scholarly journals Adverse metabolic phenotype of female offspring exposed to preeclampsia in utero: a characterization of the BPH/5 mouse in postnatal life

2017 ◽  
Vol 312 (4) ◽  
pp. R485-R491 ◽  
Author(s):  
Elizabeth F. Sutton ◽  
Heinrich E. Lob ◽  
Jiunn Song ◽  
YunWei Xia ◽  
Scott Butler ◽  
...  
Keyword(s):  
Early Adulthood ◽  
Female Offspring ◽  
In Utero ◽  
Leptin Resistance ◽  
Metabolic Phenotype ◽  
Postnatal Life ◽  
Chronic Hypertension ◽  
Female Mice ◽  
Reproductive Axis ◽  
Adverse Pregnancy

Preeclampsia (PE) is a devastating disorder of pregnancy that classically presents with maternal hypertension and proteinuria after 20 wk of gestation. In addition to being a leading cause of maternal and fetal morbidity/mortality, epidemiological and prospective studies have revealed long-term consequences for both the mother and baby of preeclamptic pregnancies, including chronic hypertension as well as other cardiovascular diseases and metabolic derangements. To better understand the effect of in utero exposure of PE on offspring, we utilized the BPH/5 mouse, a spontaneous model of the maternal and fetal PE syndrome. We hypothesized that young BPH/5 offspring would have altered metabolic and cardiovascular phenotypes. Indeed, BPH/5 growth-restricted offspring showed excess catch-up growth by early adulthood due to hyperphagia and increased white adipose tissue (WAT) accumulation, with inflammation markers isolated to the reproductive WAT depot only. Both excessive WAT accumulation and the inflammatory WAT phenotype were corrected by pair-feeding young BPH/5 female mice. We also found that young BPH/5 female mice showed evidence of leptin resistance. Indeed, chronic hyperleptinemia has been shown to characterize other rodent models of PE; however, the maternal metabolic profile before pregnancy has not been fully understood. Furthermore, we found that these mice show signs of cardiovascular anomalies (hypertension and cardiomegaly) and altered signaling within the reproductive axis in early life. Future studies will involve challenging the physiological metabolic state of BPH/5 mice through pair-feeding to reduce WAT before pregnancy and determining its causal role in adverse pregnancy outcomes.

scholarly journals Maternal Vitamin D Deficiency Programs Reproductive Dysfunction in Female Mice Offspring Through Adverse Effects on the Neuroendocrine Axis

Endocrinology ◽  
2016 ◽  
Vol 157 (4) ◽  
pp. 1535-1545 ◽  
Author(s):  
Cari Nicholas ◽  
Joseph Davis ◽  
Thomas Fisher ◽  
Thalia Segal ◽  
Marilena Petti ◽  
...  
Keyword(s):  
Vitamin D ◽  
Adverse Effects ◽  
Female Offspring ◽  
In Utero ◽  
Reproductive Physiology ◽  
Gonadal Steroid ◽  
Reproductive Dysfunction ◽  
Control Female ◽  
Female Mice ◽  
Significant Difference

Abstract Vitamin D (VitD) deficiency affects more than 1 billion people worldwide with a higher prevalence in reproductive-aged women and children. The physiological effects of maternal VitD deficiency on the reproductive health of the offspring has not been studied. To determine whether maternal VitD deficiency affects reproductive physiology in female offspring, we monitored the reproductive physiology of C57BL/6J female offspring exposed to diet-induced maternal VitD deficiency at three specific developmental stages: 1) in utero, 2) preweaning, or 3) in utero and preweaning. We hypothesized that exposure to maternal VitD deficiency disrupts reproductive function in exposed female offspring. To test this hypothesis, we assessed vaginal opening and cytology and ovary and pituitary function as well as gonadotropin and gonadal steroid levels in female offspring. The in utero, preweaning, and in utero and preweaning VitD deficiency did not affect puberty. However, all female mice exposed to maternal VitD deficiency developed prolonged and irregular estrous cycles characterized by oligoovulation and extended periods of diestrus. Despite similar gonadal steroid levels and GnRH neuron density, females exposed to maternal VitD deficiency released less LH on the evening of proestrus. When compared with control female offspring, there was no significant difference in the ability of females exposed to maternal VitD deficiency to respond robustly to exogenous GnRH peptide or controlled ovarian hyperstimulation. These findings suggest that maternal VitD deficiency programs reproductive dysfunction in adult female offspring through adverse effects on hypothalamic function.

