribution to journalArticlepeer-review

Abstract

Sterol biosynthesis is a critical homeostatic mechanism of the body. Sterol biosynthesis begins during early embryonic life and continues throughout life. Many commonly used medications, prescribed >200 million times in the United States annually, have a sterol biosynthesis inhibition side effect. Using our high-throughput LC-MS/MS method, we assessed the levels of post-lanosterol sterol intermediates (lanosterol, desmosterol, and 7-dehydrocholesterol (7-DHC)) and cholesterol in 1312 deidentified serum samples from pregnant women. 302 samples showing elevated 7-DHC were analyzed for the presence of 14 medications known to inhibit the 7-dehydrocholesterol reductase enzyme (DHCR7) and increase 7-DHC. Of the 302 samples showing 7-DHC elevation, 43 had detectable levels of prescription medications with a DHCR7-inhibiting side effect. Taking more than one 7-DHC-elevating medication in specific combinations (polypharmacy) might exacerbate the effect on 7-DHC levels in pregnant women, suggesting a potentially additive or synergistic effect. As 7-DHC and 7-DHC-derived oxysterols are toxic, and as DHCR7-inhibiting medications are considered teratogens, our findings raise potential concerns regarding the use of prescription medication with a DHCR7-inhibiting side effect during pregnancy. The use of prescription medications during pregnancy is sometimes unavoidable, but choosing a medication without a DHCR7-inhibiting side effect might lead to a heathier pregnancy and prevent putatively adverse outcomes for the developing offspring.

Original languageEnglish (US)
Pages (from-to)848-857
Number of pages10
JournalACS Pharmacology and Translational Science
Volume4
Issue number2
DOIs
StatePublished - Apr 9 2021

Keywords

  • 7-dehydrocholesterol
  • 7-dehydrocholesterol reductase enzyme
  • cholesterol
  • neurodevelopment
  • pregnancy

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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