The miR-98-3p/JAG1/Notch1 axis mediates the multigenerational inheritance of osteopenia caused by maternal dexamethasone exposure in female rat offspring
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Abstract:
As a synthetic glucocorticoid, dexamethasone is widely used to treat potential premature delivery and related diseases. Our previous studies have shown that prenatal dexamethasone exposure (PDE) can cause bone dysplasia and susceptibility to osteoporosis in female rat offspring. However, whether the effect of PDE on bone development can be extended to the third generation (F3 generation) and its multigenerational mechanism of inheritance have not been reported. In this study, we found that PDE delayed fetal bone development and reduced adult bone mass in female rat offspring of the F1 generation, and this effect of low bone mass caused by PDE even continued to the F2 and F3 generations. Furthermore, we found that PDE increases the expression of miR-98-3p but decreases JAG1/Notch1 signaling in the bone tissue of female fetal rats. Moreover, the expression changes of miR-98-3p/JAG1/Notch1 caused by PDE continued from the F1 to F3 adult offspring. Furthermore, the expression levels of miR-98-3p in oocytes of the F1 and F2 generations were increased. We also confirmed that dexamethasone upregulates the expression of miR-98-3p in vitro and shows targeted inhibition of JAG1/Notch1 signaling, leading to poor osteogenic differentiation of bone marrow mesenchymal stem cells. In conclusion, maternal dexamethasone exposure caused low bone mass in female rat offspring with a multigenerational inheritance effect, the mechanism of which is related to the inhibition of JAG1/Notch1 signaling caused by the continuous upregulation of miR-98-3p expression in bone tissues transmitted by F2 and F3 oocytes.Keywords:
JAG1
Osteopenia
Alagille Syndrome
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Osteopenia
Salmon calcitonin
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Abstract Food transfer is considered to provide infants with additional nutrients during weaning, and in fact, its frequency peaks around this time. However, the mechanisms underlying such food transfer remain unclear. In this study, we investigated whether adult common marmosets ( Callithrix jacchus ) change their tolerance to offspring begging for food depending on the offspring's age. We used four families consisting of breeding pairs, older offspring (29–49 weeks old), and younger offspring (7–15 weeks old). To directly compare the responses of a parent with its older and younger offspring, we placed one parent and one offspring in a testing space at one time. We presented foods where only the parent could reach them to ensure that the foods were transferred from the parent to offspring. Younger offspring showed more interest in food being held by the parents than older offspring. Parents refused older offspring more frequently than younger offspring and transferred food more often to younger offspring than to older offspring. There was no difference in all behavioral categories between fathers and mothers. These results suggest that both fathers and mothers are more tolerant to weanlings, but their tolerance decreases as offspring mature. Am. J. Primatol. 70:999–1002, 2008. © 2008 Wiley‐Liss, Inc.
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Females vary in the size of offspring that they produce, often in a manner that depends on maternal age or stage. This is puzzling, given that offspring size is predicted to evolve to a single optimal value where the gain in fitness from being larger exactly offsets the fitness lost to the mother by producing fewer offspring. We used a stage-structured life-history model to determine the optimal offspring size for females in different stages. We found that optimal offspring size does not vary with maternal stage when offspring fitness depends only on its size and not on the stage of the mother. This negative result holds even with density dependence, when larger offspring compete better. However, a trade-off between offspring size and maternal survival affects the optimal offspring size. The future reproductive value of the female, coupled with the costs and benefits of offspring investment, drives the evolution of stage-dependent offspring size. If producing larger offspring is riskier for mothers, females produce smaller offspring when their reproductive value in the next time step is large relative to current reproductive prospects. These analyses provide a novel framework for understanding why offspring size varies in age- and stage-structured populations.
