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Moley, K.

Publications and source records attributed to Moley, K..

2 recordsLinked to original sources

Maternal high-fat/high-sugar diet has short-term dental effects and long-term sex-specific skeletal effects on adult offspring mice

BackgroundMaternal nutrition is increasingly recognized as a modulator of offspring skeletal development. While genetics has long been considered the primary determinant of craniofacial morphology, emerging evidence suggests that prenatal and early postnatal dietary exposures also influence facial morphology. However, how maternal diet differentially affects male and female craniofacial structures remains unclear. This study aimed to examine the effects of a maternal high-fat, high-sugar (HFHS) diet on craniofacial and dental morphology in first-(F1) and second-(F2) generation adult mice. Materials and MethodsFemale mice were fed a HFHS diet for six weeks before mating and throughout pregnancy and lactation. F1 offspring were weaned to a standard chow diet, and a subset of female F1 offspring were bred to produce F2 offspring, also maintained on chow. Craniofacial skeletal and dental structures of adult F1 and F2 mice at 1-year of age were assessed using micro-computed tomography for linear and geometric morphometrics. ResultsHFHS diet exposure significantly reduced midfacial and mandibular length in F1 females, and these effects persisted in F2 females. Mandibular shape differences were also observed in both generations of females. In males, skull size remained unchanged, though subtle mandibular shape changes were noted in F1 only. Tooth size was reduced in both sexes of F1 offspring but not in F2. ConclusionMaternal HFHS diet induces sex- and jaw-specific alterations in craniofacial morphology, with skeletal changes persisting in females across generations, while dental effects did not persist beyond one generation. These findings highlight the potential for maternal dietary habits to exert lasting, intergenerational influences on offspring facial form.

developmental biology↗

The autophagy protein, ATG14 safeguards against unscheduled pyroptosis activation to enable embryo transport during early pregnancy

Recurrent pregnancy loss (RPL), characterized by two or more failed clinical pregnancies, poses a significant challenge to reproductive health. In addition to embryo quality and endometrial function, proper oviduct function is also essential for successful pregnancy establishment. Therefore, structural abnormalities or inflammation resulting from infection in the oviduct may impede the transport of embryos to the endometrium, thereby increasing the risk of miscarriage. However, our understanding of the biological processes that preserve the oviductal cellular structure and functional integrity is limited. Here, we report that autophagy-related protein ATG14 plays a crucial role in maintaining the cellular integrity of the oviduct by controlling inflammatory responses, thereby supporting efficient embryo transport. Specifically, the conditional depletion of the autophagy-related gene, Atg14 in the oviduct causes severe structural abnormalities compromising its cellular integrity leading to the abnormal retention of embryos. Interestingly, the selective loss of Atg14 in oviduct ciliary epithelial cells did not impact female fertility, highlighting the specificity of ATG14 function in distinct cell types within the oviduct. Mechanistically, loss of Atg14 triggered unscheduled pyroptosis via altering the mitochondrial integrity leading to inappropriate embryo retention and impeded embryo transport in the oviduct. Finally, pharmacological activation of pyroptosis in pregnant mice phenocopied the genetically induced defect and caused impairment in embryo transport. Together, we found that ATG14 safeguards against unscheduled pyroptosis activation to enable embryo transport from the oviduct to uterus for the successful implantation. Of clinical significance, these findings provide possible insights into the underlying mechanism(s) of early pregnancy loss and might aid in developing novel prevention strategies using autophagy modulators.

developmental biology↗