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  1. Article ; Online: Vitamin D and miscarriage: a systematic review and meta-analysis.

    Tamblyn, Jennifer A / Pilarski, Nicole S P / Markland, Alexandra D / Marson, Ella J / Devall, Adam / Hewison, Martin / Morris, Rachel K / Coomarasamy, Arri

    Fertility and sterility

    2022  Volume 118, Issue 1, Page(s) 111–122

    Abstract: Objective: To investigate whether a significant association between vitamin D status and the risk of miscarriage or recurrent miscarriage (RM) exists.: Design: Systematic review and meta-analysis.: Setting: Not applicable.: Patient(s): Women ... ...

    Abstract Objective: To investigate whether a significant association between vitamin D status and the risk of miscarriage or recurrent miscarriage (RM) exists.
    Design: Systematic review and meta-analysis.
    Setting: Not applicable.
    Patient(s): Women with miscarriage and RM.
    Intervention(s): We searched the Ovid MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials from database inception to May 2021. Randomized and observational studies investigating the association between maternal vitamin D status and miscarriage and/or vitamin D treatment and miscarriage were included.
    Main outcome measure(s): The primary outcome was miscarriage or RM, with vitamin D status used as the predictor of risk. Whether vitamin D treatment reduces the risk of miscarriage and RM was also assessed.
    Result(s): Of 902 studies identified, 10 (n = 7,663 women) were included: 4 randomized controlled trials (n = 666 women) and 6 observational studies (n = 6,997 women). Women diagnosed with vitamin D deficiency (<50 nmol/L) had an increased risk of miscarriage compared with women who were vitamin D replete (>75 nmol/L) (odds ratio, 1.94; 95% confidence interval, 1.25-3.02; 4 studies; n = 3,674; I
    Conclusion(s): Vitamin D deficiency and insufficiency are associated with miscarriage. Whether preconception treatment of vitamin D deficiency protects against pregnancy loss in women at risk of miscarriage remains unknown.
    Registration number: CRD42021259899.
    MeSH term(s) Abortion, Habitual/diagnosis ; Abortion, Habitual/epidemiology ; Abortion, Habitual/prevention & control ; Female ; Humans ; Pregnancy ; Vitamin D/therapeutic use ; Vitamin D Deficiency/complications ; Vitamin D Deficiency/diagnosis ; Vitamin D Deficiency/drug therapy ; Vitamins/therapeutic use
    Chemical Substances Vitamins ; Vitamin D (1406-16-2)
    Language English
    Publishing date 2022-05-28
    Publishing country United States
    Document type Journal Article ; Meta-Analysis ; Review ; Systematic Review
    ZDB-ID 80133-1
    ISSN 1556-5653 ; 0015-0282
    ISSN (online) 1556-5653
    ISSN 0015-0282
    DOI 10.1016/j.fertnstert.2022.04.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Trophoblast uptake of DBP regulates intracellular actin and promotes matrix invasion.

    Ganguly, Ankana / Tamblyn, Jennifer A / Shattock, Alexandra / Joseph, Annsha / Larner, Dean P / Jenkinson, Carl / Gupta, Janesh / Gross, Stephane R / Hewison, Martin

    The Journal of endocrinology

    2021  Volume 249, Issue 1, Page(s) 43–55

    Abstract: Early pregnancy is characterised by elevated circulating levels of vitamin D binding protein (DBP). The impact of this on maternal and fetal health is unclear but DBP is present in the placenta, and DBP gene variants have been linked to malplacentation ... ...