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Maternal effects are increasingly recognized as important drivers of population dynamics and determinants of evolutionary trajectories. Recently, there has been a proliferation of studies finding or citing a positive relationship between maternal size/age and offspring size or offspring quality. The relationship between maternal phenotype and offspring size is intriguing in that it is unclear why young mothers should produce offspring of inferior quality or fitness. Here we evaluate the underlying evolutionary pressures that may lead to a maternal size/age-offspring size correlation and consider the likelihood that such a correlation results in a positive relationship between the age or size of mothers and the fitness of their offspring. We find that, while there are a number of reasons why selection may favor the production of larger offspring by larger mothers, this change in size is more likely due to associated changes in the maternal phenotype that affect the offspring size-performance relationship. We did not find evidence that the offspring of older females should have intrinsically higher fitness. When we explored this issue theoretically, the only instance in which smaller mothers produce suboptimal offspring sizes is when a (largely unsupported) constraint on maximum offspring size is introduced into the model. It is clear that larger offspring fare better than smaller offspring when reared in the same environment, but this misses a critical point: different environments elicit selection for different optimal sizes of young. We suggest that caution should be exercised when interpreting the outcome of offspring-size experiments when offspring from different mothers are reared in a common environment, because this approach may remove the source of selection (e.g., reproducing in different context) that induced a shift in offspring size in the first place. It has been suggested that fish stocks should be managed to preserve these older age classes because larger mothers produce offspring with a greater chance of survival and subsequent recruitment. Overall, we suggest that, while there are clear and compelling reasons for preserving older females in exploited populations, there is little theoretical justification or evidence that older mothers produce offspring with higher per capita fitness than do younger mothers.
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Studies have investigated the associations between parental metabolic syndrome (MetS) and offspring MetS. This study aimed to uncover parental-offspring associations for MetS and its components according to offspring sex and age.A cross-sectional study in 1,403 fathers, 1,451 mothers, and 1,532 offspring (340 male and 404 female offspring aged 10-18 years; 283 male and 505 female offspring aged 19-25 years) using the Korea National Health and Nutrition Examination Survey data between 2010 and 2013.All categorized MetS components in fathers and mothers were significantly associated with the same components in male offspring, while high waist circumference, high triglycerides, and low high-density lipoprotein in fathers and mothers were associated with the same components in female offspring. The number of categorized MetS components which were significantly associated between parent-offspring pairs was greater in offspring aged 19-25 years than in those aged 10-18 years. All categorized MetS components were significantly associated between father-male offspring aged 19-25 years pairs, but not in other parent-offspring pairs. The MetS per se in fathers and mothers was significantly associated with that in male offspring aged 10-18 years.There were differential associations according to offspring sex and age group and parent's sex with respect to parental-offspring associations for MetS and its individual components. The associations for MetS and its components were stronger in young adult versus adolescent offspring, in male offspring versus female offspring.
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Maternal effects are increasingly recognized as important drivers of population dynamics and determinants of evolutionary trajectories. Recently, there has been a proliferation of studies finding or citing a positive relationship between maternal size/age and offspring size or offspring quality. The relationship between maternal phenotype and offspring size is intriguing in that it is unclear why young mothers should produce offspring of inferior quality or fitness. Here we evaluate the underlying evolutionary pressures that may lead to a maternal size/age–offspring size correlation and consider the likelihood that such a correlation results in a positive relationship between the age or size of mothers and the fitness of their offspring. We find that, while there are a number of reasons why selection may favor the production of larger offspring by larger mothers, this change in size is more likely due to associated changes in the maternal phenotype that affect the offspring size–performance relationship. We did not find evidence that the offspring of older females should have intrinsically higher fitness. When we explored this issue theoretically, the only instance in which smaller mothers produce suboptimal offspring sizes is when a (largely unsupported) constraint on maximum offspring size is introduced into the model. It is clear that larger offspring fare better than smaller offspring when reared in the same environment, but this misses a critical point: different environments elicit selection for different optimal sizes of young. We suggest that caution should be exercised when interpreting the outcome of offspring-size experiments when offspring from different mothers are reared in a common environment, because this approach may remove the source of selection (e.g., reproducing in different context) that induced a shift in offspring size in the first place. It has been suggested that fish stocks should be managed to preserve these older age classes because larger mothers produce offspring with a greater chance of survival and subsequent recruitment. Overall, we suggest that, while there are clear and compelling reasons for preserving older females in exploited populations, there is little theoretical justification or evidence that older mothers produce offspring with higher per capita fitness than do younger mothers.
Maternal effect
Parent–offspring conflict
Affect
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