Intergenerational response of steroidogenesis-related genes to maternal malnutrition

2019 ◽  
Vol 10 (5) ◽  
pp. 587-594
Author(s):  
Abdel Halim Harrath ◽  
Abdulkarem Alrezaki ◽  
Saleh H. Alwasel ◽  
Abdelhabib Semlali
Keyword(s):  
Gene Expression ◽  
Reproductive Success ◽  
Adaptive Response ◽  
Food Restriction ◽  
Reproductive Capacity ◽  
Maternal Malnutrition ◽  
Pubertal Onset ◽  
Ovarian Aging ◽  
Premature Ovarian Aging ◽  
Predictive Adaptive Response

AbstractWe sought to examine whether rat maternal food restriction (MFR) affects the expression of steroidogenesis-related genes Cyp19, Cyp17a1, Insl3 and Gdf-9 in the ovaries of offspring from the first (FRG1) and second (FRG2) generations at pre-pubertal age (week 4) and during adulthood (week 8). At week 4, MFR significantly increased the expression of RNAs for all analyzed genes in both FRG1 and FRG2 females, which may indicate that MFR affects the onset of the reproductive lifespan, by inducing early pubertal onset. At week 8, the Cyp19 gene was still upregulated in MRF-subjected animals (Cyp19: P=0.0049 and P=0.0508 in FRG1 and FRG2, respectively), but MFR induced a significant decrease in Cyp17 and Gdf-9 gene expression in the offspring of both FRG1 and FRG2 females when compared with the controls (Cyp17: P=0.0018 and P=0.0016, respectively; Gdf-9: P=0.0047 and P=0.0023, respectively). This suggests that females at week 8, which should normally be in their optimal reproductive capacity, experience premature ovarian aging. At week 4, the activation of Cyp19 and Cyp17 was higher in the FRG1 ovaries than in the FRG2 ovaries, whereas the extent of Insl3 and Gdf-9 activation was lower in the FRG1 ovaries. This may indicate that FRG2 females were more vulnerable to MFR than their mothers (FRG1) and grandmothers, which is consistent with the ‘predictive adaptive response’ hypothesis. Our findings reveal that MFR may induce intergenerational ovarian changes as an adaptive response to ensure reproductive success before death.

scholarly journals A ‘phenotypic hangover’ – the predictive adaptive response and multigenerational effects of altered nutrition on the transcriptome of Drosophila melanogaster

2017 ◽  
Author(s):  
Amy J. Osborne ◽  
Peter K. Dearden
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Adaptive Response ◽  
Communicable Disease ◽  
Later Life ◽  
Standard Diet ◽  
Expression Of Genes ◽  
Postnatal Environment ◽  
Predictive Adaptive Response ◽  
Epigenetic Processes

AbstractThe Developmental Origins of Health and Disease (DOHaD) hypothesis predicts that early-life environmental exposures can be detrimental to later-life health, and that mismatch between the pre- and postnatal environment may contribute to the growing non-communicable disease (NCD) epidemic. Within this is an increasingly recognised role for epigenetic mechanisms; epigenetic modifications can be influenced by, e.g., nutrition, and can alter gene expression in mothers and offspring. Currently, there are no whole-genome transcriptional studies of response to nutritional alteration. Thus, we sought to explore how nutrition affects the expression of genes involved in epigenetic processes in Drosophila melanogaster. We manipulated Drosophila food macronutrient composition at the F0 generation, mismatched F1 offspring back to a standard diet, and analysed the transcriptome of the F0 – F3 generations by RNA-sequencing. At F0, the altered (high protein, low carbohydrate, HPLC) diet increased expression of genes involved in epigenetic processes, with coordinated downregulation of genes involved in immunity, neurotransmission and neurodevelopment, oxidative stress and metabolism. Upon reversion to standard nutrition, mismatched F1 and F2 generations displayed multigenerational inheritance of altered gene expression. By the F3 generation, gene expression had reverted to F0 (matched) levels. These nutritionally-induced gene expression changes demonstrate that dietary alteration can upregulate epigenetic genes, which may influence the expression of genes with broad biological functions. Further, the multigenerational inheritance of the gene expression changes in F1 and F2 mismatched generations suggests a predictive adaptive response (PAR) to maternal nutrition. Our findings may help to understand the interaction between maternal diet and future offspring health, and have direct implications for the current NCD epidemic.

scholarly journals Mechanisms of short-term and long-term adaptation

2020 ◽  
pp. 77-86
Author(s):  
Н.Б. Панкова
Keyword(s):  
Gene Expression ◽  
Epigenetic Regulation ◽  
Adaptive Response ◽  
Educational Environment ◽  
Stress Factors ◽  
Short Term ◽  
Functional Reserve ◽  
Short Term Adaptation ◽  
Expression Program

