Investigation of a Paternal-Mediated Preeclampsia-Like Pregnancy Phenotype Mouse Model

Authors

  • Lauren K Burnette Brackenridge Fellow 2019, University Honors College, University of Pittsburgh, Pittsburgh, Pennsylvania
  • Mary Gemmel, PhD Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania
  • Marcia Gallaher, BS Magee-Womens Research Institute, Pittsburgh, Pennsylvania
  • Robert W Powers, PhD Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania

DOI:

https://doi.org/10.5195/pur.2021.15

Keywords:

preeclampsia, pregnancy, vascular function

Abstract

Preeclampsia, a pregnancy specific syndrome characterized by new onset hypertension and proteinuria, is a leading cause of maternal and neonatal morbidity and mortality. While no animal model perfectly mimics the human syndrome, breeding C1q-/- (male) to C57 (female) mice results in a preeclampsia-like pregnancy including pregnancy-specific hypertension, vascular dysfunction and altering placental phenotype. As the placental genotype is primarily paternally driven, lack of paternal C1q is likely driving this preeclampsia-like phenotype. However, more work is needed to investigate whether a lack of maternal C1q also contributes to this preeclampsia-like phenotype. The aim of this study was to investigate the pregnancy phenotype of genetic control (C1q-/- female bred to C57 male) mice. Blood pressure was monitored during pregnancy and vascular function assessed during late pregnancy (gestation day 17.5) in genetic control females. These data were compared to similar data obtained from control (C57 male bred to C57 female) and preeclampsia-like (C1q-/- male bred to C57 female) pregnant mice. Genetic control blood pressure and vascular function data were similar to that of the control pregnancy group, indicating no significant effect of maternal C1q deficiency on the “preeclampsia-like” pregnancy phenotype. As understanding preeclampsia and its effect on women’s health is critical, the work presented is important to confirm the C1q-/- x C57 mouse model as a useful model for studying this syndrome further.

Author Biographies

Mary Gemmel, PhD, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania

Postdoctoral Fellow, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.

Robert W Powers, PhD, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania

Associate Professor, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.

References

Aalkjaer C, Danielsen H, Johannesen P, Pedersen EB, Rasmussen A, and Mulvany MJ. Abnormal vascular function and morphology in pre-eclampsia: a study of isolated resistance vessels. Clin Sci (Lond) 69: 477-482, 1985. https://www.ncbi.nlm.nih.gov/pubmed/4042548

Agostinis C, Bulla R, Tripodo C, Gismondi A, Stabile H, Bossi F, Guarnotta C, Garlanda C, De Seta F, Spessotto P, Santoni A, Ghebrehiwet B, Girardi G, and Tedesco F. An alternative role of C1q in cell migration and tissue remodeling: contribution to trophoblast invasion and placental development. J Immunol 185: 4420-4429, 2010. https://www.ncbi.nlm.nih.gov/pubmed/20810993

American College of O, Gynecologists, and Task Force on Hypertension in P. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol 122: 1122-1131, 2013. https://www.ncbi.nlm.nih.gov/pubmed/24150027

Ananth CV, Keyes KM, and Wapner RJ. Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis. BMJ 347: f6564, 2013. https://www.ncbi.nlm.nih.gov/pubmed/24201165

Ashworth JR, Warren AY, Baker PN, and Johnson IR. Loss of endothelium-dependent relaxation in myometrial resistance arteries in pre-eclampsia. Br J Obstet Gynaecol 104: 1152-1158, 1997. https://www.ncbi.nlm.nih.gov/pubmed/9332993

Christians JK, Leavey K, and Cox BJ. Associations between imprinted gene expression in the placenta, human fetal growth and preeclampsia. Biol Lett 13: 2017. https://www.ncbi.nlm.nih.gov/pubmed/29187609

Colussi GL, Di Fabio A, Catena C, Chiuch A, and Sechi LA. Involvement of endothelium-dependent and -independent mechanisms in midazolam-induced vasodilation. Hypertens Res 34: 929-934, 2011. https://www.ncbi.nlm.nih.gov/pubmed/21614005

