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Behavior and Brain Gene Expression Changes in Mice Exposed to Preimplantation and Prenatal Stress

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Abstract

Preimplantation culture of mouse embryos has been suggested to result in reduced anxiety-like behavior in adulthood. Here, we investigated the effects of in vitro fertilization (IVF), embryo culture, and different diets on anxiety-like behavior using the elevated plus maze (EPM). We hypothesized that exposure to suboptimal conditions during the preimplantation stage would interact with the suboptimal diet to alter behavior. The expression of genes related to anxiety was then assessed by quantitative real-time polymerase chain reaction in various brain regions. When fed a normal diet during gestation and a moderately high-fat Western diet (WD) postnatally, naturally conceived (NC) and IVF mice showed similar anxiety-like behavior on the EPM. However, when fed a low-protein diet prenatally and a high-fat diet postnatally (LP/HF), NC mice showed a modest increase in anxiety-like behavior, whereas IVF mice showed the opposite: a strongly reduced anxiety-like behavior on the EPM. The robust reduction in anxiety-like behavior in IVF males fed the LP/HF diets was, intriguingly, associated with reduced expression of MAO-A, CRFR2, and GABA markers in the hypothalamus and cortex. These findings are discussed in relation to the developmental origin of health and disease hypothesis and the 2-hit model, which suggests that 2 events, occurring at different times in development, can act synergistically with long-term consequences observed during adulthood.

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Authors and Affiliations

  1. Dept. of Reproductive Science, University of California San Francisco, 2356 Sutter St, 7th Floor, 94115, San Francisco, CA, USA

    Fabrizio Strata MD, PhD, Gnanaratnam Giritharan PhD, Chia-Ning Kao MS, Annemarie Donjacour PhD & Paolo Rinaudo MD PhD

  2. Dept. Neuroscience, Med. School, Parma University, Parma, Italy

    Fabrizio Strata MD, PhD

  3. Ospedale Spirito Santo, Pescara, Italy

    Francesca Di Sebastiano MD

  4. Reproductive Medicine and IVF Unit, Torino, Italy

    Luisa Delle Piane MD, PhD

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  1. Fabrizio Strata MD, PhD
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  2. Gnanaratnam Giritharan PhD
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  3. Francesca Di Sebastiano MD
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  4. Luisa Delle Piane MD, PhD
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  6. Annemarie Donjacour PhD
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Correspondence to Paolo Rinaudo MD PhD.

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Strata, F., Giritharan, G., Sebastiano, F.D. et al. Behavior and Brain Gene Expression Changes in Mice Exposed to Preimplantation and Prenatal Stress. Reprod. Sci. 22, 23–30 (2015). https://doi.org/10.1177/1933719114557900

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