В лекции рассмотрены общие представления об адаптации, основанные на классических работах Г. Селье, Ф.З. Меерсона, Н.А. Агаджаняна, а также особенности адаптивного ответа развивающегося организма. Рассмотрены механизмы срочной адаптации как мобилизации функциональных резервов организма. В качестве одного из механизмов долговременной адаптации представлена эпигенетическая регуляция, которая позволяет выбрать и реализовать программу экспрессии генов - в соответствии с этапом онтогенетического развития, или средовым окружением. В качестве ещё одного механизма долговременной адаптации рассмотрено воздействие на генетический материал. Приведены примеры формирования адаптивного ответа организма на физико-химические и климатогеографические стрессорные факторы. Отдельно проанализированы механизмы адаптивного ответа организма детей на факторы образовательной среды. The lecture addresses general ideas about adaptation based on classic studies by H. Selye, F.Z. Meerson, and N.A. Agadzhanyan and features of the adaptive response in a developing body. Mobilization of the functional reserve is considered as a mechanism of short-term adaptation. Epigenetic regulation is presented as one of mechanisms for long-term adaptation, which allows selecting and implementing a gene expression program consistent with the stage of ontogenetic development or the environment. Another mechanism of long-term adaptation is influence on the genome. The lecture provides examples of adaptation to physicochemical and climatic geographical stress factors. Mechanisms of the adaptive response to factors of the educational environment in children are analyzed separately.

scholarly journals Pcsk6 mutant mice exhibit progressive loss of ovarian function, altered gene expression, and formation of ovarian pathology

Reproduction ◽  
2011 ◽  
Vol 141 (3) ◽  
pp. 343-355 ◽  
Author(s):  
Michelle L Mujoomdar ◽  
Laura M Hogan ◽  
Albert F Parlow ◽  
Mark W Nachtigal
Keyword(s):  
Gene Expression ◽  
Ovarian Function ◽  
Elevated Serum ◽  
Cell Types ◽  
Reproductive Capacity ◽  
Wide Range ◽  
Altered Gene ◽  
Ovarian Pathology ◽  
Targeted Gene Expression ◽  
Benign Ovarian Tumors

Bioactivation of precursor proteins by members of the proprotein convertase (PC) family is essential for normal reproduction. ThePcsk6gene is a member of the PC family that is expressed in numerous ovarian cell types including granulosa cells and oocytes. We hypothesized that loss of PCSK6 would produce adverse effects in the mouse ovary. Mice incapable of expressing PCSK6 (Pcsk6tm1Rob) were obtained, and reproductive parameters (serum hormones, whelping interval, estrus cyclicity, and fertility) were compared toPcsk6+/+mice. WhilePcsk6tm1Robfemale mice are fertile, they manifest reduced reproductive capacity at an accelerated rate relative toPcsk6+/+mice. Reproductive senescence is typically reached by 9 months of age and is correlated with loss of estrus cyclicity, elevated serum FSH levels, and gross alterations in ovarian morphology. A wide range of ovarian morphologies were identified encompassing mild, such as an apparent reduction in follicle number, to moderate – ovarian atrophy with a complete absence of follicles – to severe, manifesting as normal ovarian structures replaced by benign ovarian tumors, including tubulostromal adenomas. Targeted gene expression profiling highlighted changes in RNA expression of molecules involved in processes such as steroidogenesis, gonadotropin signaling, transcriptional regulation, autocrine/paracrine signaling, cholesterol handling, and proprotein bioactivation. These results show that PCSK6 activity plays a role in maintaining normal cellular and tissue homeostasis in the ovary.

scholarly journals Follicular hormone dynamics during the midcycle surge of gonadotropins in women undergoing fertility treatment

2020 ◽  
Vol 26 (4) ◽  
pp. 256-268 ◽  
Author(s):  
L C Poulsen ◽  
A L M Englund ◽  
A S Andersen ◽  
J A Bøtkjær ◽  
L S Mamsen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reproductive Success ◽  
Follicular Fluid ◽  
Mixed Model ◽  
Transvaginal Ultrasound ◽  
Inhibin B ◽  
Fertility Treatment ◽  
Steroidogenic Enzymes ◽  
Inhibin A ◽  
Time Points

Abstract Changes in concentrations of intra-follicular hormones during ovulation are important for final oocyte maturation and endometrial priming to ensure reproductive success. As no human studies have investigated these changes in detail, our objective was to describe the dynamics of major follicular fluid (FF) hormones and transcription of steroidogenic enzymes and steroid receptors in human granulosa cells (GCs) during ovulation. We conducted a prospective cohort study at a public fertility clinic in 2016–2018. Fifty women undergoing ovarian stimulation for fertility treatment were included. From each woman, FF and GCs were collected by transvaginal ultrasound-guided follicle puncture of one follicle at two specific time points during ovulation, and the study covered a total of five time points: before ovulation induction (OI), 12, 17, 32 and 36 h after OI. Follicular fluid concentrations of oestradiol, progesterone, androstenedione, testosterone, 17-hydroxyprogesterone, anti-Mullerian hormone, inhibin A and inhibin B were measured using ELISA assays, and a statistical mixed model was used to analyse differences in hormone levels between time points. Gene expression of 33 steroidogenic enzymes and six hormone receptors in GCs across ovulation were assessed by microarray analysis, and selected genes were validated by quantitative reverse transcription PCR. We found that concentrations of oestradiol, testosterone, progesterone, AMH, inhibin A and inhibin B (P < 0.001) and gene expression of 12 steroidogenic enzymes and five receptors (false discovery rate < 0.0001) changed significantly during ovulation. Furthermore, we found parallel changes in plasma hormones. The substantial changes in follicular hormone production during ovulation highlight their importance for reproductive success.

