Annual Medical Student Research Forum
Permanent URI for this collectionhttps://hdl.handle.net/2152.5/1482
This collection contains posters and related content from the Annual Medical Student Research Forums. The Annual Medical Student Research Forum began in 1962. Citations for items published from 2021 to the present are formatted according to the Publication Manual of the American Psychological Association, 7th edition, ©2020. (Older citations are formatted according to the Publication Manual of the American Psychological Association, 6th edition, ©2010.)
Booklets prior to 2013 are available in the archives. Contact archives@utsouthwestern.edu to make an appointment to access the earlier printed booklets.
News
The 62nd Annual Medical Student Research Forum was held January 30, 2024. Selected posters are now available in this collection.
Browse
Browsing Annual Medical Student Research Forum by Subject "25-Hydroxyvitamin D3 1-alpha-Hydroxylase"
Now showing 1 - 2 of 2
- Results Per Page
- Sort Options
Item Calcitriol Treatment Suppresses Contraction-Associated Gene Expression in Pregnant Mice Near Term(2018-01-23) Morgan, Kelsi; Yang, Ailling; Montalbano, Alina P.; Mendelson, Carole R.Preterm birth (PTB) is the leading cause of infant mortality during the first four weeks of life world-wide. This is due, in part, to our incomplete understanding of the mechanisms that mediate uterine quiescence during most of pregnancy and promote the transition to labor at term. Term and preterm labor are associated with increased levels of proinflammatory cytokines within maternal reproductive tissues where they activate inflammatory transcription factors (e.g. NF-κB) that enhance expression of genes encoding contraction-associated proteins (CAP) (i.e. connexin-43 (CX-43)), oxytocin receptor (OXTR)). By contrast, uterine quiescence is maintained throughout most of pregnancy by increased progesterone (P4) levels and enhanced progesterone receptor (PR) activity, which silence expression of proinflammatory mediators and CAP genes. Treatment of pregnant women at risk for preterm labor with progestins has negligible effects - underscoring the need for novel therapeutic targets. To identify such targets, our lab surveyed the myometrial transcriptome of timed-pregnant mice at 15.5-18.5 days post-coitum (dpc) and during labor at term (19.0 dpc) using RNA-sequencing. Interestingly, Cyp27b1 was one of the most highly downregulated transcripts at 18.5 dpc and in-labor, compared to 15.5 dpc. Cyp27b1 encodes 1α-hydroxylase, the key enzyme responsible for synthesis of the active form of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol) which binds to the vitamin D receptor (VDR). Calcitriol/VDR have anti-inflammatory actions and are reported to mediate maternal tolerance to the hemi-allogeneic fetus. Interestingly, we previously observed that P4 treatment of timed-pregnant mice caused a significant increase in myometrial CYP27B1 mRNA levels, compared to controls. In the present study, we sought to assess effects of calcitriol treatment on CAP gene expression in timed-pregnant mice. To this end, pregnant mice were injected s.c. daily from 13.5-17.5 dpc with vehicle (n=3) of with 3 μg/kg of calcitriol (n=4). Mice were sacrificed and myometrial tissues were collected at 18.5 dpc. RT-qPCR revealed significantly reduced levels of CX43 (p<0.0001) and OXTR (p<0.05) in myometrium of calcitriol treated mice, compared to controls. Collectively, these data suggest that the decrease in Cyp27b1 expression, coupled with the decline in PR function near term may contribute to increased CAP gene expression leading to myometrial contractility and labor. Cyp27b1 may serve as a key P4/PR target gene that acts cooperatively to maintain myometrial quiescence via its anti-inflammatory actions. Thus, calcitriol may be a safe and effective treatment for the prevention of PTB.Item The Role of Vitamin D Metabolism in the Timing of Birth(2018-01-23) Yang, Ailing; Montalbano, Alina; Mendelson, CarolePreterm birth (PTB, <37 weeks of gestation) is the leading cause of neonatal mortality and morbidity. Both term and preterm labor are associated with increased levels of proinflammatory cytokines within fetal and maternal reproductive tissues. Uterine quiescence is maintained throughout most of pregnancy by increased circulating progesterone (P4) and enhanced progesterone receptor (PR) activity, which silence expression of proinflamᆲmatory mediators and contraction-associated genes. To identify novel genes that maintain uterine quiescence during pregnancy and promote the initiation of term and preterm labor, our lab conducted RNA sequencing of myometrium from timed-pregnant mice at 15.5-18.5 days post-coitum (dpc) and during labor (19.0 dpc). Novel genes of interest were identified through transcriptome profiling and validated by quantitative real-time PCR. Cyp27b1 was one of the most highly downregulated transcripts in pregnant mouse myometrium at 18.5 dpc and in-labor, compared to 15.5 dpc. Cyp27b1 1α-hydroxylase, the key enzyme in synthesis of the bioactive form of vitamin D, calcitriol, which binds to the vitamin D receptor (VDR), a member of the steroid/nuclear receptor family, which was also downregulated at term. Calcitriol/VDR mediate anti-inflammatory actions in various tissues; calcitriol synthesized by human placenta, decidual macrophages and uterine natural killer cells was reported to regulate maternal immunologic tolerance to the hemi-allogeneic fetus during pregnancy. The effect of P4 and of the PR antagonist, RU486, on Cyp27b1/VDR mRNA expression was analyzed. We observed that P4 treatment of timed-pregnant mice caused a significant increase in myometrial CYP27B1 mRNA levels compared to time-matched controls in labor at term. In RU486-treated mice, CYP27B1 mRNA decreased signifi-cantly 8 hours post-injection and remained significantly reduced during preterm labor, compared to vehicle-injected mice. Based on these collective findings, we postulate that CYP27B1 and VDR are key P4/PR target genes in the pregnant myometrium that act cooperatively with P4/PR to maintain myometrial quiescence via their anti-inflammatory actions. Thus, the decline in PR function near term, accompanied by a parallel decline in CYP27B1/VDR, permit increased inflammatory gene expression leading to myometrial contractility and labor. We hypothesize that calcitriol may provide a safe and effective treatment for prevention of PTB.