    Abstract Early pregnancy is characterised by elevated circulating levels of vitamin D binding protein (DBP). The impact of this on maternal and fetal health is unclear but DBP is present in the placenta, and DBP gene variants have been linked to malplacentation disorders such as preeclampsia. The functional role of DBP in the placenta was investigated using trophoblastic JEG3, BeWo and HTR8 cells. All three cell lines showed intracellular DBP with increased expression and nuclear localisation of DBP in cells treated with the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D). When cultured in the serum of mice lacking DBP (DBP-/-), JEG3 cells showed no intracellular DBP indicating uptake of exogenous DBP. Inhibition of the membrane receptor for DBP, megalin, also suppressed intracellular DBP. Elimination of intracellular DBP with DBP-/- serum or megalin inhibitor suppressed matrix invasion by trophoblast cells and was associated with increased nuclear accumulation of G-actin. Conversely, treatment with 1,25D enhanced matrix invasion. This was independent of the nuclear vitamin D receptor but was associated with enhanced ERK phosphorylation, and inhibition of ERK kinase suppressed trophoblast matrix invasion. When cultured with serum from pregnant women, trophoblast matrix invasion correlated with DBP concentration, and DBP was lower in first-trimester serum from women who later developed preeclampsia. These data show that the trophoblast matrix invasion involves uptake of serum DBP and associated intracellular actin-binding and homeostasis. DBP is a potential marker of placentation disorders such as preeclampsia and may also provide a therapeutic option for improved placenta and pregnancy health.
    MeSH term(s) Actins/metabolism ; Cell Line ; Cell Line, Tumor ; Cell Nucleus/chemistry ; Cell Nucleus/metabolism ; Choriocarcinoma ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; Gene Knockdown Techniques ; Humans ; Phosphorylation ; Placentation/physiology ; Pre-Eclampsia/blood ; Pregnancy ; Receptors, Calcitriol/genetics ; Receptors, Calcitriol/physiology ; Trophoblasts/physiology ; Uterine Neoplasms ; Vitamin D/analogs & derivatives ; Vitamin D/blood ; Vitamin D/pharmacology ; Vitamin D-Binding Protein/blood ; Vitamin D-Binding Protein/genetics ; Vitamin D-Binding Protein/physiology
    Chemical Substances Actins ; Receptors, Calcitriol ; Vitamin D-Binding Protein ; Vitamin D (1406-16-2) ; 1,25-dihydroxyvitamin D (66772-14-3) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24)
    Language English
    Publishing date 2021-02-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 3028-4
    ISSN 1479-6805 ; 0022-0795
    ISSN (online) 1479-6805
    ISSN 0022-0795
    DOI 10.1530/JOE-20-0626
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: 11-Oxygenated Estrogens Are a Novel Class of Human Estrogens but Do not Contribute to the Circulating Estrogen Pool.

    Barnard, Lise / Schiffer, Lina / Louw du-Toit, Renate / Tamblyn, Jennifer A / Chen, Shiuan / Africander, Donita / Arlt, Wiebke / Foster, Paul A / Storbeck, Karl-Heinz

    Endocrinology

    2021  Volume 162, Issue 3

    Abstract: Androgens are the obligatory precursors of estrogens. In humans, classic androgen biosynthesis yields testosterone, thought to represent the predominant circulating active androgen both in men and women. However, recent work has shown that 11- ... ...

    Abstract Androgens are the obligatory precursors of estrogens. In humans, classic androgen biosynthesis yields testosterone, thought to represent the predominant circulating active androgen both in men and women. However, recent work has shown that 11-ketotestosterone, derived from the newly described 11-oxygenated androgen biosynthesis pathway, makes a substantial contribution to the active androgen pool in women. Considering that classic androgens are the obligatory substrates for estrogen biosynthesis catalyzed by cytochrome P450 aromatase, we hypothesized that 11-oxygenated androgens are aromatizable. Here we use steroid analysis by tandem mass spectrometry to demonstrate that human aromatase generates 11-oxygenated estrogens from 11-oxygenated androgens in 3 different cell-based aromatase expression systems and in human ex vivo placenta explant cultures. We also show that 11-oxygenated estrogens are generated as a byproduct of the aromatization of classic androgens. We show that 11β-hydroxy-17β-estradiol binds and activates estrogen receptors α and β and that 11β-hydroxy-17β-estradiol and the classic androgen pathway-derived active estrogen, 17β-estradiol, are equipotent in stimulating breast cancer cell line proliferation and expression of estrogen-responsive genes. 11-oxygenated estrogens were, however, not detectable in serum from individuals with high aromatase levels (pregnant women) and elevated 11-oxygenated androgen levels (patients with congenital adrenal hyperplasia or adrenocortical carcinoma). Our data show that while 11-oxygenated androgens are aromatizable in vitro and ex vivo, the resulting 11-oxygenated estrogens are not detectable in circulation, suggesting that 11-oxygenated androgens function primarily as androgens in vivo.
    MeSH term(s) Animals ; Aromatase/metabolism ; COS Cells ; Cell Line, Tumor ; Chlorocebus aethiops ; Estradiol/analogs & derivatives ; Estradiol/chemistry ; Estradiol/metabolism ; Estrogens/analogs & derivatives ; Estrogens/blood ; Estrogens/chemistry ; Female ; Fetal Blood/chemistry ; Fetal Blood/metabolism ; HEK293 Cells ; Humans ; Infant, Newborn ; MCF-7 Cells ; Oxygen/chemistry ; Placenta/chemistry ; Placenta/metabolism ; Pregnancy/blood ; Protein Binding/drug effects ; Receptors, Estrogen/metabolism ; Testosterone/analogs & derivatives ; Testosterone/blood ; Testosterone/chemistry
    Chemical Substances Estrogens ; Receptors, Estrogen ; Testosterone (3XMK78S47O) ; Estradiol (4TI98Z838E) ; Aromatase (EC 1.14.14.1) ; CYP19A1 protein, human (EC 1.14.14.1) ; 11-ketotestosterone (KF38W1A85U) ; Oxygen (S88TT14065)
    Language English
    Publishing date 2021-01-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/endocr/bqaa231
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Vitamin D Promotes Trophoblast Cell Induced Separation of Vascular Smooth Muscle Cells in Vascular Remodeling

