Embryonic lethality in mice due to carnitine transporter OCTN2 defect and placental carnitine deficiency

Shekhawat, Prem; Sonne, Srinivas; Matern, Dietrich; Ganapathy, Vadivel

doi:10.1016/j.placenta.2018.06.312

Cited by 5 publications

(2 citation statements)

References 21 publications

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“…Octn1 and Octn2 play a crucial role in the uptake of L-carnitine by the placenta (Grube et al, 2005;Wu et al, 2000). The defect in Octn2 was shown to induce embryonic lethality (Shekhawat et al, 2018). Although the role of placental Octn1 has been poorly understood, the decline in Octn1, whose substrates are similar to those of Octn2, might affect fetal growth.…”

Section: Discussionmentioning

confidence: 99%

Effects of single and repetitive valproic acid administration on the gene expression of placental transporters in pregnant rats: An analysis by gestational period

Jinno

Furugen

Kurosawa

et al. 2020

Reproductive Toxicology

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The use of valproic acid (VPA), an antiepileptic drug, during pregnancy, is known to increase various fetal risks. Since VPA has been known to inhibit histone deacetylases (HDACs); its administration could alter gene transcription levels. However, in vivo effects of VPA administration on placental transporters have not been fully elucidated. The purpose of the present study was to comprehensively evaluate the effects of single and repetitive VPA administration on the expression of placental transporters and analyze them by gestational day. We investigated 18 transporters ( 8ATP-binding cassette (ABC) and 10 solute carrier (SLC) transporters) in the placentas of pregnant rats that were orally administered 400 mg/kg/day VPA for one or four days, during mid-or late gestation. In the control rats, 4 ABC transporter genes (Abcb1a, 1b, Abcc2, Abcc4) were upregulated, 3 (Abcc3, Abcc5, Abcg2) downregulated through gestation, whereas 1 (Abcc1) was not changed.Regarding SLC transporters, 6 genes (Slc7a5, Slc16a3, Slc22a3, Slc22a4, Slco2b1, Slco4a1) were increased, 1 (Slc29a1) decreased through gestation, whereas 3 (Slc7a8, Slc22a5, Slco2a1) showed no significant change. Single VPA administration altered the expression of 9 transporters and repetitive administration, 13 transporters. In particular, VPA remarkably decreased Abcc4 and Slc22a4 in late gestation and increased Abcc5 during mid-gestation. Our findings indicated that VPA administration changed transporter expression levels in rat placenta, and suggested that sensitivity to VPA differs across gestational stages.

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Section: Discussionmentioning

confidence: 99%

Effects of single and repetitive valproic acid administration on the gene expression of placental transporters in pregnant rats: An analysis by gestational period

Jinno

Furugen

Kurosawa

et al. 2020

Reproductive Toxicology

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“…10 Defects in the OCTN2 transporter were shown to be associated with maternal complications in pregnancy and to have severe impact on reproductive capacity in OCTN2 knock-out mice, thereby confirming placental uptake of carnitine is pivotal for fetal organism. 11 The physiological role of OCTN1 is not yet completely understood 5 , even though the transporter is believed to be highly specific for ergothioneine, a natural compound acting as intracellular antioxidant. 12 In several non-placental tissues, OCTN1 has been recently revealed as an important protective component against oxidative stress 5,13 and shown to ensure anti-inflammatory effect.…”

Section: Introductionmentioning

confidence: 99%

Effect of inflammatory environment on the gene expression of OCTN1 (SLC22A4) and OCTN2 (SLC22A5) transporters in human trophoblast cell lines BeWo, HTR-8/SVneo and placental villous explants

Dudicova

Kacerovský

Čečková

2023

Preprint

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Inflammation accompany pregnancy for physiological reasons but can be also involved in pathological process with deleterious effect on placental function and fetal development. Transmembrane exchange of essential and waste substances in the placenta is one of the most important placental roles. This study focusses on two solute carrier transporters, OCTN1 (SLC22A4) and OCTN2 (SLC22A5), with OCTN2 playing a role in the placental uptake of L-carnitine and OCTN1 generally believed to ensure cell protection against oxidative stress. We employed two cellular models and ex vivo cultured human placental villous explants to address possible changes in the expression of placental OCTN1/2 upon inflammatory environment. Our data reveal the upregulation of OCTN1/ SLC22A4 in HTR-8/SVneo treated with TNF-α and IFN-γ. LPS was able to enhance OCTN1 expression in explants and IFN γ increased expression of OCTN1 in BeWo cells. OCTN2/ SLC22A5 expression was upregulated upon exposition of IFN-γ in HTR-8/SVneo cells but decreased following treatment of BeWo cells with TNF-α. TNF-α and also LPS further decreased expression of OCTN2 in ex vivo explants. In conclusion, our data show for the first time that the gene expression of OCTN1 as well as OCTN2 can be affected by inflammatory environment in human placenta.

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Contributions of Drug Transporters to Blood-Placental Barrier

Liu

2019

Advances in Experimental Medicine and Biology

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Embryonic lethality in mice due to carnitine transporter OCTN2 defect and placental carnitine deficiency

Cited by 5 publications

References 21 publications

Effects of single and repetitive valproic acid administration on the gene expression of placental transporters in pregnant rats: An analysis by gestational period

Effects of single and repetitive valproic acid administration on the gene expression of placental transporters in pregnant rats: An analysis by gestational period

Effect of inflammatory environment on the gene expression of OCTN1 (SLC22A4) and OCTN2 (SLC22A5) transporters in human trophoblast cell lines BeWo, HTR-8/SVneo and placental villous explants

Contributions of Drug Transporters to Blood-Placental Barrier

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