Developmental programming of peripheral diseases in offspring exposed to maternal obesity during pregnancy

Shrestha, Nirajan; Ezechukwu, Henry C.; Holland, Olivia J.; Hryciw, Deanne H.

doi:10.1152/ajpregu.00214.2020

Cited by 30 publications

(21 citation statements)

References 118 publications

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“…NAFLD) in offspring, both in rodent models and in humans. [9][10][11][12][13] It is unclear if the risk of severe NAFLD is also increased and if the effect of maternal obesity on liver-related disease in offspring can be confounded by other factors. An increase in risk could be explained partly by intrinsic maternal factors such as obesity, but possibly also by socioeconomic determinants.…”

Section: Maternal Obesity Increases the Risk And Severity Of Nafld In Offspring Introductionmentioning

confidence: 99%

Maternal obesity increases the risk and severity of NAFLD in offspring

Hagström

Simon

Roelstraete

et al. 2021

Journal of Hepatology

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Biopsy-proven NAFLD, Sweden, 1998Sweden, -2016 Maternal body mass index in early pregnancy165): Median maternal BMI 25.0 Obesity 19.3% Controls (n = 717): Median maternal BMI 23.3 Obesity 8.4% Odds ratio for any NAFLD in offspring to obese mothers: 3.26 Odds ratio for fibrotic NAFLD in offspring to obese mothers: 3.67 HighlightsMaternal obesity has been linked to NAFLD in offspring.All biopsy-proven NAFLD cases in Sweden aged 25 or younger were matched to controls.Data on maternal body mass index and socio-economic confounders were recorded.

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Section: Maternal Obesity Increases the Risk And Severity Of Nafld In Offspring Introductionmentioning

confidence: 99%

Maternal obesity increases the risk and severity of NAFLD in offspring

Hagström

Simon

Roelstraete

et al. 2021

Journal of Hepatology

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“…Meanwhile, Epidemiological analysis has demonstrated links between maternal obesity and offspring disease. The risk of organ de cits and related diseases caused by obesity has circular programming in subsequent generations [38]. In the current study, we have demonstrated that exposure to obesity and high-dose testosterone during pregnancy can cause severe metabolic disorders in adult female mice of PCOS offspring, mainly manifested by hyperandrogenemia and metabolic disorders, which centered on insulin resistance.…”

Section: Discussionmentioning

confidence: 55%

Effects of Exogenous Adiponectin Supplementation in Early Pregnant PCOS Mice on the Metabolic Syndrome of Adult Female Offspring

Zuo

Liao

Zhang

et al. 2020

Preprint

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Objective: PCOS is a heterogeneous endocrine disorder with both reproductive and metabolic abnormalities. At present, PCOS has been confirmed to have a certain genetic background. Compared with healthy women, the vast majority of PCOS patients have hyperandrogenemia, and this excessive androgen exposure during pregnancy may affect the development of female fetuses. The aim of the current study was to investigate the effect of adiponectin intervention during early pregnancy of obese mice with PCOS on the metabolic phenotype of adult female offspring.Methods: After the PCOS model was established, C57BL/6J mice were divided into maternal-control, maternal-PCOS, and maternal-PCOS+APN groups. DHEA-induced PCOS mice were supplemented with adiponectin (10 mg/kg/day) in the early pregnancy in order to eliminate adverse hormone exposure and then traced for endocrine indicators in their adult female offspring, which were observed for metabolism syndrome or endocrine disturbance and exhibited the main effects of APN. To further explore the underlying mechanism, the relative expressions of phosphorylated AMPK, PI3K, and Akt were detected in the ovaries of offspring mice.Results: The serum testosterone level of the maternal-PCOS+APN group in early pregnancy was significantly lower than that of the maternal-PCOS group (p < 0.01). The serum testosterone level in the offspring-PCOS+APN group was significantly lower than in the offspring-PCOS group (p＜0.05), the diestrus time characterized by massive granulocyte aggregation in the estrus cycle was significantly shorter than in the offspring-PCOS group (p＜0.05), and the phenotypes of PCOS-like reproductive disorders and metabolic disorders, such as obesity, insulin resistance, impaired glucose tolerance, and hyperlipidemia, were also significantly improved in the offspring-PCOS+APN group (p＜0.05). Compared with the control group, the expression levels of phosphorylated AMPK, PI3K, and Akt in the offspring-PCOS group were significantly decreased (p＜0.05), while those in the offspring-PCOS+APN group were significantly increased (p＜0.05).Conclusions: APN intervention in early pregnancy significantly reduced the adverse effects of maternal obesity and high androgen levels during pregnancy on female offspring and corrected the PCOS-like endocrine phenotype and metabolic disorders of adult female offspring. This effect may be caused by the activation of the AMPK/PI3K-Akt signaling pathway in PCOS offspring mice.