    Zhang, Joy Yue / Wu, Peihuang / Chen, Danyang / Ning, Fen / Lu, Qinsheng / Qiu, Xiu / Hewison, Martin / Tamblyn, Jennifer A / Kilby, Mark D / Lash, Gendie E

    Frontiers in cell and developmental biology

    2020  Volume 8, Page(s) 601043

    Abstract: Vitamin D deficiency is associated with complications of pregnancy such as pre-eclampsia, fetal growth restriction, and miscarriage, all of which are also associated with incomplete spiral artery (SpA) remodeling. We have previously shown that both ... ...

    Abstract Vitamin D deficiency is associated with complications of pregnancy such as pre-eclampsia, fetal growth restriction, and miscarriage, all of which are also associated with incomplete spiral artery (SpA) remodeling. We have previously shown that both uterine natural killer (uNK) cells and extravillous trophoblast cells (EVT) are required for successful SpA remodeling, but whether their activity in this process is modulated by vitamin D is not known. In the current study, we use a previously described chorionic plate artery (CPA)
    Language English
    Publishing date 2020-12-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2020.601043
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Management of obstetric postpartum hemorrhage: a national service evaluation of current practice in the UK.

    Al Wattar, Bassel H / Tamblyn, Jennifer A / Parry-Smith, William / Prior, Mathew / Van Der Nelson, Helen

    Risk management and healthcare policy

    2017  Volume 10, Page(s) 1–6

    Abstract: Background: Postpartum hemorrhage (PPH) continues to be one of the major causes of maternal mortality and morbidity in obstetrics. Variations in practice often lead to adverse maternity outcomes following PPH. Our objective was to assess the current ... ...

    Abstract Background: Postpartum hemorrhage (PPH) continues to be one of the major causes of maternal mortality and morbidity in obstetrics. Variations in practice often lead to adverse maternity outcomes following PPH. Our objective was to assess the current practice in managing PPH in the UK.
    Methods: We performed a national multicenter prospective service evaluation study over one calendar month and compared the current performance to national standards for managing PPH. We used a standardized data collection tool and collected data on patients' demographics, incidence of PPH, estimated blood loss (EBL), prophylactic and treatment measures, onset of labor, and mode of delivery.
    Results: We collected data from 98 obstetric units, including 3663 cases of primary PPH. Fifty percent of cases were minor PPH (EBL 500-1000 mL, n=1900/3613, 52.6%) and the remaining were moderate PPH (EBL >1000 to <2000 mL, n=1424/3613, 39.4%) and severe PPH (EBL >2000 mL, n=289/3613, 8%). The majority of women received active management of the third stage of labor (3504/3613, 97%) most commonly with Syntometrine intramuscular (1479/3613, 40.9%). More than half required one additional uterotonic agent (2364/3613, 65.4%) most commonly with Syntocinon intravenous infusion (1155/2364, 48.8%). There was a poor involvement of consultant obstetricians and anesthetists in managing PPH cases, which was more prevalent when managing major PPH (
    Conclusion: There are still variations in managing PPH in the UK against national guidelines. More senior doctor involvement and regular service evaluation are needed to improve maternal outcomes following PPH.
    Language English
    Publishing date 2017-01-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2495128-6
    ISSN 1179-1594
    ISSN 1179-1594
    DOI 10.2147/RMHP.S121737
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Vitamin D-deficiency and sex-specific dysregulation of placental inflammation.

    Liu, Nancy Q / Larner, Dean P / Yao, Qingqiang / Chun, Rene F / Ouyang, Yuxin / Zhou, Rui / Tamblyn, Jennifer A / Wagner, Carol L / Hewison, Martin

    The Journal of steroid biochemistry and molecular biology

    2017  Volume 177, Page(s) 223–230

    Abstract: To investigate an immunomodulatory role for vitamin D in pregnancy we used mice raised on vitamin D-sufficient (SUFF), or -deficient (DEF) diets. At embryonic day 14, pregnant mice received intraperitoneal injection of lipopolysaccharide (LPS) or vehicle ...

