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The Effect of Maternal Obesity on Placental Cell-Free DNA Release in a Mouse Model

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Abstract

Background

The fetal fraction of cell-free DNA (cfDNA) in maternal plasma is decreased in obese women. The underlying mechanism is not well understood. The amount of cfDNA released from the placenta has not been directly examined in maternal obesity.

Objective

We sought to quantify release of cfDNA from the placenta and fetal membranes in maternal diet-induced obesity using explant cultures in an established mouse model.

Study Design

C57BL6/J females were fed either 60% high-fat diet or 10% fat-matched control diet for 14 weeks prepregnancy and throughout gestation. Placentas and fetal membranes were collected on e18 and randomly allocated to time 0-, 1-, or 6-hour culture times. The CfDNA was isolated from culture media, quantified, and normalized to tissue weight.

Results

Placentas from obese dams released significantly less cfDNA compared to those of lean dams at time 0 (45.8 ± 4.3 ng/mg vs 65.6 ± 7.9 ng/mg, P =.02). Absolute cfDNA levels increased with longer placental culture, with no significant differences between obese and lean dams at 1 and 6 hours. Membranes released significantly less cfDNA than did placentas at every time point.

Conclusions

Maternal obesity is associated with decreased release of cfDNA from the placenta compared to lean controls immediately after tissue harvest. This may provide an alternative explanation for the lower fetal fraction of cfDNA noted in maternal obesity.

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Author information

Author notes

  1. Andrea Edlow MD, MSc

    Present address: Vincent Center for Reproductive Biology and Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Tufts Medical Center, 800 Washington Street, Box 360, Boston, MA, 02111, USA

    Mohak Mhatre MD, Errol Norwitz MD, PhD, MBA, Sabrina Craigo MD & Andrea Edlow MD, MSc

  2. Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA

    Sharareh Adeli PhD, PharmD & Mark Phillippe MD, MHCM

  3. Tufts University School of Medicine, Boston, MA, USA

    Errol Norwitz MD, PhD, MBA, Sabrina Craigo MD & Andrea Edlow MD, MSc

  4. Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, USA

    Mark Phillippe MD, MHCM

  5. Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, MA, USA

    Andrea Edlow MD, MSc

Authors
  1. Mohak Mhatre MD
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  2. Sharareh Adeli PhD, PharmD
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  6. Andrea Edlow MD, MSc
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Corresponding author

Correspondence to Mohak Mhatre MD.

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Authors’ Note

Study was conducted at Tufts Medical Center, Massachusetts General Hospital.

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Mhatre, M., Adeli, S., Norwitz, E. et al. The Effect of Maternal Obesity on Placental Cell-Free DNA Release in a Mouse Model. Reprod. Sci. 26, 1218–1224 (2019). https://doi.org/10.1177/1933719118811647

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