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“…Meanwhile, Epidemiological analysis has demonstrated links between maternal obesity and offspring disease. The risk of organ deficits and related diseases caused by obesity has circular programming in subsequent generations [ 38 ]. In the current study, we have demonstrated that exposure to obesity and high-dose testosterone during pregnancy can cause severe metabolic disorders in adult female mice of PCOS offspring, mainly manifested by hyperandrogenemia and metabolic disorders, which centered on insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Effects of exogenous adiponectin supplementation in early pregnant PCOS mice on the metabolic syndrome of adult female offspring

et al. 2021

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Objective PCOS is a heterogeneous endocrine disorder with both reproductive and metabolic abnormalities. At present, PCOS has been confirmed to have a certain genetic background. Compared with healthy women, the vast majority of PCOS patients have hyperandrogenemia, and this excessive androgen exposure during pregnancy may affect the development of female fetuses. The aim of the current study was to investigate the effect of adiponectin intervention during early pregnancy of obese mice with PCOS on the metabolic phenotype of adult female offspring. Methods After the PCOS model was established, C57BL/6J mice were divided into maternal-control, maternal-PCOS, and maternal-PCOS + APN groups. DHEA-induced PCOS mice were supplemented with adiponectin (10 mg/kg/day) in the early pregnancy in order to eliminate adverse hormone exposure and then traced for endocrine indicators in their adult female offspring, which were observed for metabolism syndrome or endocrine disturbance and exhibited the main effects of APN. To further explore the underlying mechanism, the relative expressions of phosphorylated AMPK, PI3K, and Akt were detected in the ovaries of offspring mice. Results The serum testosterone level of the maternal-PCOS + APN group in early pregnancy was significantly lower than that of the maternal-PCOS group (p < 0.01). The serum testosterone level in the offspring-PCOS + APN group was significantly lower than in the offspring-PCOS group (p <0.05), the diestrus time characterized by massive granulocyte aggregation in the estrus cycle was significantly shorter than in the offspring-PCOS group (p<0.05), and the phenotypes of PCOS-like reproductive disorders and metabolic disorders, such as obesity, insulin resistance, impaired glucose tolerance, and hyperlipidemia, were also significantly improved in the offspring-PCOS + APN group (p < 0.05). Compared with the control group, the expression levels of phosphorylated AMPK, PI3K, and Akt in the offspring-PCOS group were significantly decreased (p < 0.05), while those in the offspring-PCOS + APN group were significantly increased (p < 0.05). Conclusions APN intervention in early pregnancy significantly reduced the adverse effects of maternal obesity and high androgen levels during pregnancy on female offspring and corrected the PCOS-like endocrine phenotype and metabolic disorders of adult female offspring. This effect may be caused by the activation of the AMPK/PI3K-Akt signaling pathway in PCOS offspring mice.

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Developmental programming of peripheral diseases in offspring exposed to maternal obesity during pregnancy

Cited by 30 publications

References 118 publications

Maternal obesity increases the risk and severity of NAFLD in offspring

Maternal obesity increases the risk and severity of NAFLD in offspring

Effects of Exogenous Adiponectin Supplementation in Early Pregnant PCOS Mice on the Metabolic Syndrome of Adult Female Offspring

Effects of exogenous adiponectin supplementation in early pregnant PCOS mice on the metabolic syndrome of adult female offspring

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