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Comparative Proteomic and Phospho-proteomic Analysis of Mouse Placentas Generated via In Vivo and In Vitro Fertilization

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Abstract

Offspring conceived by assisted reproductive technologies (ART) have increased risk of suffering from gestational complications, and placental dysfunction is related with the adverse outcomes. Studies have revealed that abnormal or adaptive changes can occur in ART placentas, but the potential reasons are not fully understood. Hereby, we tried to use proteomics and phospho-proteomics to find the underlying mechanisms responsible for the changes of ART placentas. Liquid chromatography–tandem mass spectrometry was utilized to perform proteome and phospho-proteome detection on mouse placentas. The differential expressed proteins (DEPs) or phospho-proteins (DEPPs) were analyzed based on subcellular localization, functional classification, and enrichment. Western blot was used to verify the DEPs (Afadin, ZO-1, Ace2, Agt, Slc7a5, and Slc38a10) and measure mTOR signaling activities (mTOR, Rps6, and 4Ebp1). The data showed that 161 DEPs and 304 DEPPs were found in proteome and phospho-proteome, respectively. Multiple biological processes were enriched based on those DEPs and DEPPs, and renin–angiotensin system, cell junction, and PI3K-Akt pathway were investigated. By protein expression identification, two key proteins associated with renin–angiotensin system (Ace2 and Agt) were down-regulated, and the levels of Afadin and ZO-1 (related with cell junction) as well as Slc38a10 were increased in IVF placentas. In addition, mTOR downstream activities were increased as shown by p-Rps6 and p-4Ebp1 in IVF placentas. In conclusion, IVF leads to the changes of cell junction, renin–angiotensin system, amino acid transport, and increased mTOR signaling in mouse placentas, which may be associated with the altered structure and function of IVF placentas.

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Data Availability

The data in this study are not publicly available due to their containing information that could compromise the privacy of research participants. However, the data are available from the corresponding author X.W. (wangxh919@fmmu.edu.cn) on reasonable request.

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Acknowledgements

We thank all authors who were involved in this study. We also appreciate Dr. Lei Zhao for helping to edit the manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (82071717, 82101794) and Tangdu Hospital Platform Construction Program (2020XKPT003).

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  1. Jie Dong and Qian Xu contributed equally to this article.

Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Tangdu Hospital, Air Force Medical University, Xi’an, 710038, Shaanxi Province, China

    Jie Dong, Qian Xu, Shuqiang Chen, Hui Lei, Jingjing Wang, Song Yan, Chenxi Qian & Xiaohong Wang

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Contributions

J.D. was involved in study design, data acquisition and analysis, and manuscript writing. Q.X. participated in data collection and manuscript writing. S.C., H.L., and J.W. participated in experiment practices. S.Y. and C.Q. engaged in data analysis. X.W. participated in the study design and helped to edit the manuscript.

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Correspondence to Xiaohong Wang.

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Dong, J., Xu, Q., Chen, S. et al. Comparative Proteomic and Phospho-proteomic Analysis of Mouse Placentas Generated via In Vivo and In Vitro Fertilization. Reprod. Sci. 30, 1143–1156 (2023). https://doi.org/10.1007/s43032-022-01109-4

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