Assessing Metabolic and Reproductive Consequences of Prenatal Paracetamol Exposure in Female CD1 Mice

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dc.authorid0000-0003-1496-1091
dc.authorid0000-0003-3082-1582
dc.authorid0000-0003-0764-7694
dc.authorid0000-0002-4530-701X
dc.authorid0000-0002-9702-4214
dc.authorid0000-0002-4890-299X
dc.contributor.authorEntezari, Bita
dc.contributor.authorBozdağ, Deniz
dc.contributor.authorİnce-Ergüç, Elif
dc.contributor.authorBuhur, Aylin
dc.contributor.authorTomruk, Cansın Şirin
dc.contributor.authorSabuncuoğlu, Suna
dc.contributor.authorYavaşoğlu, Altuğ
dc.contributor.authorGürer, Orhan Hande
dc.date.accessioned2026-08-14T07:26:10Z
dc.date.available2026-08-14T07:26:10Z
dc.date.issued2026
dc.departmentFakülteler, Diş Hekimliği Fakültesi, Temel Bilimler Bölümü
dc.description.abstractParacetamol is a widely used analgesic during pregnancy; however, emerging evidence suggests it may act as an endocrine/ metabolism disrupting compound. Using an F1 female CD1 mouse model, this study scrutinized the long-term metabolic and reproductive consequences linked to intrauterine paracetamol exposure. Pregnant dams were administered paracetamol at three dose levels (Cmax/10, Cmax, and Cmax×10) during a critical window of organogenesis (gestational days 7.5–16.5). Offspring were monitored until 17weeks of age to assess growth, glucose homeostasis, lipidomic profiles, and ovarian histology. Prenatal exposure did not significantly affect total body weight but induced a dose-dependent increase in peritoneal adipose tissue mass, particularly in the Cmax×10 group. Metabolic assessments revealed impaired glucose tolerance in the Cmax/10 group and increased insulin sensitivity across all dose groups. Adipose tissue gene expression analysis demonstrated upregulation of adipogenic markers (Pparγ, Lpl, Fasn), while untargeted lipidomics revealed consistent dysregulation of lipid species, including lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs), sphingomyelins (SMs), and triacylglycerols (TGs), indicating altered lipid storage and inflammatory signaling. Histological evaluation showed a marked reduction in total follicle number and increased follicular atresia following paracetamol exposure. Degenerative changes in oocytes and granulosa cells were observed, and multi-oocyte follicles (MOFs) were detected exclusively in the Cmax/10. Collectively, these findings demonstrate that intrauterine paracetamol exposure induces persistent developmental reprogramming in female offspring, characterized by visceral adiposity, disrupted lipid homeostasis, and depletion of the ovarian reserve. Notably, several endpoints exhibited non-monotonic dose–response relationships, underscoring the sensitivity of developing systems to even subtherapeutic paracetamol exposure.
dc.identifier.citationEntezari, B., Bozdag, D., Ince-Erguc, E., Buhur, A., Tomruk, C. S., Sabuncuoglu, S., Yavasoglu, A., & Gurer-Orhan, H. (2026). Assessing metabolic and reproductive consequences of prenatal paracetamol exposure in female CD1 mice. Journal of Applied Toxicology. Advance online publication.
dc.identifier.doi10.1002/jat.70367
dc.identifier.issn0260-437X
dc.identifier.pmid42535769
dc.identifier.urihttps://hdl.handle.net/20.500.12941/444
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakPubMed
dc.institutionauthorBuhur, Aylin
dc.language.isoen
dc.publisherWiley
dc.relation.ispartofJournal of Applied Toxicology
dc.relation.publicationcategoryMakale - Ulusal Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectCD1 Female Mice
dc.subjectIn Vivo
dc.subjectMetabolism
dc.subjectParacetamol
dc.subjectPrenatal Exposure
dc.subjectReproduction
dc.titleAssessing Metabolic and Reproductive Consequences of Prenatal Paracetamol Exposure in Female CD1 Mice
dc.typeArticle

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