Sex- and brain region- specific effects of prenatal stress and lead exposure on permissive and repressive post-translational histone modifications from embryonic development through adulthood

Time-specificity has been well established in numerous experiments in which a teratogenic agent has been shown to cause different malformations when applied at different times in development. These time-specific effects are related to definite stages or events in embryonic development which might be regarded as periods of special susceptibility. Excessive doses tend to obscure time-specificity by causing teratogenic effects at times other than during periods of special susceptibility. Recent experiments have indicated that, irrespective of time, many teratogenic agents seem to produce distinctive patterns of anomalies which differ qualitatively and quantitatively from those caused by other agents. The association of a particular group of malformations with a particular agent may be termed agent-specificity. Agent-specificity is not always readily apparent for reasons such as: a) elimination of certain types of abnormalities by fetal death of affected individuals, b) fluctuations in the pattern resulting from variations in dosage of the agent, c) variable reactions to the same agent in different species or even different strains, and d) varying interests and methods of study on the part of the investigator. When due allowance is made for such variables, distinctive patterns of malformations can often be associated with particular teratogenic agents. Although mechanisms of agent-specificity were not discussed in detail, it was suggested that each agent acts by interfering with a particular metabolic process in a specific way in the differentiating and growing embryo. Such action can be localized, generalized or selectively distributed, depending on the distribution within the embryo of the process concerned.

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Hippocampal Synaptic Stability and Plasticity

Estrogens and Memory ◽

10.1093/oso/9780190645908.003.0007 ◽

2020 ◽

pp. 83-95

Author(s):

Gabriele M. Rune

Keyword(s):

Embryonic Development ◽

Learning And Memory ◽

Brain Region ◽

Long Term Potentiation ◽

Synaptic Potentiation ◽

Term Potentiation ◽

Synapse Density ◽

Hippocampal Cultures ◽

Estradiol Synthesis

Estradiol synthesis depends on the activity of aromatase, the enzyme that specifically and irreversibly converts testosterone to estradiol in steroidogenesis. Aromatase is expressed and is active in the hippocampus, a brain region related to learning and memory. Dynamics of spines and spine synapses, including expression of presynaptic and postsynaptic proteins, are controlled by hippocampus-derived estradiol in female rodents, but not in male rodents. This also holds true for long-term potentiation. Inhibition of aromatase, either pharmacologically or by genetic approaches, results in a decrease in synapse density and synaptic potentiation in female animals and in neonatal hippocampal cultures that originate from females. The consistency of the findings in rodents and in perinatal primary hippocampal cultures points to sex-specific differentiation processes during embryonic development, which underlie sex-dependent differences in neurosteroid action in the hippocampus.

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Prenatal stress, gestational age and secondary sex ratio: the sex-specific effects of exposure to a natural disaster in early pregnancy

Human Reproduction ◽

10.1093/humrep/der390 ◽

2011 ◽

Vol 27 (2) ◽

pp. 558-567 ◽

Cited By ~ 77

Author(s):

Florencia Torche ◽

Karine Kleinhaus

Keyword(s):

Sex Ratio ◽

Natural Disaster ◽

Early Pregnancy ◽

Gestational Age ◽

Prenatal Stress ◽

Specific Effects ◽

Secondary Sex Ratio

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ConditionalKIAA1549:BRAFmice reveal brain region- and cell type-specific effects

genesis ◽

10.1002/dvg.22415 ◽

2013 ◽

Vol 51 (10) ◽

pp. 708-716 ◽

Cited By ~ 9

Author(s):

Aparna Kaul ◽

Yi-Hsien Chen ◽

Ryan J. Emnett ◽

Scott M. Gianino ◽

David H. Gutmann

Keyword(s):

Brain Region ◽

Cell Type ◽

Specific Effects ◽

Cell Type Specific

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Sex-Specific Effects of Prenatal Stress on Bdnf Expression in Response to an Acute Challenge in Rats: a Role for Gadd45β

Molecular Neurobiology ◽

10.1007/s12035-015-9569-4 ◽

2015 ◽

Vol 53 (10) ◽

pp. 7037-7047 ◽

Cited By ~ 18

Author(s):

A. Luoni ◽

A. Berry ◽

C. Raggi ◽

V. Bellisario ◽

F. Cirulli ◽

...

Keyword(s):

Prenatal Stress ◽

Bdnf Expression ◽

Specific Effects ◽

Acute Challenge

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m6a Methylation Inhibition by Cycloleucine Impaired Porcine Oocyte Meiosis and Early Embryonic Development via Remodeling Histone Modifications and Altering Metabolism Related Gene Expression in Blastocysts

10.21203/rs.3.rs-104068/v1 ◽

2020 ◽

Author(s):

Meng Zhang ◽

Sheng Zhang ◽

Yanhui Zhai ◽

Yu Han ◽

Rong Huang ◽

...

Keyword(s):

Gene Expression ◽

Embryonic Development ◽

Histone Modifications ◽

Early Embryo ◽

Early Embryonic Development ◽

Related Gene ◽

Cell Stage ◽

Oocyte Meiosis ◽

Porcine Oocyte ◽

Parthenogenetic Embryos

Abstract BackgroundOocytes maturation and early embryo development were regulated precisely by a series of factors at transcriptional and posttranslational levels. N6-methyladenosine (m6A) is the most prevalent modification in mRNA as a crucial regulator in RNA metabolism and gene regulation. However, the role of m6A on porcine oocyte maturation and early embryogenesis is largely unknown. ResultsHere, we found that oocytes treated with cycloleucine (CL), an inhibitor of m6A, could impair cumulus expansion, elevate mitochondrial reactive oxygen species (ROS) concentration and decreased oocytes maturation which partially caused by disturbed spindle organization and chromosomes alignment. Moreover, our results indicated that the CL treated parthenogenetic embryos arrested at 4-cell stage and showed worse blastocyst quality. CL treatment not only decreased the methylation levels of nucleic acid, H3K4me3 and H3K9me3, while increased the acetylation level of H4K16 during parthenogenetic embryos development in pigs. Furthermore, single cell RNA-seq (scRNA-seq) analysis indicated that CL treatment dramatically elevated the expression of metabolism-related (SLC16A1 and MAIG3 etc.) and maternal related (BTG4, WEE2 and BMP15 etc.) genes at blastocyst stage. ConclusionsTaken together, we found that m6A methylation inhibition by CL impaired porcine oocyte meiosis and early embryonic development via remodeling histone modifications and altering metabolism related gene expression in blastocysts.

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