scholarly journals Cardiometabolic Phenotypic Differences in Male Offspring Born to Obese Preeclamptic-Like BPH/5 Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Kalie F. Beckers ◽  
Viviane C. L. Gomes ◽  
Kassandra J. Raven Crissman ◽  
Daniella M. Adams ◽  
Chin-Chi Liu ◽  
...  
Keyword(s):  
Adult Male ◽  
Maternal Obesity ◽  
Gestational Hypertension ◽  
Female Offspring ◽  
Left Ventricular ◽  
Male Offspring ◽  
Hypertensive Disorder ◽  
Male And Female ◽  
Similar Body ◽  
The Impact

Preeclampsia (PE) is a hypertensive disorder of pregnancy occurring in approximately 10% of women worldwide. While it is life threatening to both the mother and baby, the only effective treatment is delivery of the placenta and fetus, which is often preterm. Maternal obesity is a risk factor for PE, and the effects of both on offspring are long standing with increased incidence of cardiometabolic disease in adulthood. Obese BPH/5 mice spontaneously exhibit excessive gestational weight gain and late-gestational hypertension, similar to women with PE, along with fetal growth restriction and accelerated compensatory growth in female offspring. We hypothesized that BPH/5 male offspring will demonstrate cardiovascular and metabolic phenotypes similar to BPH/5 females. As previously described, BPH/5 females born to ad libitum-fed dams are overweight with hyperphagia and increased subcutaneous, peri-renal, and peri-gonadal white adipose tissue (WAT) and cardiomegaly compared to age-matched adult female controls. In this study, BPH/5 adult male mice have similar body weights and food intake compared to age-matched control mice but have increased inflammatory subcutaneous and peri-renal WAT and signs of cardiovascular disease: left ventricular hypertrophy and hypertension. Therefore, adult male BPH/5 do not completely phenocopy the cardiometabolic profile of female BPH/5 mice. Future investigations are necessary to understand the differences observed in BPH/5 male and female mice as they age. In conclusion, the impact of fetal programming due to PE has a transgenerational effect on both male and female offspring in the BPH/5 mouse model. The maternal obesogenic environment may play a role in PE pregnancy outcomes, including offspring health as they age.

scholarly journals Exposure to maternal obesity programs sex differences in pancreatic islets of the offspring in mice

Diabetologia ◽  
2019 ◽  
Vol 63 (2) ◽  
pp. 324-337 ◽  
Author(s):  
Lisa M. Nicholas ◽  
Mototsugu Nagao ◽  
Laura C. Kusinski ◽  
Denise S. Fernandez-Twinn ◽  
Lena Eliasson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Mitochondrial Respiration ◽  
Caspase 3 ◽  
Maternal Obesity ◽  
Female Offspring ◽  
Islet Function ◽  
Male And Female ◽  
The Impact

Abstract Aims/hypothesis Obesity during pregnancy increases offspring type 2 diabetes risk. Given that nearly half of women of child-bearing age in many populations are currently overweight/obese, it is key that we improve our understanding of the impact of the in utero/early life environment on offspring islet function. Whilst a number of experimental studies have examined the effect of maternal obesity on offspring islet architecture and/or function, it has not previously been delineated whether these changes are independent of other confounding risk factors such as obesity, postnatal high-fat-feeding and ageing. Thus, we aimed to study the impact of exposure to maternal obesity on offspring islets in young, glucose-tolerant male and female offspring. Methods Female C57BL/6J mice were fed ad libitum either chow or obesogenic diet prior to and throughout pregnancy and lactation. Offspring were weaned onto a chow diet and remained on this diet until the end of the study. An IPGTT was performed on male and female offspring at 7 weeks of age. At 8 weeks of age, pancreatic islets were isolated from offspring for measurement of insulin secretion and content, mitochondrial respiration, ATP content, reactive oxygen species levels, beta and alpha cell mass, granule and mitochondrial density (by transmission electron microscopy), and mRNA and protein expression by real-time RT-PCR and Western blotting, respectively. Results Glucose tolerance was similar irrespective of maternal diet and offspring sex. However, blood glucose was lower (p < 0.001) and plasma insulin higher (p < 0.05) in female offspring of obese dams 15 min after glucose administration. This was associated with higher glucose- (p < 0.01) and leucine/glutamine-stimulated (p < 0.05) insulin secretion in these offspring. Furthermore, there was increased mitochondrial respiration (p < 0.01) and density (p < 0.05) in female offspring of obese dams compared with same-sex controls. Expression of mitochondrial and nuclear-encoded components of the electron transport chain, L-type Ca2+ channel subtypes that play a key role in stimulus-secretion coupling [Cacna1d (p < 0.05)], and oestrogen receptor α (p < 0.05) was also increased in islets from these female offspring of obese dams. Moreover, cleaved caspase-3 expression and BAX:Bcl-2 were decreased (p < 0.05) reflecting reduced susceptibility to apoptosis. In contrast, in male offspring, glucose and leucine/glutamine-stimulated insulin secretion was comparable between treatment groups. There was, however, compromised mitochondrial respiration characterised by decreased ATP synthesis-driven respiration (p < 0.05) and increased uncoupled respiration (p < 0.01), reduced docked insulin granules (p < 0.001), decreased Cacna1c (p < 0.001) and Cacna1d (p < 0.001) and increased cleaved caspase-3 expression (p < 0.05). Conclusions/interpretation Maternal obesity programs sex differences in offspring islet function. Islets of female but not male offspring appear to be primed to cope with a nutritionally-rich postnatal environment, which may reflect differences in future type 2 diabetes risk.

