Vitamin C and vitamin E in pregnant women at risk of pre-eclampsia.
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Asthma↗
Biomedical subjects
Stuart Campbell
Publications and source records attributed to Stuart Campbell.
Is vitamin E a safe prophylaxis for preeclampsia?
The prophylactic use of vitamins E and C for the prevention of preeclampsia is currently being evaluated in multiple clinical trials in Canada, Mexico, the United Kingdom, the United States, and other developing countries. In addition to its antioxidant capacity, exogenous vitamin E may prevent an immunologic switch (Th1 to Th2) that is vital for early-to late transition in normal pregnancies. Moreover, vitamin E could be a potential interferon-gamma (IFN-gamma) mimic facilitating persistent proinflammatory reactions at the fetal-maternal interface. These untoward effects of dietary intake of vitamin E may be more pronounced in those treated cases that fail to develop preeclampsia. A critical test of this hypothesis would be to establish whether, under variable O2 tension, vitamin E is capable of affecting cytokine signaling in placental trophoblasts and maternal immune effector cells, both in early and late human pregnancies.
Antioxidants↗
First trimester screening for preeclampsia.
PURPOSE OF REVIEW: Aspirin therapy from the first trimester of pregnancy may benefit women at high risk for preeclampsia. We review publications from the past year that examine first-trimester screening studies for preeclampsia. RECENT FINDINGS: For a false positive rate of 5%, first-trimester uterine artery Doppler studies will detect 50-65% of women who will develop severe preeclampsia (i.e. needing delivery before 35 weeks). Measurement of placental volume with three-dimensional ultrasound at 11-14 weeks detected 20% for a false positive rate of 10% in one study and further evaluation of this technique is needed. Maternal serum placental growth factor, vascular endothelial growth factor and soluble fms-like tyrosine kinase-1 have shown initial promise, but recent studies have shown no improvement in screening compared with using uterine artery Doppler alone. Placental protein 13 is the most promising serum marker and in combination with uterine Doppler may predict up to 90% of cases of severe preeclampsia for a false positive rate of 9%. SUMMARY: First-trimester uterine artery Doppler can identify over half of women who will develop preeclampsia. Detection rates may be increased by a combination of uterine artery Doppler with first-trimester maternal serum markers, especially placental protein 13. Such high-risk women may be the most likely to benefit from pharmacological intervention in future trials.
Biomarkers↗
A link between high serum levels of human chorionic gonadotrophin and chorionic expression of its mature functional receptor (LHCGR) in Down's syndrome pregnancies.
Human chorionic gonadotrophin (hCG) is released from placental trophoblasts and is involved in establishing pregnancy by maintaining progesterone secretion from the corpus luteum. Serum hCG is detected in the maternal circulation within the first 2-3 wks of gestation and peaks at the end of the first trimester before declining. In Down's syndrome (DS) pregnancies, serum hCG remains significantly high compared to gestation age-matched uncompromised pregnancies. It has been proposed that increased serum hCG levels could be due to transcriptional hyper-activation of the CGB (hCG beta) gene, or an increased half life of glycosylated hCG hormone, or both. Another possibility is that serum hCG levels remain high due to reduced availability of the hormone's cognate receptor, LHCGR, leading to lack of hormone utilization. We have tested this hypothesis by quantifying the expression of the hCG beta (CGB) RNA, LHCGR RNA and LHCGR proteins in chorionic villous samples. We demonstrate that chorionic expression of hCG beta (CGB) mRNA directly correlates with high serum hCG levels. The steady-state synthesis of LHCGR mRNA (exons 1-5) in DS pregnancies was significantly higher than that of controls, but the expression of full-length LHCGR mRNA (exons 1-11) in DS was comparable to that of uncompromised pregnancies. However, the synthesis of high molecular weight mature LHCGR proteins was significantly reduced in DS compared to uncompromised pregnancies, suggesting a lack of utilization of circulating hCG in DS pregnancies.
Animals↗
Placental expression of interferon-gamma (IFN-gamma) and its receptor IFN-gamma R2 fail to switch from early hypoxic to late normotensive development in preeclampsia.
The inability of the mother to switch from T helper cell type 1 (Th1) to Th2 cytokine profiles at the fetal-maternal interface has been proposed as one of the primary causes of miscarriage, intrauterine growth restriction (IUGR), and preeclampsia (PE). The Th1 [interferon-gamma (IFN-gamma), TNF-alpha, and IL-12] and Th2 (IL-4 and IL-10) cytokines have opposite effects on human pregnancy. Leukemia inhibitory factor (LIF) promotes embryo implantation and sustains pregnancy, whereas IFN-gamma and TNF-alpha are detrimental to pregnancy. Both IFN-gamma and LIF are produced by maternal cells and tissues at the fetal-maternal interface, whereas the IFN-gamma receptors (IFN-gamma R1 and IFN-gamma R2) and LIF receptor are abundantly expressed on the surface of placental trophoblasts. The effect of IFN-gamma on T lymphocyte activation is influenced by the relative membrane density of its two receptors, particularly IFN-gamma R2. In this study we report that in PE (25-40 wk gestation) and PE complicated by IUGR, IFN-gamma R2 protein expression is severely down-regulated and is similar to that observed in early placenta (7-10 wk gestation) developing under low O(2) tension. IFN-gamma production was found to be inversely related to the IFN-gamma R2 protein expression, and LIF receptor protein expression in PE mimicked that in early placental development. These results show that in PE, placental trophoblasts fail to establish an early to late switch with respect to IFN-gamma and IFN-gamma R2 expression. This supports the hypothesis that trophoblasts control the polarization of maternal immune effectors and cytokine profiles at the fetal-maternal interface that could be subject to oxidative stress in PE.
