Maternal Influenza A Virus Infection Restricts Fetal and Placental Growth and Adversely Affects the Fetal Thymic Transcriptome
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Influenza Virus Inoculum Preparation and Titration
2.3. Experimental Design and Sample Collection
2.4. Histopathology
2.5. Hemagglutination Inhibition (HI) Assay
2.6. Fetal Sex Determination
2.7. RNA Extraction
2.8. RNA Seq of E7.5 and E12.5 Placentae and E7.5 Thymus Pools
2.9. Pathway Analysis
2.10. Influenza A Virus Quantitative Real-Time Polymerase Chain Reaction
2.11. RT qPCR of Placentae and Thymus Pools
2.11.1. Primer Design
2.11.2. Target Gene Selection
2.11.3. Real-Time Polymerase Chain Reaction (RT-PCR) and RT-qPCR
2.12. Statistical Analysis
3. Results
3.1. Maternal Influenza Infection Induces Fetal Growth Restriction and Decreased Placental Weight
3.2. Placental Transcriptome and Histopathology in Influenza-Inoculated and Control Litters
3.3. Maternal Influenza Infection at E7.5 Is Associated with Transcript Downregulation of 957 Genes in the Fetal Thymus
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Target Gene | Accession Number | Primer Sequence |
---|---|---|
Reference genes | ||
Gpi1 | NM_008155 | F: CGAACACGGCCAAAGTGAAA |
R: AGCTGCTCGAAGTGGTCAAA | ||
Hprt | NM_013556 | F: AGTCCCAGCGTCGTGATTAG |
R: TCTCGAGCAAGTCTTTCAGTCC | ||
Taldo1 | NM_011528 | F: TTGGCTGCACAACGAAGACC |
R: ATTCGTTCCGTGAGCATCCG | ||
Thymus Canonical Pathway Genes | ||
Acta1 | NM_001272041 | F: CGCCAGCCTCTGAAACTAGA |
Calcium (Ca2+) signaling | R: ACGATGGATGGGAACACAGC | |
Cldn3 | NM_009902 | F: GCAAGGACTACGTCTGAGGG |
Tight junction | R: ACTGTGTGTCGTCTGTCACC | |
Mylpf | NM_016754 | F: ACCACGGTATGTTAAGGGCTG |
Hepatic fibrosis | R: CCTTCTTGGGTGCCATGTCTTA | |
Agt | NM_007428 | F: GTTGGCGCTGAAGGATACACA |
Neuroprotective | R: GACCCAGGTCAAGATGCAGAA | |
Thymus Immune Systems Genes | ||
Mal | NM_001171187 | F: GTGAGTTTGATGCAGCCTACC |
R: CCACTGCGGCGATGTTTTC | ||
Mal2 | NM_178920 | F: GGACGTACTCCGGAGCTTTC |
R: AGCTGTCACCGACACAAACA | ||
Placenta Genes | ||
Tmem150A | NM_144916.3 | F: TGAACAAGGGGGCCCTAAGA |
R: AGATGAGGGCCACCATAACAG | ||
Ppbp4 | NM_023785.3 | F: TGCTGATGTGGAAGTGATAGCC |
R: GAAGCAGCTGGTCAGTAACCT | ||
Ppbp8 | NM_023785.3 | F: ACAGCTGGAAAATCTGATGGCA |
R: CTCCTGGCCTGTACACATTCA | ||
A/California/07/2009(H1N1) | ||
Matrix | NC_026431.1 | F: AGATGAGTCTTCTAACCGAGGTCG |
R: TGCAAAGACACTTTCCAGTCTCTG | ||
Sexing genes | ||
Sry | NM_011564.1 | F: CTGGAGCTCTACAGTGATGA |
R: CAGTTACCAATCAACACATCAC | ||
Myog (control) | M95800.1 | F: TTACGTCCATCGTGGACAGCAT |