Demetriou C, Abu-Amero S, Thomas AC, Ishida M, Aggarwal R, Al-Olabi L, Leon LJ, Stafford JL, Syngelaki A, Peebles D, Nicolaides KH, Regan L, Stanier P, and Moore GE. Paternally expressed, imprinted insulin-like growth factor-2 in chorionic villi correlates significantly with birth weight. PLoS One 9: e85454, 2014. https://www.ncbi.nlm.nih.gov/pubmed/24454871

English FA, Kenny LC, and McCarthy FP. Risk factors and effective management of preeclampsia. Integr Blood Press Control 8: 7-12, 2015. https://www.ncbi.nlm.nih.gov/pubmed/25767405

Feng M, Whitesall S, Zhang Y, Beibel M, D'Alecy L, and DiPetrillo K. Validation of volume-pressure recording tail-cuff blood pressure measurements. Am J Hypertens 21: 1288-1291, 2008. https://www.ncbi.nlm.nih.gov/pubmed/18846043

Garrett N, Pombo J, Umpierrez M, Clark JE, Simmons M, and Girardi G. Pravastatin therapy during preeclampsia prevents long-term adverse health effects in mice. JCI Insight 3: 2018. https://www.ncbi.nlm.nih.gov/pubmed/29669946

Iacobaeus C, Andolf E, Thorsell M, Bremme K, Jorneskog G, Ostlund E, and Kahan T. Longitudinal study of vascular structure and function during normal pregnancy. Ultrasound Obstet Gynecol 49: 46-53, 2017. https://www.ncbi.nlm.nih.gov/pubmed/27731532

Khalil A, Hardman L, and P OB. The role of arginine, homoarginine and nitric oxide in pregnancy. Amino Acids 47: 1715-1727, 2015. https://www.ncbi.nlm.nih.gov/pubmed/26092522

Khong TY, De Wolf F, Robertson WB, and Brosens I. Inadequate maternal vascular response to placentation in pregnancies complicated by pre-eclampsia and by small-for-gestational age infants. Br J Obstet Gynaecol 93: 1049-1059, 1986. https://www.ncbi.nlm.nih.gov/pubmed/3790464

McCarthy AL, Woolfson RG, Raju SK, and Poston L. Abnormal endothelial cell function of resistance arteries from women with preeclampsia. Am J Obstet Gynecol 168: 1323-1330, 1993. https://www.ncbi.nlm.nih.gov/pubmed/7682754

Powers RW, Gandley RE, Lykins DL, and Roberts JM. Moderate hyperhomocysteinemia decreases endothelial-dependent vasorelaxation in pregnant but not nonpregnant mice. Hypertension 44: 327-333, 2004. https://www.ncbi.nlm.nih.gov/pubmed/15249551

Rinkenberger J, and Werb Z. The labyrinthine placenta. Nat Genet 25: 248-250, 2000. https://www.ncbi.nlm.nih.gov/pubmed/10888863

Roberts JM. Endothelial dysfunction in preeclampsia. Semin Reprod Endocrinol 16: 5-15, 1998. https://www.ncbi.nlm.nih.gov/pubmed/9654603

Roberts JM, and Bell MJ. If we know so much about preeclampsia, why haven't we cured the disease? J Reprod Immunol 99: 1-9, 2013. https://www.ncbi.nlm.nih.gov/pubmed/23890710

Roberts JM, and Cooper DW. Pathogenesis and genetics of pre-eclampsia. Lancet 357: 53-56, 2001. https://www.ncbi.nlm.nih.gov/pubmed/11197372

Singh J, Ahmed A, and Girardi G. Role of complement component C1q in the onset of preeclampsia in mice. Hypertension 58: 716-724, 2011. https://www.ncbi.nlm.nih.gov/pubmed/21859968

