Paternal lipopolysaccharide exposure induced intrauterine growth restriction via the inactivation of placental MEST/PI3K/AKT pathway in mice

Abstract Maternal lipopolysaccharide (LPS) exposure during pregnancy has been related to IUGR. Here, we explored whether paternal LPS exposure before mating impaired fetal development. All male mice except controls were intraperitoneally injected with LPS every other day for a total of five injections. The next day after the last LPS, male mice were mated with untreated female mice. Interestingly, fetal weight and crown-rump length were reduced, while the incidence of IUGR was increased in paternal LPS exposure group. Additionally, paternal LPS exposure leaded to poor placental development through causing cell proliferation inhibition and apoptosis. Additional experiment demonstrated that the inactivation of placental PI3K/AKT pathway might be involved in paternal LPS-induced cell proliferation inhibition and apoptosis of trophoblast cells. Furthermore, the mRNA and protein levels of mesoderm specific transcript (MEST), a maternally imprinted gene with paternal expression, were significantly decreased in mouse placentas from paternal LPS exposure. Further analysis showed that paternal LPS exposure caused the inactivation of placental PI3K/AKT pathway and then cell proliferation inhibition and apoptosis might be via down-regulating placental MEST. Overall, our results provide evidence that paternal LPS exposure causes poor placental development and subsequently IUGR may be via down-regulating MEST/PI3K/AKT pathway, and then inducing cell proliferation inhibition and apoptosis in placentas..

Medienart:

Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:97

Enthalten in:

Archives of toxicology - 97(2023), 11 vom: 21. Aug., Seite 2929-2941

Sprache:

Englisch

Beteiligte Personen:

Jiang, Pei-Ying [VerfasserIn]
Lin, Shuai [VerfasserIn]
Liu, Jie-Ru [VerfasserIn]
Liu, Yan [VerfasserIn]
Zheng, Li-Ming [VerfasserIn]
Hong, Qiang [VerfasserIn]
Fan, Yi-Jun [VerfasserIn]
Xu, De-Xiang [VerfasserIn]
Chen, Yuan-Hua [VerfasserIn]

Links:

Volltext [lizenzpflichtig]

Themen:

Cell proliferation
Intrauterine growth restriction
Mesoderm specific transcript
Mice
PI3K/AKT pathway
Paternal lipopolysaccharide

Anmerkungen:

© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

doi:

10.1007/s00204-023-03584-3

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC2145560629