R: TGGGCTGGGTGTTAGTCTTAT |
Day of Inoculation | E3.5 | E7.5 | E12.5 | ||||||
---|---|---|---|---|---|---|---|---|---|
Control | Influenza | p | Control | Influenza | p | Control | Influenza | p | |
Number of litters | 3 | 5 | 8 | 9 | 5 | 5 | |||
Total number of fetuses | 26 | 43 | 59 | 59 | 36 | 44 | |||
Average number of fetuses per litter ± standard error of the mean (SEM) | 8.7 ± 0.7 | 8.6 ± 0.5 | 0.9456 | 7.38 ± 0.75 | 6.56 ± 0.78 | 0.4768 | 7.2 ± 0.6 | 8.8 ± 0.8 | 0.1622 |
Average fetal weight per litter (g) ± SEM | 1.16 ± 0.21 | 1.12 ± 0.07 | 0.8317 | 1.20 ± 0.02 | 1.03 ± 0.09 | 0.0674 | 1.25 ± 0.06 | 1.17 ± 0.04 | 0.2862 |
Average fetal weight (g) ± SEM | 1.12 ± 0.06 | 1.14 ± 0.01 | 0.7844 | 1.21 ± 0.02 | 1.02 ± 0.03 | <0.0001 | 1.23 ± 0.02 | 1.16 ± 0.01 | 0.0067 |
Average placental weight per litter (g) ± SEM | 0.13 ± 0.01 | 0.11 ± 0.002 | 0.0364 | 0.12 ± 0.01 | 0.10 ± 0.01 | 0.1432 | 0.11 ± 0.02 | 0.10 ± 0.01 | 0.4901 |
Average placental weight (g) ± SEM | 0.12 ± 0.005 | 0.11 ± 0.002 | 0.0008 | 0.121 ± 0.01 | 0.101 ± 0.003 | 0.0013 | 0.105 ± 0.01 | 0.098 ± 0.003 | 0.2740 |
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Van Campen, H.; Bishop, J.V.; Abrahams, V.M.; Bielefeldt-Ohmann, H.; Mathiason, C.K.; Bouma, G.J.; Winger, Q.A.; Mayo, C.E.; Bowen, R.A.; Hansen, T.R. Maternal Influenza A Virus Infection Restricts Fetal and Placental Growth and Adversely Affects the Fetal Thymic Transcriptome. Viruses 2020, 12, 1003. https://doi.org/10.3390/v12091003
Van Campen H, Bishop JV, Abrahams VM, Bielefeldt-Ohmann H, Mathiason CK, Bouma GJ, Winger QA, Mayo CE, Bowen RA, Hansen TR. Maternal Influenza A Virus Infection Restricts Fetal and Placental Growth and Adversely Affects the Fetal Thymic Transcriptome. Viruses. 2020; 12(9):1003. https://doi.org/10.3390/v12091003
Chicago/Turabian StyleVan Campen, Hana, Jeanette V. Bishop, Vikki M. Abrahams, Helle Bielefeldt-Ohmann, Candace K. Mathiason, Gerrit J. Bouma, Quinton A. Winger, Christie E. Mayo, Richard A. Bowen, and Thomas R. Hansen. 2020. "Maternal Influenza A Virus Infection Restricts Fetal and Placental Growth and Adversely Affects the Fetal Thymic Transcriptome" Viruses 12, no. 9: 1003. https://doi.org/10.3390/v12091003
APA StyleVan Campen, H., Bishop, J. V., Abrahams, V. M., Bielefeldt-Ohmann, H., Mathiason, C. K., Bouma, G. J., Winger, Q. A., Mayo, C. E., Bowen, R. A., & Hansen, T. R. (2020). Maternal Influenza A Virus Infection Restricts Fetal and Placental Growth and Adversely Affects the Fetal Thymic Transcriptome. Viruses, 12(9), 1003. https://doi.org/10.3390/v12091003