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In vitro fertilization (IVF) is a widely used assisted reproductive technology for individuals with infertility that may cause placental maldevelopment, which is harmful to the future health of the offspring. In this study, using a mouse model, we not only revealed changes in the placenta caused by IVF at embryonic day 18.5 (E18.5), but also attempted to identify factors that correlate with IVF‐induced abnormal placental development. Our results demonstrate that IVF‐induced placental maldevelopment is associated with hypermethylation of the imprinting control region of the H19 imprinted maternally expressed transcript (H19). IVF, by inducing overexpression of DNA methyltransferase 3β, downregulated H19 and the derived miR675, resulting in the activation of insulin‐like growth factor signaling and its downstream phosphoinositide 3‐kinase/AKT/mammalian target of rapamycin pathway. Therefore, we provided the first evidence of the molecular signaling pathways that link imprint genes, protein encoding genes, long noncoding RNAs, and microRNAs. This may provide new insights to inform the development of improved operational techniques for IVF and life‐long health of the offspring.

The vaginal administration route suffers from relatively low absorption efficiency, which may hinder the identification of the toxicokinetics of curdione in pregnant women. A sensitive analytical method for determining the plasma concentration of curdione was developed and applied in the determination of curdione in pregnant Sprague-Dawley rats as a simulated model. Glimepiride was used as an internal standard and chromatographic separation was achieved on a Capcell Pak C18 MGIII column. A gradient elution profile with 0.5% formic acid (A)-0.5% formic acid-acetonitrile (B) was selected as mobile phase. The selected reaction monitoring mode was used for quantification based on the target fragment ions m/z 237.2 to m/z 135.1 for curdione and m/z 491.3 to m/z 352.1 for the glimepiride. The standard curve was linear over the range of 0.5-500 ng/mL for curdione in rat plasma and yielded a consistent peak pattern, even at the lower limit of quantitation of 0.5 ng/mL. The retention times of curdione and IS were 6.55 and 6.59 min, respectively. The mean recovery of curdione in rat plasma was 95.5-101.1%. The intra-day and inter-day precisions were between 2.35 and 9.08%. This LC-MS/MS method provides a simple and sensitive means for determining the plasma concentration.