Adrenergic induction of bimodal myocardial protection: signal transduction and cardiac gene reprogramming

1999 ◽  
Vol 276 (5) ◽  
pp. R1525-R1533 ◽  
Author(s):  
Xianzhong Meng ◽  
Brian D. Shames ◽  
Edward J. Pulido ◽  
Daniel R. Meldrum ◽  
Lihua Ao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Adaptive Response ◽  
Ischemia Reperfusion ◽  
Functional Adaptation ◽  
Immunofluorescent Staining ◽  
Northern Analysis ◽  
Cardiac Gene Expression ◽  
Cardiac Gene

This study tested the hypothesis that in vivo norepinephrine (NE) treatment induces bimodal cardiac functional protection against ischemia and examined the roles of α1-adrenoceptors, protein kinase C (PKC), and cardiac gene expression in cardiac protection. Rats were treated with NE (25 μg/kg iv). Cardiac functional resistance to ischemia-reperfusion (25/40 min) injury was examined 30 min and 1, 4, and 24 h after NE treatment with the Langendorff technique, and effects of α1-adrenoceptor antagonism and PKC inhibition on the protection were determined. Northern analysis was performed to examine cardiac expression of mRNAs encoding α-actin and myosin heavy chain (MHC) isoforms. Immunofluorescent staining was performed to localize PKC-βI in the ventricular myocardium. NE treatment improved postischemic functional recovery at 30 min, 4 h, and 24 h but not at 1 h. Pretreatment with prazosin or chelerythrine abolished both the early adaptive response at 30 min and the delayed adaptive response at 24 h. NE treatment induced intranuclear translocation of PKC-βI in cardiac myocytes at 10 min and increased skeletal α-actin and β-MHC mRNAs in the myocardium at 4–24 h. These results demonstrate that in vivo NE treatment induces bimodal myocardial functional adaptation to ischemia in a rat model. α1-Adrenoceptors and PKC appear to be involved in signal transduction for inducing both the early and delayed adaptive responses. The delayed adaptive response is associated with the expression of cardiac genes encoding fetal contractile proteins, and PKC-βI may transduce the signal for reprogramming of cardiac gene expression.

scholarly journals Phosphorylcholine Phosphatase: A Peculiar Enzyme of Pseudomonas aeruginosa

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Carlos Eduardo Domenech ◽  
Lisandro Horacio Otero ◽  
Paola Rita Beassoni ◽  
Angela Teresita Lisa
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Adaptive Response ◽  
Metal Ion ◽  
Coordination Geometry ◽  
Choline Metabolism ◽  
Inhibitory Site ◽  
Closed Structure ◽  
Phosphorylcholine Phosphatase ◽  
Hydrolysis Of

Pseudomonas aeruginosa synthesizes phosphorylcholine phosphatase (PchP) when grown on choline, betaine, dimethylglycine or carnitine. In the presence of Mg2+ or Zn2+, PchP catalyzes the hydrolysis of p-nitrophenylphosphate (p-NPP) or phosphorylcholine (Pcho). The regulation of pchP gene expression is under the control of GbdR and NtrC; dimethylglycine is likely the metabolite directly involved in the induction of PchP. Therefore, the regulation of choline metabolism and consequently PchP synthesis may reflect an adaptive response of P. aeruginosa to environmental conditions. Bioinformatic and biochemistry studies shown that PchP contains two sites for alkylammonium compounds (AACs): one in the catalytic site near the metal ion-phosphoester pocket, and another in an inhibitory site responsible for the binding of the alkylammonium moiety. Both sites could be close to each other and interact through the residues 42E, 43E and 82YYY84. Zn2+ is better activator than Mg2+ at pH 5.0 and it is more effective at alleviating the inhibition produced by the entry of Pcho or different AACs in the inhibitory site. We postulate that Zn2+ induces at pH 5.0 a conformational change in the active center that is communicated to the inhibitory site, producing a compact or closed structure. However, at pH 7.4, this effect is not observed because to the hydrolysis of the [Zn2+L2−1L20(H2O)2] complex, which causes a change from octahedral to tetrahedral in the metal coordination geometry. This enzyme is also present in P. fluorescens, P. putida, P. syringae, and other organisms. We have recently crystallized PchP and solved its structure.

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