scholarly journals In Utero Exposure to Simulated Complex Urban Air Pollution Disturbs Intestinal Suckling-to-Weaning Transition in Mice

2021 ◽  
Author(s):  
Eva Guilloteau ◽  
Patrice COLL ◽  
Zhuyi LU ◽  
Madjid DJOUINA ◽  
Mathieu CAZAUNAU ◽  
...  
Keyword(s):  
Air Pollution ◽  
Diversity Index ◽  
Urban Air Pollution ◽  
Female Offspring ◽  
In Utero ◽  
Urban Air ◽  
Female Mice ◽  
Junction Protein ◽  
Pregnant Mice ◽  
Pollution Event

Abstract Background Emerging data indicate that prenatal exposure to air pollution may lead to higher susceptibility to several non-communicable diseases. Limited research has been conducted due to difficulties in modelling realistic air pollution exposure. In this study, pregnant mice were exposed from gestational day 10 to 17 to an atmosphere representative of a 2013 pollution event in Beijing, China. Intestinal homeostasis and microbiota were assessed in both male and female offspring during the suckling-to-weaning transition. Results Sex-specific differences were observed in progeny of gestationally-exposed mice. In utero exposed males exhibited decreased villus and crypt length, vacuolation abnormalities, and lower levels of tight junction protein ZO-1 in ileum. They showed an upregulation of absorptive cell markers and a downregulation of neonatal markers in colon. Cecum of in utero exposed male mice also presented a deeply unbalanced inflammatory pattern. By contrast, in utero exposed female mice displayed less severe intestinal alterations, but included dysregulated expression of Lgr5 in colon, Tjp1 in cecum, and Epcam, Car2 and Sis in ileum. Moreover, exposed female mice showed dysbiosis characterized by a decreased weighted UniFrac β-diversity index, a higher abundance of Bacteroidales and Coriobacteriales orders, and a reduced Firmicutes/Bacteroidetes ratio. Conclusion Prenatal realistic modelling of an urban air pollution event induced sex-specific precocious alterations of structural and immune intestinal development in mice.

scholarly journals GENDER-SPECIFIC INFLUENCE OF Aу MUTATION ON PROGENY METABOLIC PHENOTYPE, FETAL GROWTH AND PLACENTAL GENE EXPRESSION IN MICE

2018 ◽  
Vol 22 (4) ◽  
pp. 406-414 ◽  
Author(s):  
E. N. Makarova ◽  
E. I. Denisova ◽  
V. V. Kozhevnikova ◽  
A. E. Kuleshova
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Female Offspring ◽  
The Body ◽  
Metabolic Phenotype ◽  
Postnatal Life ◽  
Standard Diet ◽  
Mrna Levels ◽  
Male And Female ◽  
Gender Specific

Obesity during pregnancy increases the risk of obesity in offspring. To correct the offspring development in obese mothers, it is necessary to reveal the molecular mechanisms that mediate the influence of the maternal environment on the offspring ontogenesis. Leptin levels increase with obesity. In C57Bl mice, the Ау mutation is associated with elevated blood levels of leptin in pregnant females and exerts a gender-specific effect on the metabolic phenotype of mature offspring. Aim: to study the influence of Ау mutation on sensitivity to diet-induced obesity in male and female offspring, on fetal and placental weight and on the expression of genes in the placentas of the fetuses of different sexes. Body weight and food intake on a standard and an obesogenic diet, fetal and placental weights on pregnancy days 13 and 18, and gene expression of glucose transporters (GLUT1, GLUT3), neutral amino acid transporters (SNAT1, SNAT2, SNAT4), insulin-like growth factor 2 IGF2 and its receptor IGF2R were measured in male and female offspring of и ɑ/ɑ (control) and Ау/ɑ mothers. Ay mutation influenced the body weight only in male offspring, which consumed a standard diet, and did not influence obesity development in both male and female offspring. The weight of fetuses and placentas in Ау/ɑ as compared to ɑ/ɑ  females was reduced on day 13 of pregnancy and was not different on day 18. On day 13 of pregnancy, the mRNA levels of the examined genes did not differ in placentas of male and female fetuses in ɑ/ɑ  females. In Ау/ɑ females, the gene expression of GLUT1, GLUT3, SNAT1 and SNAT4 was reduced in female placentas compared to male placentas. The results suggest that the sex-specific transcription response of placentas to elevated leptin levels in pregnant Ау/ɑ females can mediate the gender-specific impact of Ау mutation on the offspring metabolism in postnatal life.