scholarly journals Prenatal cocaine exposure abolished ischemic preconditioning-induced protection in adult male rat hearts: role of PKCε

2009 ◽  
Vol 296 (5) ◽  
pp. H1566-H1576 ◽  
Author(s):  
Kurt D. Meyer ◽  
Haitao Zhang ◽  
Lubo Zhang
Keyword(s):  
Adult Male ◽  
Ischemic Preconditioning ◽  
Female Offspring ◽  
Left Ventricular ◽  
Male Offspring ◽  
Male Rat ◽  
Saline Control ◽  
Cocaine Exposure ◽  
Prenatal Cocaine Exposure ◽  
Prenatal Cocaine

Prenatal cocaine exposure in rats resulted in decreased PKCε protein expression in the heart of adult male but not female offspring. The present study determined its functional consequence of inhibiting cardioprotection mediated by ischemic preconditioning. Pregnant Sprague-Dawley rats were administered intraperitoneally saline or cocaine (30 mg·kg−1·day−1) from day 15 to day 21 of gestational age. Hearts were isolated from 3-mo-old offspring and were subjected to ischemia and reperfusion injury in a Langendorff preparation, with or without prior ischemic preconditioning. Preischemic values of left ventricular function were the same between the saline control and cocaine-treated animals. Ischemic preconditioning of two episodes of 5-min ischemia significantly decreased infarct size and enhanced postischemic functional recovery of the left ventricle in the saline control animals. This ischemic preconditioning was associated with increased phospho-PKCε, but not phospho-PKCδ, levels and was blocked by a PKCε translocation inhibitor peptide. Prenatal cocaine treatment abolished the ischemic preconditioning-mediated increase in phospho-PKCε and cardioprotection in the heart of male offspring. In contrast, the cardioprotective effect was fully maintained in female offspring that were exposed to cocaine before birth. The results suggest that prenatal cocaine exposure causes a sex-specific loss of cardioprotection by ischemic preconditioning in adult offspring, which is most likely due to fetal programming of PKCε gene repression, resulting in a downregulation of PKCε function in the heart of adult male offspring.

scholarly journals Exposure to maternal obesityper seprograms sex-differences in pancreatic islets of the offspring

2019 ◽  
Author(s):  
L M Nicholas ◽  
M Nagao ◽  
L C Kusinski ◽  
D S Fernandez-Twinn ◽  
L Eliasson ◽  
...  
Keyword(s):  
Sex Differences ◽  
Mitochondrial Respiration ◽  
Maternal Obesity ◽  
Atp Synthesis ◽  
Estrogen Receptor Α ◽  
Female Offspring ◽  
Male Offspring ◽  
Islet Function ◽  
Postnatal Environment ◽  
The Impact

SummaryMaternal obesity increases type 2 diabetes (T2D) risk in the offspring. Given that nearly half of women of child-bearing age in many populations are currently overweight/obese, it is key that we improve our understanding of the impact of thein utero/early life environment on offspring islet function. Using a well-established mouse model of diet-induced obesity, we examined offspring islets before the onset of metabolic dysfunction. This allowed us to determine inherent changes, in males and females, which are distinct from the response of islets to an existing obesogenic, insulin resistant milieu hence identifying islet dysregulation reflecting very early manifestation of the disease before the onset of disrupted glucose homeostasis. Female offspring of obese dams displayed higher glucose-stimulated insulin secretion and mitochondrial respiration, increased expression of estrogen receptor α and decreased cleaved-caspase 3 and Bax:Bcl-2 reflecting reduced susceptibility to apoptosis. In contrast, male offspring of obese dams displayed compromised mitochondrial respiration characterised by decreased ATP synthesis-driven respiration and increased “uncoupled” respiration and reduced docked insulin granules in β-cells. Thus, maternal obesity “programs” sex-differences in offspring islet function. Islets of female but not male offspring appear primed to cope with a nutritionally-rich postnatal environment, which may reflect differences in future T2D risk.

