Effects of Prenatal Hypoxia on Nervous System Development and Related Diseases

Wang, Bin; Zeng, Hongtao; Liu, Jingliu; Sun, Miao

doi:10.3389/fnins.2021.755554

Cited by 47 publications

(22 citation statements)

References 122 publications

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“…In recent years, animal models of prenatal hypoxia have been widely used to understand the molecular mechanisms of adverse outcomes in offspring. Prenatal hypoxia affects fetal growth and elicits many disturbances after birth including the development of the central nervous system and cardiovascular regulatory system ( Peyronnet et al, 2000 ; Wang et al, 2021 ; Sutovska et al, 2022 ). Decreased oxygen supply and peripheral blood flow by gestational IH to the fetal organs such as the heart and brain have critical impacts on physiological functions of these organs ( Baschat et al, 1997 ).…”

Section: Introductionmentioning

confidence: 99%

Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia

et al. 2023

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Gestational intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea that occurs frequently during pregnancy, and effects caused by this environmental change during pregnancy may be transmitted to the offspring. In this study, we aimed to clarify the effects of IH in pregnant rats on the skeletal muscle of adolescent offspring rats. Mother rats underwent IH from gestation day 7–21, and their 5-weeks-old male offspring were analyzed. All male offspring rats were born and raised under normoxia conditions. Although no general growth retardation was observed, we found that exposure to gestational IH reduces endurance running capacity of adolescent offspring rats. Both a respiratory muscle (diaphragm; DIA) and a limb muscle (tibialis anterior; TA) showed no histological abnormalities, including fiber size and fiber type distribution. To identify the possible mechanism underlying the reduced running capacity, regulatory factors associated with energy metabolism were analyzed in different parts of skeletal muscles. Compared with rats born under conditions of gestational normoxia, gestational IH offspring rats showed significantly lower expression of genes associated with glucose and lipid metabolism, and lower protein levels of phosphorylated AMPK and AKT. Furthermore, gene expression of adiponectin receptors one and two was significantly decreased in the DIA and TA muscles. In addition, the DIA muscle from adolescent rats had significantly decreased capillary density as a result of gestational IH. However, these changes were not observed in a sucking muscle (geniohyoid) and a masticating muscle (masseter) of these rats. These results suggest that respiratory and limb muscles are vulnerable to gestational IH, which induces altered energy metabolism with decreased aerobic motor function. These changes were partially owing to the decreased expression of adiponectin receptors and decreased capillary density in adolescent offspring rats.

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Section: Introductionmentioning

confidence: 99%

Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia

et al. 2023

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“…For example, Vázquez-Borsetti et al (2016) reported that a 20-min hypoxia-ischemia insult on perinatal rats led to social deficits and loss of neurons. However, hypoxia studies on prenatal and perinatal rodents often apply artery ligation to induce hypoxia-ischemia exposure ( Wang et al, 2021a ), which is much harsher than the hypoxia treatment in our study. Driscoll et al (2018) showed that 10% oxygen applied on pregnant Sprague-Dawley rats transiently for 3, 5, or 7 min combined with ligation of the infra-renal abdominal aorta and uterine arteries caused social deficits and inflammation in postcesarean pups at postnatal day 30.…”

Section: Discussionmentioning

confidence: 99%

Intermittent hypoxia-induced enhancement of sociability and working memory associates with CNTNAP2 upregulation

Zhang

Yang

et al. 2023

Front. Mol. Neurosci.

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IntroductionHypoxia is an environmental risk factor for many disorders throughout life. Perinatal hypoxia contributes to autism spectrum disorder (ASD), while hypoxic conditions in the elderly facilitate memory deficits. However, the effects of hypoxia on adolescence remains elusive. CNTNAP2 is a critical molecule in ASD pathogenesis with undefined mechanisms. We investigate hypoxia’s impact on adolescence and the underlying mechanism related to CNTNAP2.MethodsThree-chamber social approach test, Y maze, Morris Water Maze and Open Field Test were applied to evaluate behavioral alterations. Immunoblotting, 5′- RACE and dual-luciferase reporter assay were performed to examine CNTNAP2 protein expression, transcription start site (TSS) of human CNTNAP2 gene and CNTNAP2 promoter activity, respectively.ResultsIntermittent hypoxia treatment improved social behaviors and working memory in adolescent mice. CNTNAP2 was increased in the brains of hypoxia-treated mice. The sequencing results identified the TSS at 518 bp upstream of the translation start site ATG. Hypoxia upregulated CNTNAP2 by interacting with functional hypoxia response elements in CNTNAP2 promoter.ConclusionIntermittent hypoxia enhanced sociability and working memory associated with CNTNAP2 upregulation. Our study provides novel insights into intermittent hypoxia’s impact on development and the interaction between genetic and environmental risk factors in ASD pathogenesis.

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“…Hypoxia has been associated with other psychiatric disorders including schizophrenia and other non‐affective psychoses (Zornberg et al, 2000), but the exact mechanisms underlying this phenomenon are not clear. Altered epigenetic programming, endocrine axis dysfunction, and oxidative damage are hypothesized to be underlying mechanisms linking prenatal hypoxia with abnormal brain development and plasticity (reviewed in Wang et al, 2021). Thus, we cannot exclude that the link between low Apgar and offspring AN is hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Exposures during pregnancy and at birth are associated with the risk of offspring eating disorders

Ozsvar,

Gissler,

Lavebratt

et al. 2023

Intl J Eating Disorders

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BackgroundEating disorders (ED) are severe psychiatric disorders, commonly debuting early. Aberrances in the intrauterine environment and at birth have been associated with risk of ED. Here, we explore if, and at what effect size, a variety of such exposures associate with offspring ED, that is, anorexia nervosa (AN), bulimia nervosa (BN), and eating disorder not otherwise specified (EDNOS).MethodsThis population‐based cohort study, conducted from September 2021 to August 2023, used Finnish national registries of all live births in 1996–2014 (N = 1,097,753). Cox proportional hazards modeling was used to compare ED risk in exposed versus unexposed offspring, adjusting for potential confounders and performing sex‐stratified analyses.ResultsA total of 6614 offspring were diagnosed with an ED; 3668 AN, 666 BN, and 4248 EDNOS. Lower risk of offspring AN was seen with young mothers, continued smoking, and instrumental delivery, while higher risk was seen with older mothers, inflammatory disorders, prematurity, small for gestational age, and low Apgar. Offspring risk of BN was higher with continued smoking and prematurity, while lower with postmature birth. Offspring risk of EDNOS was lower with instrumental delivery, higher for older mothers, polycystic ovary syndrome, insulin‐treated pregestational diabetes, antibacterial treatment, prematurity, and small for gestational age. Sex‐specific associations were found.ConclusionsSeveral prenatal and at birth exposures are associated with offspring ED; however, we cannot exclude confounding by maternal BMI. Nevertheless, several exposures selectively associate with risk of either AN, BN, or EDNOS, and some are sex‐specific, emphasizing the importance of subtype‐ and sex‐stratified analyses of ED.Public SignificanceWe define environmental factors involved in the development of different ED, of importance as preventive measure, but also in order to aid in defining the molecular pathways involved and thus in the longer perspective contribute to the development of pharmacological treatment of ED.

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Effects of Prenatal Hypoxia on Nervous System Development and Related Diseases

Cited by 47 publications

References 122 publications

Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia

Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia

Intermittent hypoxia-induced enhancement of sociability and working memory associates with CNTNAP2 upregulation

Exposures during pregnancy and at birth are associated with the risk of offspring eating disorders

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