Behavior and brain gene expression changes in mice exposed to preimplantation and prenatal stress.
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.
Dept. of Reproductive Science, University of California San Francisco, San Francisco, CA, USA Dept. Neuroscience, Med. School, Parma University, Parma, Italy.
Fabrizio
F
Strata
Dept. of Reproductive Science, University of California San Francisco, San Francisco, CA, USA.
Gnanaratnam
G
Giritharan
Ospedale Spirito Santo, Pescara, Italy.
Francesca Di
FD
Sebastiano
Reproductive Medicine and IVF Unit, Torino, Italy.
Luisa Delle
LD
Piane
Dept. of Reproductive Science, University of California San Francisco, San Francisco, CA, USA.
Chia-Ning
CN
Kao
Dept. of Reproductive Science, University of California San Francisco, San Francisco, CA, USA.
Annemarie
A
Donjacour
Dept. of Reproductive Science, University of California San Francisco, San Francisco, CA, USA rinaudop@obgyn.ucsf.edu.
Paolo
P
Rinaudo
D000367:Age Factors; D000818:Animals; D001007:Anxiety / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control / Q000523:psychology; D001522:Behavior, Animal; D001724:Birth Weight; D001755:Blastocyst / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism*; D066273:Diet, Western / Q000009:adverse effects; D046149:Embryo Culture Techniques; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects*; D005786:Gene Expression Regulation; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism; D009043:Motor Activity; D009752:Nutritional Status; D054315:Oocyte Retrieval; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D065840:Protective Factors; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D013312:Stress, Physiological; D013997:Time Factors
D018079:Receptors, GABA; D008995:Monoamine Oxidase
DOHaD; IVF; assisted reproductive technologies