Use of a Mouse In Vitro Fertilization Model to Understand the Developmental Origins of Health and Disease Hypothesis

Feuer, Sky K.; Liu, Xiaowei; Donjacour, Annemarie A.; Lin, Wen; Simbulan, Rhodel; Giritharan, G.; Piane, Luisa Delle; Kolahi, Kevin S.; Ameri, Kurosh; Maltepe, Emin; Rinaudo, Paolo

doi:10.1210/en.2013-2081

Cited by 119 publications

(178 citation statements)

References 60 publications

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“…There are several reports pointing out that IVF may relate with abnormal emotional behaviors in adult mouse offspring [60–64]. In this study, Sey/+ mice born from IVF showed decreased USV vocalizations and less anxiety, which is similar to rSey 2 /+ rats born from natural mating [37].…”

Section: Discussionsupporting

confidence: 61%

Paternal Aging Affects Behavior in Pax6 Mutant Mice: A Gene/Environment Interaction in Understanding Neurodevelopmental Disorders

et al. 2016

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Neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit and hyperactivity disorder (ADHD) have increased over the last few decades. These neurodevelopmental disorders are characterized by a complex etiology, which involves multiple genes and gene-environmental interactions. Various genes that control specific properties of neural development exert pivotal roles in the occurrence and severity of phenotypes associated with neurodevelopmental disorders. Moreover, paternal aging has been reported as one of the factors that contribute to the risk of ASD and ADHD. Here we report, for the first time, that paternal aging has profound effects on the onset of behavioral abnormalities in mice carrying a mutation of Pax6, a gene with neurodevelopmental regulatory functions. We adopted an in vitro fertilization approach to restrict the influence of additional factors. Comprehensive behavioral analyses were performed in Sey/+ mice (i.e., Pax6 mutant heterozygotes) born from in vitro fertilization of sperm taken from young or aged Sey/+ fathers. No body weight changes were found in the four groups, i.e., Sey/+ and wild type (WT) mice born to young or aged father. However, we found important differences in maternal separation-induced ultrasonic vocalizations of Sey/+ mice born from young father and in the level of hyperactivity of Sey/+ mice born from aged fathers in the open-field test, respectively, compared to WT littermates. Phenotypes of anxiety were observed in both genotypes born from aged fathers compared with those born from young fathers. No significant difference was found in social behavior and sensorimotor gating among the four groups. These results indicate that mice with a single genetic risk factor can develop different phenotypes depending on the paternal age. Our study advocates for serious considerations on the role of paternal aging in breeding strategies for animal studies.

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Section: Discussionsupporting

confidence: 61%

Paternal Aging Affects Behavior in Pax6 Mutant Mice: A Gene/Environment Interaction in Understanding Neurodevelopmental Disorders

et al. 2016

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“…In some studies, only female mice exhibited metabolic effects in response to ART procedures [66,67]. IVF and ICSI female offspring displayed impaired glucose tolerance compared to naturally conceived controls, while no effects were detected in IVF or ICSI males [66].…”

Section: Evidence That Art Can Increase the Risk Of Cardiometabolimentioning

confidence: 99%

Can assisted reproductive technologies cause adult-onset disease? Evidence from human and mouse

Vrooman

Bartolomei

2017

Reproductive Toxicology

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Millions of children have been born worldwide though assisted reproductive technologies (ART). Consistent with the Developmental Origins of Health and Disease hypothesis, there is concern that ART can induce adverse effects, especially because procedures coincide with epigenetic reprogramming events. Although the majority of studies investigating the effects of ART have focused on perinatal outcomes, more recent studies demonstrate that ART-conceived children may be at increased risk for postnatal effects. Here, we present the current epidemiological evidence that ART-conceived children have detectable differences in blood pressure, body composition, and glucose homeostasis. Similar effects are observed in the ART mouse model, which have no underlying infertility, suggesting that cardiometabolic effects are likely caused by ART procedures and not due to reasons related to infertility. We propose that the mouse system can, consequently, be used to adequately study, modify, and improve outcomes for ART children.

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“…During embryonic development, organisms exhibit a high level of developmental plasticity allowing for alterations of the genetic landscape in response to the surrounding environment which can ultimately result in a broad range of adult phenotypes (Feuer et al 2014). It is within these genetic and epigenetic alterations that an increased risk of developing diseases in adulthood occurs.…”

Section: Introductionmentioning

confidence: 99%

Developmental origins of neurotransmitter and transcriptome alterations in adult female zebrafish exposed to atrazine during embryogenesis

et al. 2015

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Atrazine is an herbicide applied to agricultural crops and is indicated to be an endocrine disruptor. Atrazine is frequently found to contaminate potable water supplies above the maximum contaminant level of 3 µg/L as defined by the U. S. Environmental Protection Agency. The developmental origin of adult disease hypothesis suggests that toxicant exposure during development can increase the risk of certain diseases during adulthood. However, the molecular mechanisms underlying disease progression are still unknown. In this study, zebrafish embryos were exposed to 0, 0.3, 3, or 30 µg/L atrazine throughout embryogenesis. Larvae were then allowed to mature under normal laboratory conditions with no further chemical treatment until 7 days post fertilization (dpf) or adulthood and neurotransmitter analysis completed. No significant alterations in neurotransmitter levels was observed at 7 dpf or in adult males, but a significant decrease in 5-Hydroxyindoleacetic acid (5-HIAA) and serotonin turnover was seen in adult female brain tissue. Transcriptomic analysis was completed on adult female brain tissue to identify molecular pathways underlying the observed neurological alterations. Altered expression of 1853, 84, and 419 genes in the females exposed to 0.3, 3, or 30 µg/L atrazine during embryogenesis were identified, respectively. There was a high level of overlap between the biological processes and molecular pathways in which the altered genes were associated. Moreover, a subset of genes was down regulated throughout the serotonergic pathway. These results provide support of the developmental origins of neurological alterations observed in adult female zebrafish exposed to atrazine during embryogenesis.

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Use of a Mouse In Vitro Fertilization Model to Understand the Developmental Origins of Health and Disease Hypothesis

Cited by 119 publications

References 60 publications

Paternal Aging Affects Behavior in Pax6 Mutant Mice: A Gene/Environment Interaction in Understanding Neurodevelopmental Disorders

Paternal Aging Affects Behavior in Pax6 Mutant Mice: A Gene/Environment Interaction in Understanding Neurodevelopmental Disorders

Can assisted reproductive technologies cause adult-onset disease? Evidence from human and mouse

Developmental origins of neurotransmitter and transcriptome alterations in adult female zebrafish exposed to atrazine during embryogenesis

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