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.

Abstract 67: Metabolic Programming Regulates Proliferation and Binucleation of Postnatal Cardiomyocytes

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Daniela Liccardo ◽  
Ryan LaCanna ◽  
Ying Tian
Keyword(s):  
Cell Cycle ◽  
Natriuretic Peptides ◽  
Metabolic Programming ◽  
Postnatal Life ◽  
Mouse Heart ◽  
Cardiomyocyte Proliferation ◽  
Beta Oxidation ◽  
Neonatal Cardiomyocytes ◽  
Short Period

In contrast to adult, neonatal cardiomyocytes are able to proliferate and lose this capacity soon after birth when they withdraw from the cell cycle, become binucleated and differentiate. The arrest of cardiomyocytes cell cycle can be reversible for a short period, conferring the neonatal heart a regenerative potential within the first week of postnatal life. In the timeframe surrounding birth, heart maturation is also characterized by a change in energy metabolism, switching from glycolysis to beta-oxidation. However little is known about how metabolic programming in postnatal cardiomyocytes regulates their ability to proliferate, become binucleated and differentiate. In this study, we show that blocking beta-oxidation in mouse neonatal cardiomyocytes with etomoxir treatment promotes glycolysis and cell cycle re-entry, while increasing fatty acid beta-oxidation but reducing glycolysis leads to a decrease of the number of proliferating cardiomyocytes. In neonatal mice our data demonstrate that cardiomyocytes undergo binucleation and differentiation during the first week after birth and this process is correlated with the upregulation of the natriuretic peptides, ANP and BNP expression. Notably, in the postnatal mouse heart, beta-oxidation blockade through in vivo etomoxir injections, increases ventricular cardiomyocytes number, decreases natriuretic peptides expression and reduces the conversion of cardiomyocytes from a mononucleated to a binucleated phenotype. These findings highlight the importance of metabolic programming in regulating cardiomyocyte proliferation and suggest a potential therapeutic target for heart regeneration by modulating energy metabolic programming.

scholarly journals Prenatal Glucocorticoid Exposure Results in Changes in Gene Transcription and DNA Methylation in the Female Juvenile Guinea Pig Hippocampus Across Three Generations

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Andrea Constantinof ◽  
Lisa Boureau ◽  
Vasilis G. Moisiadis ◽  
Alisa Kostaki ◽  
Moshe Szyf ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Guinea Pig ◽  
Gene Transcription ◽  
Fetal Brain ◽  
Neonatal Morbidity ◽  
Fetal Lung ◽  
Female Offspring ◽  
Transgenerational Transmission ◽  
Paternal Lineage ◽  
Three Generations

AbstractSynthetic glucocorticoids (sGC) are administered to women at risk for pre-term delivery, to mature the fetal lung and decrease neonatal morbidity. sGC also profoundly affect the fetal brain. The hippocampus expresses high levels of glucocorticoid (GR) and mineralocorticoid receptor (MR), and its development is affected by elevated fetal glucocorticoid levels. Antenatal sGC results in neuroendocrine and behavioral changes that persist in three generations of female guinea pig offspring of the paternal lineage. We hypothesized that antenatal sGC results in transgenerational changes in gene expression that correlate with changes in DNA methylation. We used RNASeq and capture probe bisulfite sequencing to investigate the transcriptomic and epigenomic effects of antenatal sGC exposure in the hippocampus of three generations of juvenile female offspring from the paternal lineage. Antenatal sGC exposure (F0 pregnancy) resulted in generation-specific changes in hippocampal gene transcription and DNA methylation. Significant changes in individual CpG methylation occurred in RNApol II binding regions of small non-coding RNA (snRNA) genes, which implicates alternative splicing as a mechanism involved in transgenerational transmission of the effects of antenatal sGC. This study provides novel perspectives on the mechanisms involved in transgenerational transmission and highlights the importance of human studies to determine the longer-term effects of antenatal sGC on hippocampal-related function.

Nutritional challenges during development induce sex-specific changes in glucose homeostasis in the adult sheep

2007 ◽  
Vol 292 (1) ◽  
pp. E32-E39 ◽  
Author(s):  
Kirsten R. Poore ◽  
Jane K. Cleal ◽  
James P. Newman ◽  
Julian P. Boullin ◽  
David E. Noakes ◽  
...  
Keyword(s):  
Body Composition ◽  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
Area Under The Curve ◽  
Postnatal Growth ◽  
Female Offspring ◽  
Postnatal Life ◽  
Intravenous Glucose ◽  
Ad Libitum ◽  
Early Postnatal Life

The early-life environment has implications for risk of adult-onset diseases, such as glucose intolerance, insulin insensitivity, and obesity, effects that may occur with or without reduced birth weight. We determined the consequences of nutrient restriction in early gestation and early postnatal life and their interactions on postnatal growth, body composition, and glucose handling. Ewes received 100% (C, n = 39) or 50% nutritional requirements (U, n = 41) from 1 to 31 days gestation and 100% thereafter. Male and female offspring (singleton/twin) from C and U ewes were then fed either ad libitum (CC n = 22, UC n = 19) or to reduce body weight to 85% of target from 12 to 25 wk of age (CU n = 17, UU n = 22) and ad libitum thereafter. At 1.5 and 2.5 yr, glucose handling was determined by area under the curve (AUC) for glucose and insulin concentrations following intravenous glucose (0.5 g/kg body wt). Insulin sensitivity was determined at 2.5 yr following intravenous insulin (0.5 IU/kg). In females, postnatal undernutrition reduced ( P < 0.05) glucose AUC at both ages, regardless of prenatal nutrition. Postnatal undernutrition did not affect insulin secretion in females but enhanced insulin-induced glucose disappearance in singletons. Poor early postnatal growth was associated with increased fat in females. In males, glucose tolerance was unaffected by undernutrition despite changes in insulin AUC dependent on age, treatment, and single/twin birth. Nutrition in early postnatal life has long-lasting, sex-specific effects on glucose handling in sheep, likely due, in females, to enhanced insulin sensitivity. Improved glucose utilization may aid weight recovery but have negative implications for glucose homeostasis and body composition over the longer term.

