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

  • Molecular Toxicology
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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.

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Data availability statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Abbreviations

LPS:

Lipopolysaccharide

IUGR:

Intrauterine growth restriction

MEST:

Mesoderm specific transcript

GD:

Gestational day

CCND1:

Cyclin D1

PCNA:

Proliferating cell nuclear antigen

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Funding

This study was supported by the National Natural Science Foundation of China (82173559 and 31902225), Key Research and Development Projects of Anhui Province (202104j07020035), Top Talent Funding Project of Anhui Province in Colleges and Universities (gxbjZD2022011), Natural Science Foundation of Anhui Province (2208085MH205) and Promotion project of basic and clinical collaborative research from Anhui Medical University (2020xkjT038 and 2021xkjT022).

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Author notes

  1. Pei-Ying Jiang, Shuai Lin, and Jie-Ru Liu have contributed equally to this work.

Authors and Affiliations

  1. School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China

    Pei-Ying Jiang, Shuai Lin, Jie-Ru Liu, Yan Liu, Li-Ming Zheng, Qiang Hong & Yuan-Hua Chen

  2. Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Anhui Medical University, Hefei, 230601, China

    Yi-Jun Fan

  3. Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University, Hefei, 230032, China

    De-Xiang Xu & Yuan-Hua Chen

  4. Department of Toxicology, Anhui Medical University, Hefei, 230032, China

    De-Xiang Xu

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  1. Pei-Ying Jiang
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Contributions

Conceptualization: YHC; investigation: PYJ, SL, JRL, YL, LMZ, QH, YJF; data curation and formal analysis: PYJ, SL; funding acquisition: YHC, SL, LMZ, YJF; supervision: YHC; writing-original draft preparation: YHC; writing-review and editing: YHC, DXX.

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Correspondence to Yuan-Hua Chen.

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Jiang, PY., Lin, S., Liu, JR. et al. Paternal lipopolysaccharide exposure induced intrauterine growth restriction via the inactivation of placental MEST/PI3K/AKT pathway in mice. Arch Toxicol 97, 2929–2941 (2023). https://doi.org/10.1007/s00204-023-03584-3

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