Abstract P217: Phenotypic Difference Exist Between Bph/5 Offspring In A Sex-dependent Manner

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Kalie Beckers ◽  
Viviane Gomes ◽  
Kat Robillard ◽  
Chin-CHi Liu ◽  
Andrea Johnston ◽  
...  
Keyword(s):  
Maternal Obesity ◽  
Gestational Hypertension ◽  
Female Offspring ◽  
Hypertensive Disorder ◽  
Dependent Manner ◽  
Obesogenic Environment ◽  
Maternal Weight ◽  
Phenotypic Analysis ◽  
Phenotypic Differences ◽  
In Pregnancy

Preeclampsia (PE) is a hypertensive disorder of pregnancy occurring in ~10% of women worldwide. Maternal obesity is a risk factor for PE and the effects on offspring are long-standing with increased incidence of cardiometabolic disease into adulthood. The maternal obesogenic environment may play a role in pregnancy outcomes and offspring in a sex-dependent manner; however, in the context of superimposed PE, it is not completely understood. Obese BPH/5 mice spontaneously exhibit late-gestational hypertension, fetal demise and growth restriction, and excessive gestational weight gain, similar to PE. We hypothesized that phenotypic differences exist between female and male BPH/5 offspring and maternal weight loss in BPH/5 during pregnancy would influence these phenotypic differences. Obese BPH/5 dams were calorie restricted via pair-feeding (PF) to match the food intake of C57 dams for the first 9 days of pregnancy. Offspring were fed an ad libitum (lib) diet until phenotypic analysis. Body weights (BW), visceral peri-gonadal and peri-renal white adipose tissue (WAT), hearts, and livers were recorded in BPH/5 and control C57 age-matched adult females and males born to ad lib fed and PF dams. Values are reported as mean ± standard error of the mean. As previously described, BPH/5 females born to ad lib fed dams are overweight with increased peri-renal and gonadal WAT, cardiomegaly, and hepatomegaly (1308 ±13.3 vs 979.9 ±82.3g in C57, p<0.05). BPH/5 male mice are underweight (23.8±1.6 vs C57: 27.9±1.6g) with increased peri-renal WAT (158± 23 vs C57: 53.25±10.3mg, p<0.05), and cardiomegaly (heart: BW 8.1±0.5 vs C57: 5.7±1.1, p<0.05). Without altering BPH/5 male or female offspring BW, peri-renal adiposity (males: 103.5±13mg, females: 73.2±10.3mg, p<0.05), cardiomegaly (males: 5.74±0.5, females: 6.03±0.4, p<0.05), and female hepatomegaly (1149.8 ±58.1mg, p<0.05) are significantly attenuated in PF BPH/5 dams. To conclude, reduction in the maternal obesogenic environment may play a role in BPH/5 sex-dependent phenotypic differences. Future investigations are necessary to understand the differences observed in BPH/5 male versus female mice into adulthood as well as the transgenerational impact of attenuated maternal obesity in pregnancy.

Abstract P230: Prevention Of Maternal Obesity Attenuates Adverse Offspring Cardiometabolic Outcomes In Preeclamptic-like Mouse Model

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Kalie Beckers ◽  
Juliet Flanagan ◽  
Viviane Gomes ◽  
ChinCHi Liu ◽  
Andrea Johnston ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Cardiometabolic Risk ◽  
Maternal Obesity ◽  
Fold Increase ◽  
Female Offspring ◽  
Fetal Mortality ◽  
Hypertensive Disorder ◽  
Dependent Manner ◽  
Daily Food ◽  
Similar Body

Preeclampsia (PE) is a hypertensive disorder of pregnancy and a leading cause of maternal and fetal mortality with maternal obesity as a risk factor. Decreasing white adipose tissue (WAT) via calorie restriction during the first half of pregnancy may alter the maternal-fetal environment to improve offspring outcomes. We hypothesized that pair-feeding BPH/5 dams during pregnancy will improve cardiometabolic risk and WAT pro-inflammatory cytokine expression in BPH/5 offspring in a sex-dependent manner. Previously, we showed that BPH/5 males, unlike females, have similar body weights, daily food intake, and circulating leptin levels as compared to age-matched control mice. Although, adult BPH/5 females and males have cardiomegaly and increased subcutaneous and peri-renal WAT mass compared to lean control mice. To investigate the prevention of maternal obesity on offspring outcomes, BPH/5 dams were pair-fed (PF) beginning at embryonic day (e)0.5 to C57 pregnant mice. Offspring cardiometabolic risk and WAT pro-inflammatory cytokine mRNA were measured using real time PCR in adult ad libitum fed offspring. Compared to controls, peri-renal WAT from BPH/5 males showed a 5-fold increase while females had a 15-fold increase in TNFa (n=3-6; p<0.05), 6-fold increase in PTGS-2 for males and 5-fold increase for females (n=3-6; p<0.05), and 3-fold increase in IL-6 for males and 1.25-fold increase for females (n=3-6; p<0.05) in subcutaneous WAT. Adult offspring born to PF BPH/5 dams had decreased expression in TNFa (male: 4-fold and female: 7-fold), PTGS-2 (male: 5-fold and female: 4-fold), and IL-6 (male: 10-fold; n=3-6; p<0.05). In conclusion, prevention of maternal obesity in BPH/5 dams attenuates cardiometabolic risks and reduces the pro-inflammatory WAT milieu in male and female offspring. The transgenerational effects during pregnancy is believed to be caused by an alteration in the maternal-fetal environment due to WAT pro-inflammatory adipokines. Future investigations are necessary to understand the differences observed in BPH/5 male versus female mice into adulthood as well as the transgenerational impact of attenuated maternal obesity in pregnancy.

