Browsing by Subject "Gestation"

Now showing 1 - 3 of 3
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    Activation of Proneuronal Transcription Factor Ascl1 in Maternal Liver Ensures a Healthy Pregnancy
    (Elsevier, 2022) Lee, Joonyong; Garcia, Veronica; Nambiar, Shashank M.; Jiang, Huaizhou; Dai, Guoli; Biology, School of Science
    Background & aims: Maternal liver shows robust adaptations to pregnancy to accommodate the metabolic needs of the developing and growing placenta and fetus by largely unknown mechanisms. We found that Ascl1, a gene encoding a basic helix-loop-helix transcription factor essential for neuronal development, is highly activated in maternal hepatocytes during the second half of gestation in mice. Methods: To investigate whether and how Ascl1 plays a pregnancy-dependent role, we deleted the Ascl1 gene specifically in maternal hepatocytes from midgestation until term. Results: As a result, we identified multiple Ascl1-dependent phenotypes. Maternal livers lacking Ascl1 showed aberrant hepatocyte structure, increased hepatocyte proliferation, enlarged hepatocyte size, reduced albumin production, and increased release of liver enzymes, indicating maternal liver dysfunction. Simultaneously, maternal pancreas and spleen and the placenta showed marked overgrowth; and the maternal ceca microbiome showed alterations in relative abundance of several bacterial subpopulations. Moreover, litters born from maternal hepatic Ascl1-deficient dams experienced abnormal postnatal growth after weaning, implying an adverse pregnancy outcome. Mechanistically, we found that maternal hepatocytes deficient for Ascl1 showed robust activation of insulin-like growth factor 2 expression, which may contribute to the Ascl1-dependent phenotypes widespread in maternal and uteroplacental compartments. Conclusions: In summary, we show that maternal liver, via activating Ascl1 expression, modulates the adaptations of maternal organs and the growth of the placenta to maintain a healthy pregnancy. Our studies show that Ascl1 is a novel and critical regulator of the physiology of pregnancy.
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    Embryo Adoption: Implications of Personhood, Marriage, and Parenthood
    (2008-04-14T12:30:19Z) McMillen, Brooke Marie; Brand, Peggy Zeglin; Eberl, Jason T.; Burke, Michael B.
    One’s personal claims regarding personhood will influence his moral belief regarding embryo adoption. In Chapter One, I consider the personhood of the human embryo. If the human embryo is a person, we are morally obligated to permit the practice of embryo adoption as an ethical means to save human persons. However, for those who do not claim that an embryo is a person at conception, embryo adoption is not a necessary practice because we have no moral obligation to protect them. There are still others who claim that personhood is gained at some point during gestation when certain mental capacities develop. I offer my own claim that consciousness and sentience as well as the potential to be self-conscious mark the beginning of personhood. Embryo adoption raises several questions surrounding the institution of marriage. Due to its untraditional method of procreation, embryo adoption calls into question the role of procreation within marriage. In Chapter Two, I explore the nature of the marriage relationship by offering Lisa Cahill’s definition of marriage which involves both a spiritual and physical dimension, and then I describe the concept of marriage from different perspectives including a social, religious, and a personal perspective. From a personal perspective, I explore the relationship between marriage and friendship. Finally, I describe how the concept of marriage is understood today and explore the advantages to being married as opposed to the advantages of being single. Embryo adoption changes the way we customarily think about procreation within a family because in embryo adoption, couples are seeking an embryo from another union to be implanted into the woman. This prompts some philosophers to argue that embryo adoption violates the marriage relationship. In Chapter Three, I further consider the impact of embryo adoption on the family as an extension of the marital relationship as well as the impact of embryo adoption on the traditional roles of motherhood and fatherhood. I examine motherhood by looking at how some philosophers define motherhood and when these philosophers claim a woman becomes a mother. After considering these issues regarding motherhood, I examine the same issues surrounding fatherhood. Peg Brand, PhD., Chair
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    Prenatal Opioid Exposure Enhances Responsiveness to Future Drug Reward and Alters Sensitivity to Pain: A Review of PreclinicalModels and Contributing Mechanisms
    (The Society for Neuroscience, 2020-10-15) Grecco, Gregory G.; Atwood, Brady K.; Pharmacology and Toxicology, School of Medicine
    The opioid crisis has resulted in an unprecedented number of neonates born with prenatal opioid exposure (POE); however, the long-term effects of POE on offspring behavior and neurodevelopment remain relatively unknown. The advantages and disadvantages of the various preclinical POE models developed over the last several decades are discussed in the context of clinical and translational relevance. Although considerable and important variability exists among preclinical models of POE, the examination of these preclinical models has revealed that opioid exposure during the prenatal period contributes to maladaptive behavioral development as offspring mature including an altered responsiveness to rewarding drugs and increased pain response. The present review summarizes key findings demonstrating the impact of POE on offspring drug self-administration (SA), drug consumption, the reinforcing properties of drugs, drug tolerance, and other reward-related behaviors such as hypersensitivity to pain. Potential underlying molecular mechanisms which may contribute to this enhanced addictive phenotype in POE offspring are further discussed with special attention given to key brain regions associated with reward including the striatum, prefrontal cortex (PFC), ventral tegmental area (VTA), hippocampus, and amygdala. Improvements in preclinical models and further areas of study are also identified which may advance the translational value of findings and help address the growing problem of POE in clinical populations.