    Abstract To investigate an immunomodulatory role for vitamin D in pregnancy we used mice raised on vitamin D-sufficient (SUFF), or -deficient (DEF) diets. At embryonic day 14, pregnant mice received intraperitoneal injection of lipopolysaccharide (LPS) or vehicle for 24h, with age-matched non-pregnant mice as controls. In non-pregnant mice, 6 serum analytes (IL-1β, IL-18, MDC/CCL22, MIP-1α/CCL3, EGF, IgA) were lower in DEF mice. In pregnant DEF mice only GH was higher. In non-pregnant mice LPS induced 28 analytes, with 5 (IL-18, IP-10/CXCL10, MCP-1/CCL2, MIP-1β/CCL4, MIP-3β/CCL19) being highest in DEF mice. In pregnant SUFF mice 16 serum analytes increased with LPS, and 6 of these (IP-10/CXCL10, MCP-1/CCL2, SAP, TIMP-1, VCAM-1, vWF) were higher and 1 (GCP-2/CXCL6) lower in DEF mice. Parallel analysis of placental mRNAs showed elevated mRNA for Il-6, Ccl2 and Cxcl10 in placentae from male and female fetuses in LPS-DEF mice. However, LPS-induced expression of Ifnγ, Tnfα, and Cxcl6 was only observed in female placentae from DEF mice. LPS-DEF mice also showed smaller litter sizes relative to control SUFF mice. Numbers of female fetuses per dam were significantly lower for DEF mice with or without LPS challenge. LPS had no effect on numbers of male fetuses from DEF mothers, but significantly decreased male fetuses from SUFF mothers. These data indicate that vitamin D is an important component of anti-inflammatory immune responses during pregnancy, with the placenta and fetal sex playing pivotal roles in this process.
    MeSH term(s) 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics ; Animals ; Cytokines/genetics ; Female ; Fetus/metabolism ; Inflammation/metabolism ; Lipopolysaccharides/pharmacology ; Litter Size ; Male ; Mice, Inbred C57BL ; Placenta/metabolism ; Pregnancy ; RNA, Messenger/metabolism ; Receptors, Calcitriol/genetics ; Sex Characteristics ; Vitamin D Deficiency/metabolism ; Vitamin D3 24-Hydroxylase/genetics
    Chemical Substances Cytokines ; Lipopolysaccharides ; RNA, Messenger ; Receptors, Calcitriol ; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase (EC 1.14.13.13) ; Cyp24a1 protein, mouse (EC 1.14.15.16) ; Vitamin D3 24-Hydroxylase (EC 1.14.15.16)
    Language English
    Publishing date 2017-07-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1049188-0
    ISSN 1879-1220 ; 0960-0760
    ISSN (online) 1879-1220
    ISSN 0960-0760
    DOI 10.1016/j.jsbmb.2017.06.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Vitamin D, the placenta and early pregnancy: effects on trophoblast function.

    Ganguly, Ankana / Tamblyn, Jennifer A / Finn-Sell, Sarah / Chan, Shiao-Y / Westwood, Melissa / Gupta, Janesh / Kilby, Mark D / Gross, Stephane R / Hewison, Martin

    The Journal of endocrinology

    2017  Volume 236, Issue 2, Page(s) R93–R103

    Abstract: Pregnancy is associated with significant changes in vitamin D metabolism, notably increased maternal serum levels of active vitamin D, 1,25-dihydroxyvitamin (1,25(OH) ...

    Abstract Pregnancy is associated with significant changes in vitamin D metabolism, notably increased maternal serum levels of active vitamin D, 1,25-dihydroxyvitamin (1,25(OH)
    MeSH term(s) Animals ; Embryo Implantation/physiology ; Female ; Gestational Age ; Humans ; Placenta/physiology ; Pregnancy ; Pregnancy Outcome ; Trophoblasts/physiology ; Vitamin D/physiology ; Vitamin D Deficiency/complications ; Vitamin D Deficiency/physiopathology
    Chemical Substances Vitamin D (1406-16-2)
    Language English
    Publishing date 2017-11-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 3028-4
    ISSN 1479-6805 ; 0022-0795
    ISSN (online) 1479-6805
    ISSN 0022-0795
    DOI 10.1530/JOE-17-0491
    Database MEDical Literature Analysis and Retrieval System OnLINE

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