Sutton EF, Gemmel M, Brands J, Gallaher MJ, and Powers RW. Paternal deficiency of complement component C1q leads to a preeclampsia-like pregnancy in wild-type female mice and vascular adaptations postpartum. Am J Physiol Regul Integr Comp Physiol 318: R1047-R1057, 2020. https://www.ncbi.nlm.nih.gov/pubmed/32374620

Sutton EF, Gemmel M, and Powers RW. Nitric oxide signaling in pregnancy and preeclampsia. Nitric Oxide 95: 55-62, 2020. https://www.ncbi.nlm.nih.gov/pubmed/31852621

Wennmalm A. Endothelial nitric oxide and cardiovascular disease. J Intern Med 235: 317-327, 1994. https://www.ncbi.nlm.nih.gov/pubmed/8151263

Zhang P. Phenotypic Switch of Endovascular Trophoblasts in Decidual Vasculopathy with Implication for Preeclampsia and Other Pregnancy Complications. Fetal Pediatr Pathol 1-20, 2020. https://www.ncbi.nlm.nih.gov/pubmed/32068473

Cover image of issue 1. View of Cathedral of Learning against a night sky, with PUR logo. Light appears on on the 36th floor.

Downloads

Published

2021-07-21

How to Cite

Burnette, L., Gemmel, M., Gallaher, M., & Powers, R. (2021). Investigation of a Paternal-Mediated Preeclampsia-Like Pregnancy Phenotype Mouse Model. Pittsburgh Undergraduate Review, 1(1). https://doi.org/10.5195/pur.2021.15

Issue

Vol. 1 No. 1 (2021): Pittsburgh Undergraduate Review

Section

Research

License

Authors who publish with this journal agree to the following terms:

  1. The Author retains copyright in the Work, where the term “Work” shall include all digital objects that may result in subsequent electronic publication or distribution.
  2. Upon acceptance of the Work, the author shall grant to the Publisher the right of first publication of the Work.
  3. The Author shall grant to the Publisher and its agents the nonexclusive perpetual right and license to publish, archive, and make accessible the Work in whole or in part in all forms of media now or hereafter known under a Creative Commons Attribution 4.0 International License or its equivalent, which, for the avoidance of doubt, allows others to copy, distribute, and transmit the Work under the following conditions:
    1. Attribution—other users must attribute the Work in the manner specified by the author as indicated on the journal Web site;
    with the understanding that the above condition can be waived with permission from the Author and that where the Work or any of its elements is in the public domain under applicable law, that status is in no way affected by the license.
  4. The Author is able to enter into separate, additional contractual arrangements for the nonexclusive distribution of the journal's published version of the Work (e.g., post it to an institutional repository or publish it in a book), as long as there is provided in the document an acknowledgement of its initial publication in this journal.
  5. Authors are permitted and encouraged to post online a prepublication manuscript (but not the Publisher’s final formatted PDF version of the Work) in institutional repositories or on their Websites prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work. Any such posting made before acceptance and publication of the Work shall be updated upon publication to include a reference to the Publisher-assigned DOI (Digital Object Identifier) and a link to the online abstract for the final published Work in the Journal.
  6. Upon Publisher’s request, the Author agrees to furnish promptly to Publisher, at the Author’s own expense, written evidence of the permissions, licenses, and consents for use of third-party material included within the Work, except as determined by Publisher to be covered by the principles of Fair Use.
  7. The Author represents and warrants that:
    1. the Work is the Author’s original work;
    2. the Author has not transferred, and will not transfer, exclusive rights in the Work to any third party;
    3. the Work is not pending review or under consideration by another publisher;
    4. the Work has not previously been published;
    5. the Work contains no misrepresentation or infringement of the Work or property of other authors or third parties; and
    6. the Work contains no libel, invasion of privacy, or other unlawful matter.
  8. The Author agrees to indemnify and hold Publisher harmless from Author’s breach of the representations and warranties contained in Paragraph 6 above, as well as any claim or proceeding relating to Publisher’s use and publication of any content contained in the Work, including third-party content.
  9. The Author agrees to digitally sign the Publisher’s final formatted PDF version of the Work.