Impact of paternal cholestasis on the metabolic phenotype of female offspring

2016 ◽  
Author(s):  
Vanessa Pataia ◽  
Georgia Papacleovoulou ◽  
Lucilla Poston ◽  
Catherine Williamson
Keyword(s):  
Female Offspring ◽  
Metabolic Phenotype

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

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Meng Zuo ◽  
Guotao Liao ◽  
Wenqian Zhang ◽  
Dan Xu ◽  
Juan Lu ◽  
...  
Keyword(s):  
Adult Female ◽  
Early Pregnancy ◽  
Testosterone Level ◽  
Metabolic Disorders ◽  
Serum Testosterone ◽  
Female Offspring ◽  
Metabolic Phenotype ◽  
Serum Testosterone Level ◽  
The Metabolic Syndrome ◽  
Pcos Group

Abstract 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.

scholarly journals Prognostic value of different maternal obesity phenotypes in predicting offspring obesity in a family-based cohort study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sara Jalali-Farahani ◽  
Parisa Amiri ◽  
Bita Lashkari ◽  
Leila Cheraghi ◽  
Farhad Hosseinpanah ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Childhood Obesity ◽  
Maternal Obesity ◽  
Female Offspring ◽  
Normal Weight ◽  
Metabolic Status ◽  
World Health ◽  
Metabolic Phenotype ◽  
Maternal Body Mass Index ◽  
Obesity In Children

Abstract Background Parental weight is studied as an important determinant of childhood obesity; however, obesity-related metabolic abnormalities have been less considered as determinants of childhood obesity. This study aimed to investigate the association between maternal obesity phenotypes and incidence of obesity in their offspring. Methods This longitudinal study was conducted within the framework of the Tehran Lipid and Glucose Study. A total of 2151 non-obese children who had complete parental information were followed for incidence of obesity over a mean of 148.7 ± 34.7 months. Obesity in children was defined using the World Health Organization criteria. Maternal body mass index (BMI) was classified into three categories: normal weight, overweight and obese. Dysmetabolic status was considered as having metabolic syndrome or diabetes. Metabolic syndrome and diabetes were defined according to the Joint Interim Statement and American diabetes association criteria, respectively. Considering maternal BMI categories and metabolic status, six obesity phenotypes were defined as followed: 1) normal weight and normal metabolic status, 2) overweight and normal metabolic status, 3) obese and normal metabolic status, 4) normal weight and dysmetabolic status, 5) overweight and dysmetabolic status, and 6) obese and dysmetabolic status. The association between maternal obesity phenotypes and incidence of obesity in children was studied using Cox proportional regression hazard model. Results In male offspring, the risk of incidence of obesity significantly increased in those with maternal obesity phenotypes including overweight/normal metabolic: 1.75(95% CI: 1.10–2.79), obese/normal metabolic: 2.60(95%CI: 1.51–4.48), overweight/dysmetabolic: 2.34(95%CI: 1.35–4.03) and obese/dysmetabolic: 3.21(95%CI: 1.94–5.03) compared to the normal weight/normal metabolic phenotype. Similarly, in girls, the risk of incidence of obesity significantly increased in offspring with maternal obesity phenotypes including overweight/normal metabolic: 2.39(95%CI: 1.46–3.90), obese/normal metabolic: 3.55(95%CI: 1.94–6.46), overweight/dysmetabolic: 1.92(95%CI: 1.04–3.52) and obese/dysmetabolic: 3.89(95%CI: 2.28–6.64) compared to normal weight/normal metabolic phenotype. However, maternal normal weight/dysmetabolic phenotype did not significantly change the risk of obesity in both male and female offspring. Conclusion Except for normal weight/dysmetabolic phenotype, all maternal obesity phenotypes had significant prognostic values for incidence of offspring obesity with the highest risk for obese/dysmetabolic phenotype. This study provides valuable findings for identifying the first line target groups for planning interventions to prevent childhood obesity.

