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

• Published in: Reproductive sciences (Thousand Oaks, Calif.) Calif.), 2015-01, Vol.22 (1), p.23-30
• Main Authors: Strata, Fabrizio, Giritharan, Gnanaratnam, Sebastiano, Francesca Di, Piane, Luisa Delle, Kao, Chia-Ning, Donjacour, Annemarie, Rinaudo, Paolo
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Anxiety - etiology; Anxiety - genetics; Anxiety - metabolism; Anxiety - prevention & control; Anxiety - psychology; Behavior, Animal; Birth Weight; Blastocyst - metabolism; Blastocyst - pathology; Brain - metabolism; Diet, Western - adverse effects; Embryo Culture Techniques; Embryology; Female; Fertilization in Vitro - adverse effects; Gene Expression Regulation; Male; Maternal Nutritional Physiological Phenomena; Medicine & Public Health; Mice, Inbred C57BL; Monoamine Oxidase - genetics; Monoamine Oxidase - metabolism; Motor Activity; Nutritional Status; Obstetrics/Perinatology/Midwifery; Oocyte Retrieval; Original; Original Article; Pregnancy; Prenatal Exposure Delayed Effects; Protective Factors; Receptors, GABA - genetics; Receptors, GABA - metabolism; Reproductive Medicine; Risk Factors; Stress, Physiological; Time Factors
• ISSN: 1933-7191; 1933-7205
• DOI: 10.1177/1933719114557900

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.