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Placental cell death patterns exhibit differences throughout gestation in two strains of laboratory mice

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Abstract

Cell death is an essential physiological process required for the proper development and function of the human placenta. Although the mouse is a commonly used animal model for development studies, little is known about the extent and distribution of cell death in the mouse placenta throughout development and its physiological relevance. In the present study, we report the results of a systematic and quantitative assessment of cell death patterns in the placentae of two strains of laboratory mice commonly used for developmental studies—ICR and C57Bl/6. TUNEL staining revealed that ICR and C57Bl/6 placentae exhibited similar cell death patterns to those reported in human placentae during pregnancy, with comparatively infrequent death observed during early gestation, which increased and became more organized towards term. Interestingly, when comparing strain differences, increased cell death was observed in almost all regions of the inbred C57Bl/6 placentae compared to the outbred ICR strain. Finally, since Bcl-2 ovarian killer (Bok) has been reported to be a key player in human placental cell death, we examined its expression in murine placentae throughout gestation. Bok protein expression was observed in all placental regions and increased towards term in both strains. The results of this study indicate that although strain-specific differences in placental cell death exist, the overall rates and patterns of cell death during murine placentation parallel those previously described in humans. Thus, the murine placenta is a useful model to investigate molecular pathways involved in cell death signaling during human placentation.

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Funding

This work was supported by research grants from the SickKids Foundation and NSERC (RGPIN-04497) to AJ and Canadian Institute of Health Research (MOP-89813) awarded to IC. During these studies, JD was funded by a Doctoral Research Award from the National Sciences and Engineering Research Council, JR was funded by CIHR DRA scholarship and Genesis foundation OGS program and IR was supported by LTRI-OSOTF program.

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  1. Jacqui Detmar

    Present address: MedAvail Technologies Inc., 6810 Meadowvale Town Centre Circle, Unit 18, Mississauga, ON, L5N 7T5, Canada

  2. Isidora Rovic and Jacqui Detmar contributed equally to this work.

Authors and Affiliations

  1. Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada

    Jacqui Detmar, Isidora Rovic, Jocelyn Ray, Isabella Caniggia & Andrea Jurisicova

  2. Institute of Medical Sciences, University of Toronto, Toronto, Canada

    Jacqui Detmar & Isabella Caniggia

  3. Department of Physiology, University of Toronto, Toronto, Canada

    Isidora Rovic, Jocelyn Ray, Isabella Caniggia & Andrea Jurisicova

  4. Department of Obstetrics and Gynecology, University of Toronto, Toronto, Canada

    Isabella Caniggia & Andrea Jurisicova

  5. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Room 6-1016-1AJ, 25 Orde Street, Toronto, ON, M5T 3H7, Canada

    Andrea Jurisicova

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  1. Jacqui Detmar
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Correspondence to Andrea Jurisicova.

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All mouse experiments were performed in accordance with the Canadian Council on Animal Care (CCAC) guidelines for Use of Animals in Research and Laboratory Animal Care under protocols approved by animal care committees at Mount Sinai Hospital or the Toronto Centre for Phenogenomics.

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Detmar, J., Rovic, I., Ray, J. et al. Placental cell death patterns exhibit differences throughout gestation in two strains of laboratory mice. Cell Tissue Res 378, 341–358 (2019). https://doi.org/10.1007/s00441-019-03055-1

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