THE 'EARLY ANDROGEN SYNDROME' IN THE GUINEA-PIG

1971 ◽  
Vol 49 (2) ◽  
pp. 277-291 ◽  
Author(s):  
K. BROWN-GRANT ◽  
M. R. SHERWOOD
Keyword(s):  
Guinea Pig ◽  
External Genitalia ◽  
Female Offspring ◽  
Postnatal Life ◽  
Vaginal Opening ◽  
Vaginal Smears ◽  
Short Period ◽  
Luteal Tissue ◽  
Pituitary Glands ◽  
Androgenic Steroids

SUMMARY When testosterone propionate was administered to pregnant guinea-pigs over a short period (days 33–37) of gestation a high proportion of the female offspring exhibited a characteristic syndrome. The time of the first vaginal opening was delayed and its duration reduced. Subsequent periods of opening were fairly regular in occurrence but were shorter in duration than in normal animals; the 'cycle' length was usually slightly longer. Continuous vaginal opening was not observed but during the periods of opening, vaginal smears containing many cornified cells and no leucocytes were obtained. During the periods of vaginal opening no lordosis response to manual stimulation could be elicited nor did the animals mate when run with males. The increase in body weight was normal up to about 150 days of age and slightly, but not significantly, less than that of controls between 150 and 200 days of postnatal life. As adults some masculinization of the external genitalia was observed. At autopsy the weights of the uteri, ovaries, adrenal and anterior pituitary glands were much greater than those of control animals at any stage of the cycle. Histological examination showed that the ovaries contained many antral follicles but no luteal tissue. Enlargement of the glands and metaplastic changes in the epithelium were observed in the uteri. The pituitaries showed an excess of cells containing large, densely packed eosinophilic granules. This early androgen syndrome is compared with that produced by hypothalamic lesions in the guinea-pig and with the changes produced in other species by the administration of androgenic steroids during prenatal or early postnatal life.

Placental insufficiency induces a sexually dimorphic response in the expression of cardiac growth and metabolic signalling molecules upon exposure to a postnatal western diet in guinea pigs

2021 ◽  
pp. 1-13
Author(s):  
Jack R.T. Darby ◽  
Jacky Chiu ◽  
Timothy R.H. Regnault ◽  
Janna L. Morrison
Keyword(s):  
Birth Weight ◽  
Mrna Expression ◽  
Female Offspring ◽  
Postnatal Life ◽  
Sexually Dimorphic ◽  
Fibrotic Response ◽  
Cardiac Growth ◽  
Signalling Molecules ◽  
Secondary Insult ◽  
Obesogenic Diet

Abstract There is a strong relationship between low birth weight (LBW) and an increased risk of developing cardiovascular disease (CVD). In postnatal life, LBW offspring are becoming more commonly exposed to the additional independent CVD risk factors, such as an obesogenic diet. However, how an already detrimentally programmed LBW myocardium responds to a secondary insult, such as an obesogenic diet (western diet; WD), during postnatal life is ill defined. Herein, we aimed to determine in a pre-clinical guinea pig model of CVD, both the independent and interactive effects of LBW and a postnatal WD on the molecular pathways that regulate cardiac growth and metabolism. Uterine artery ablation was used to induce placental insufficiency (PI) in pregnant guinea pigs to generate LBW offspring. Normal birth weight (NBW) and LBW offspring were weaned onto either a Control diet or WD. At ˜145 days after birth (young adulthood), male and female offspring were humanely killed, the heart weighed and left ventricle tissue collected. The mRNA expression of signalling molecules involved in a pathological hypertrophic and fibrotic response was increased in the myocardium of LBW male, but not female offspring, fed a WD as was the mRNA expression of transcription factors involved in fatty acid oxidation. The mRNA expression of glucose transporters was downregulated by LBW and WD in male, but not female hearts. This study has highlighted a sexually dimorphic cardiac pathological hypertrophic and fibrotic response to the secondary insult of postnatal WD consumption in LBW offspring.

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