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.

scholarly journals A next-generation sequencing study on mechanisms by which restraint and social instability stresses of male mice alter offspring anxiety-like behavior

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qiao-Qiao Kong ◽  
Xiao-Dan Tian ◽  
Jia Wang ◽  
Hong-Jie Yuan ◽  
Shu-Fen Ning ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Next Generation Sequencing ◽  
Female Offspring ◽  
Next Generation ◽  
Transgenerational Transmission ◽  
Social Instability ◽  
Sperm Dna ◽  
And Control ◽  
Generation Sequencing ◽  
Sperm Dna Methylation

AbstractPathophysiological mechanisms for depression/anxiety are largely unknown. Evidence for transgenerational transmission of acquired epigenetic marks remains limited. We bred unstressed (US) female mice with adolescently restraint-stressed (RS), social instability-stressed (SI) or US males to produce RS, SI and control F1 offspring, respectively. Compared to controls, while paternal RS decreased anxiety-like behavior (ALB) in both female and male offspring, paternal SI increased ALB only in female offspring. Next-generation sequencing and bioinformatics using RS and SI female offspring identified 5 candidate anxiety-transmitting (CAT) genes; each showed a consistent pattern of DNA methylation from F0 spermatozoa through F1 blastocysts to fetal and adult hippocampi. Further analyses validated 4 CAT genes, demonstrated that paternal SI caused ALB differences between male and female offspring through modifying the CAT genes, and indicated a strong correlation between inflammation and ALB pathogenesis and an important function for intronic DNA methylation in regulating ALB-related genes. In conclusion, this study identified important CAT genes and suggested the possibility that stresses on males might alter offspring’s ALB by modifying sperm DNA methylation.

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.

Impact of depression and stress on placental DNA methylation in ethnically diverse pregnant women

Epigenomics ◽  
2021 ◽  
Author(s):  
Markos Tesfaye ◽  
Suvo Chatterjee ◽  
Xuehuo Zeng ◽  
Paule Joseph ◽  
Fasil Tekola-Ayele
Keyword(s):  
Dna Methylation ◽  
Fetal Brain ◽  
Ethnically Diverse ◽  
Antenatal Depression ◽  
Epigenetic Changes ◽  
Clinical Trial Registration ◽  
False Discovery ◽  
Genome Wide ◽  
Neuropsychiatric Diseases ◽  
Registration Number

Aim: To investigate the association between placental genome-wide methylation at birth and antenatal depression and stress during pregnancy. Methods: We examined the association between placental genome-wide DNA methylation (n = 301) and maternal depression and stress assessed at six gestation periods during pregnancy. Correlation between DNA methylation at the significantly associated CpGs and expression of nearby genes in the placenta was tested. Results: Depression and stress were associated with methylation of 16 CpGs and two CpGs, respectively, at a 5% false discovery rate. Methylation levels at two of the CpGs associated with depression were significantly associated with expression of ADAM23 and CTDP1, genes implicated in neurodevelopment and neuropsychiatric diseases. Conclusion: Placental epigenetic changes linked to antenatal depression suggest potential fetal brain programming. Clinical trial registration number: NCT00912132 (ClinicalTrials.gov)

58: Elective delivery with known fetal lung maturity prior to 39 wks is still associated with increased neonatal morbidity

2011 ◽  
Vol 204 (1) ◽  
pp. S33-S34 ◽  
Author(s):  
Yu Ming Victor Fang ◽  
Peter Guirguis ◽  
Adam Borgida ◽  
Deborah Feldman ◽  
Charles Ingardia ◽  
...  
Keyword(s):  
Neonatal Morbidity ◽  
Fetal Lung ◽  
Fetal Lung Maturity ◽  
Elective Delivery ◽  
Lung Maturity

scholarly journals Transgenerational Transmission of Trauma across Three Generations of Alevi Kurds

2021 ◽  
Vol 19 (1) ◽  
pp. 81
Author(s):  
Jan Ilhan Kizilhan ◽  
Michael Noll-Hussong ◽  
Thomas Wenzel
Keyword(s):  
Qualitative Interviews ◽  
Religious Groups ◽  
National Socialist ◽  
Western Turkey ◽  
Transgenerational Transmission ◽  
Traumatic Memories ◽  
Three Generations ◽  
Transmission Of Trauma ◽  
Few Data ◽  
Transgenerational Transmission Of Trauma