Placental treatment improves cardiac tolerance to ischemia/reperfusion insult in adult male and female offspring exposed to prenatal hypoxia

2021 ◽  
Vol 165 ◽  
pp. 105461
Author(s):  
Nataliia Hula ◽  
Floor Spaans ◽  
Jennie Vu ◽  
Anita Quon ◽  
Raven Kirschenman ◽  
...  
Keyword(s):  
Adult Male ◽  
Ischemia Reperfusion ◽  
Female Offspring ◽  
Prenatal Hypoxia ◽  
Male And Female

scholarly journals The impact of maternal obesity on maternal and fetal outcome

2019 ◽  
Vol 9 (1) ◽  
pp. 104
Author(s):  
Esther Kamalarani A. ◽  
Ramyajothi . ◽  
Ramalakshmi S.
Keyword(s):  
Developing Countries ◽  
Adverse Effects ◽  
Maternal Obesity ◽  
Gestational Hypertension ◽  
Developed Countries ◽  
Fetal Outcome ◽  
Health Concern ◽  
The Past ◽  
Group 2 ◽  
The Impact

Background: Obesity continues to be a global health concern. Although the increasing obesity rates in developed countries has slowed down in the past 10 years, obesity rates in developing countries continue to increase, as much as three times in some developing countries over the past 30 years. The aim of the study was to determine the adverse effects of obesity in pregnancy and maternal and fetal outcome.Methods: In all patients, a detailed history was taken and examinations and investigations were carried out.  Based on BMI (body mass index), patients were divided into 2 groups. Group 1 = patients with BMI >30 kg/m2 and Group 2 = patients with BMI <30 kg /m2.Results: In our study, comparing pregnant mothers with BMI >30 kg/m2 and normal BMI, authors found that the prevalence of maternal and fetal complications was higher in the obese group. Prevalence of antenatal complications like gestational hypertension, preeclampsia, imminent eclampsia and gestational diabetes mellitus requiring control with insulin was higher in obese women.Conclusions: Obesity is associated with increased adverse effects on pregnancy and its outcome.

scholarly journals Programming effects of maternal and gestational obesity on offspring metabolism and metabolic inflammation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
E. Chang ◽  
H. Hafner ◽  
M. Varghese ◽  
C. Griffin ◽  
J. Clemente ◽  
...  
Keyword(s):  
Body Composition ◽  
Adipose Tissue ◽  
Maternal Obesity ◽  
Immune Cell ◽  
Female Offspring ◽  
Normal Diet ◽  
Male Offspring ◽  
Reproductive Age ◽  
Metabolic Inflammation ◽  
Significant Difference

Abstract With the increasing prevalence of obesity in women of reproductive age there is a need to understand the ramifications of this on offspring. The purpose of this study is to investigate the programming effects of maternal obesity during preconception and the preconception/gestational period on adiposity and adipose tissue inflammation in offspring using an animal model. Adult female C57Bl/6J mice were assigned either normal diet, high fat diet (HFD) prior to pregnancy, or HFD prior to and through pregnancy. Some offspring were maintained on normal diet while others started HFD later in life. Offspring were assessed for body composition and metabolic responses. Lipid storing tissues were evaluated for expansion and inflammation. Male offspring from the preconception group had the greatest weight gain, most subcutaneous adipose tissue, and largest liver mass when introduced to postnatal HFD. Male offspring of the preconception/gestation group had worsened glucose tolerance and an increase in resident (CD11c−) adipose tissue macrophages (ATMs) when exposed to postnatal HFD. Female offspring had no significant difference in any parameter between the diet treatment groups. In conclusion, this study demonstrates that prenatal and pregnancy windows have independent programming effects on offspring. Preconception exposure affects body composition and adiposity while gestation exposure affects metabolism and tissue immune cell phenotypes.

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