scholarly journals Maternal High-Fat Diet and Offspring Expression Levels of Vitamin K–Dependent Proteins

Endocrinology ◽  
2014 ◽  
Vol 155 (12) ◽  
pp. 4749-4761 ◽  
Author(s):  
S. A. Lanham ◽  
F. R. Cagampang ◽  
R. O. C. Oreffo
Keyword(s):  
Vitamin K ◽  
High Fat Diet ◽  
Maternal Nutrition ◽  
Vascular Tissue ◽  
Bone Structure ◽  
Female Offspring ◽  
Matrix Gla Protein ◽  
Postnatal Life ◽  
High Fat ◽  
Expression Levels

Studies suggest that bone growth and development and susceptibility to vascular disease in later life are influenced by maternal nutrition during intrauterine and early postnatal life. There is evidence for a role of vitamin K–dependent proteins (VKDPs) including osteocalcin, matrix Gla protein, periostin, and growth-arrest specific– protein 6, in both bone and vascular development. We have examined whether there are alterations in these VKDPs in bone and vascular tissue from offspring of mothers subjected to a nutritional challenge: a high-fat diet during pregnancy and postnatally, using 6-week-old mouse offspring. Bone site–specific and sex-specific differences across femoral and vertebral bone in male and female offspring were observed. Overall a high-fat maternal diet and offspring diet exacerbated the bone changes observed. Sex-specific differences and tissue-specific differences were observed in VKDP levels in aorta tissue from high-fat diet–fed female offspring from high-fat diet–fed mothers displaying increased levels of Gas6 and Ggcx compared with those of female controls. In contrast, differences were seen in VKDP levels in femoral bone of female offspring with lower expression levels of Mgp in offspring of mothers fed a high-fat diet compared with those of controls. We observed a significant correlation in Mgp expression levels within the femur to measures of bone structure of the femur and vertebra, particularly in the male offspring cohort. In summary, the current study has highlighted the importance of maternal nutrition on offspring bone development and the correlation of VKDPs to bone structure.

Studies of new short-period method for delayed contact hypersensitivity assay in the guinea pig

1993 ◽  
Vol 28 (4) ◽  
pp. 235-242 ◽  
Author(s):  
Ryuichi Kashima ◽  
Yumiko Oyake ◽  
Joskin Okaua ◽  
Yuzo Ikeda
Keyword(s):  
Guinea Pig ◽  
Contact Hypersensitivity ◽  
Short Period

Uptake and retention of3H-estradiol by gonadotrophs and lactotrophs in the pituitary glands of the guinea pig, hamster and gerbil

1987 ◽  
Vol 248 (1) ◽  
pp. 75-78 ◽  
Author(s):  
Haruo Nogami ◽  
Damon C. Herbert ◽  
William B. Winborn ◽  
Frank J. Weaker ◽  
Peter J. Sheridan
Keyword(s):  
Guinea Pig ◽  
Pituitary Glands

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.

FACTORS DETERMINING CESSATION OF CORPUS LUTEUM FUNCTION; THE POSSIBLE ROLE OF OESTRADIOL AND PROGESTERONE

1964 ◽  
Vol 45 (4_Suppl) ◽  
pp. S125-S132 ◽  
Author(s):  
S. E. de Jongh ◽  
O. L. Wolthuis
Keyword(s):  
Corpus Luteum ◽  
Fixed Dose ◽  
List Type ◽  
Vaginal Opening ◽  
Vaginal Smears ◽  
Uterine Endometrium ◽  
Marked Inhibition ◽  
Oestradiol Benzoate ◽  
Sparing Effect

ABSTRACT The role of oestrogen and progesterone utilization by the uterus was investigated with regard to the mechanism of cessation of corpus luteum function. After the administration of oestradiol benzoate with or without progesterone in various combinations to spayed, spayed-hysterectomized, or spayed traumatized rats it was found that: there were no percentage differences in the oestrogenic effects in the vaginal smears of spayed or spayed-hysterectomized rats after the administration of oestradiol benzoate alone. After treatment with combinations of oestradiol and progesterone, the oestrogenic effects were inhibited in spayed-hysterectomized animals as compared with similarly treated spayed controls. A still more marked inhibition was obtained after traumatizing the uterine endometrium. Increasing doses of progesterone in combination with a fixed dose of oestradiol benzoate progressively delayed vaginal opening. It is concluded that the uterus does not utilize any measurable amounts of oestrogen, but that, on the other hand, it does utilize considerable quantities of progesterone. Traumatization of the uterus may have a similar progesterone-sparing effect. The findings are discussed against the background of factors which determine cessation of corpus luteum function, while it is suggested that progesterone may be an important factor accounting for the effects of hysterectomy.

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