Background: Thus far, most researchers on genocide and transgenerational transmissions have focused on the National Socialist Holocaust as the most abhorrent example of this severe human rights violation. Few data have been published on other ethnic or religious groups affected by genocidal actions in this context. Methodology: Using a mixed-method approach integrating qualitative interviews with standardized instruments (SCID and PDS), this study examines how individual and collective trauma have been handed down across three generations in an Alevi Kurd community whose members (have) suffered genocidal perpetrations over a longer time period (a “genocidal environment”). Qualitative, open-ended interviews with members of three generations answering questions yielded information on (a) how their lives are shaped by the genocidal experiences from the previous generation and related victim experiences, (b) how the genocidal events were communicated in family narratives, and (c) coping strategies used. The first generation is the generation which directly suffered the genocidal actions. The second generation consists of children of those parents who survived the genocidal actions. Together with their family (children, partner, relatives), this generation suffered forced displacement. Members of the third generation were born in the diaspora where they also grew up. Results: Participants reported traumatic memories, presented in examples in this publication. The most severe traumatic memories included the Dersim massacre in 1937–1938 in Turkey, with 70,000–80,000 victims killed, and the enforced resettlement in western Turkey. A content analysis revealed that the transgenerational transmission of trauma continued across three generations. SCID and PDS data indicated high rates of distress in all generations. Conclusions: Genocidal environments such as that of the Kurdish Alevis lead to transgenerational transmission mediated by complex factors.

scholarly journals Genome-wide DNA methylation profiles in progression to in situand invasive carcinoma of the breast with impact on gene transcription and prognosis

2014 ◽  
Vol 15 (8) ◽  
Author(s):  
Thomas Fleischer ◽  
Arnoldo Frigessi ◽  
Kevin C Johnson ◽  
Hege Edvardsen ◽  
Nizar Touleimat ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gene Transcription ◽  
Invasive Carcinoma ◽  
Carcinoma Of The Breast ◽  
Genome Wide

Pharmacokinetics of ethanol and its metabolite, acetaldehyde, and fetolethality in the third-trimester pregnant guinea pig for oral administration of acute, multiple-dose ethanol

1986 ◽  
Vol 64 (8) ◽  
pp. 1060-1067 ◽  
Author(s):  
David W. Clarke ◽  
Nancy A. E. Steenaart ◽  
Christopher J. Slack ◽  
James F. Brien
Keyword(s):  
Guinea Pig ◽  
Amniotic Fluid ◽  
Ethanol Concentration ◽  
Fetal Brain ◽  
Maternal Blood ◽  
Time Interval ◽  
Gas Liquid Chromatography ◽  
Fetal Blood ◽  
Third Trimester ◽  
The Third

The pharmacokinetics of ethanol and its metabolite, acetaldehyde, were determined in the third-trimester pregnant guinea pig (56–59 days gestation) for oral intubation of four doses of 1 g ethanol/kg maternal body weight, administered at 1-h intervals. Animals (n = 4–7) were sacrificed at each of selected times during the 26-h study. Ethanol and acetaldehyde concentrations were determined by headspace gas-liquid chromatography. The maternal and fetal blood ethanol concentration–time curves were virtually superimposable, which indicated unimpeded bidirectional placental transfer of ethanol in the matemal–fetal unit. The blood and brain ethanol concentrations were similar in each of the maternal and fetal compartments during the study, which indicated rapid equilibrium distribution of ethanol. There was accumulation of ethanol in the amniotic fluid resulting in higher ethanol concentration compared with maternal and fetal blood during the elimination phase, which indicated that the amniotic fluid may serve as a reservoir for ethanol in utero. Acetaldehyde was measurable in all the biological fluids and tissues at concentrations that were at least 1000-fold less than the respective ethanol concentrations and were variable. There was ethanol-induced fetolethality that was delayed and variable among animals, and was 55% at 23 h. At this time interval, the ethanol concentrations in maternal blood and brain, fetal brain, and amniotic fluid were 35- to 53-fold greater and the acetaldehyde concentrations in maternal blood and fetal brain were four- to five-fold higher in the animals with dead fetuses compared with the guinea pigs with live litters. These data indicated that decreased ethanol elimination from the maternal–fetal unit was related temporally to the fetolethality.

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