Base Sequence↗
Comparison of follicular vascularization in normal versus polycystic ovaries during in vitro fertilization as measured using 3-dimensional power Doppler ultrasonography.
OBJECTIVE: The growth of the follicles induced by gonadotropins during IVF treatment is accompanied by physiologic angiogenesis, which is essential for the maturation of the oocytes. We describe the IVF-induced changes in the vascularization and compare normal with polycystic ovaries (PCOs). DESIGN: Prospective study. SETTING: Assisted reproductive unit at a university hospital. PATIENT(S): Sixty women who underwent IVF cycles. INTERVENTION(S): The ovarian vascularization was measured after pituitary down-regulation, FSH stimulation, and hCG-injection using three-dimensional power Doppler ultrasonography. MAIN OUTCOME MEASURE(S): The total ovarian vascularization was divided by the number of follicles. RESULT(S): After pituitary suppression, the ovarian vascularization/follicle was lower in polycystic ovary (PCO) patients. During ovarian stimulation, follicles in PCOs required a lesser amount of FSH to acquire the same level of vascularization than the follicles in normal ovaries. In addition, hCG induced an increase in the follicular vascularization in both normal and PCOs. The follicle count correlated with the total vascularized volume in the ovaries throughout the IVF cycle. CONCLUSION(S): Follicles in PCOs seem to be less vascularized than the follicles in normal ovaries after GnRH treatment but not after gonadotropin stimulation. It is possible that restricted blood supply to the follicles in PCO might be associated with the follicular arrest that is observed. We could confirm that follicles in PCO are more sensitive to gonadotropin stimulation than follicles in normal ovaries.
Adult↗
Temporal regulation of the expression of syncytin (HERV-W), maternally imprinted PEG10, and SGCE in human placenta.
Maternally imprinted PEG10 and SGCE, separated by approximately 2.15 Mb from Syncytin (HERV-W) gene at 7q21.3, are implicated in choriocarcinoma and Silver-Russell syndrome. Here we have analyzed the temporal regulation of mRNA expression of these genes in placenta and demonstrate that Syncytin gene activation is highest in term placenta, PEG10, downregulated at early hypoxic phase, and highly activated at 11-12 wk of gestation. In contrast, transcription from SGCE remained unchanged throughout pregnancy, suggesting two neighboring imprinted genes are differentially regulated at very early pregnancy. Additionally, accumulation of two major species of mRNA (8 kb and 3.1 kb) encoded by HERV-W in placenta is regulated: 3.1 kb mRNA level remained unchanged throughout pregnancy, whereas the production of 8 kb species was highest in term placenta. Western blot and immunohistochemical staining of placental tissues with monoclonal antibodies revealed a marked reduction of syncytin glycoprotein synthesis in late pregnancy. Therefore, the relative levels of 3.1 kb and 8 kb mRNAs in trophoblasts could regulate syncytin protein synthesis, possibly by competition of the two mRNA species for translational apparatus.
Apoptosis Regulatory Proteins↗
Side of ovulation and its effects on uterine and ovarian stromal blood flow and reproductive hormones.
OBJECTIVE: Effect of the side of ovulation on uterine, ovarian, and follicular blood flow parameters and various hormone levels. DESIGN: Prospective, observational study. SETTING: Fertility Clinic, St. George's Hospital. PATIENT(S): Nineteen women with regular menstrual cycles. Pulsed Doppler measurements and serum hormonal concentrations during midfollicular, periovulatory, and midluteal phase for three successive cycles. MAIN OUTCOME MEASURE(S): Doppler blood flow and serum hormones. RESULT(S): Doppler blood flow of the ovarian stroma and follicular and uterine arteries showed no differences in the three phases between the right and left sides. Left-side uterine peak systolic velocity (PSV) (right-side PSV, 31.51cm/s; left-side PSV, 37.38 cm/s) during the periovulatory phase tended to be higher in the nondominant ovary; however, this was not quite significant. The serum hormone concentration showed no significant differences. CONCLUSION(S): The side of ovulation did not influence the Doppler blood flow to the ovarian stroma or follicular and uterine arteries. The side of ovulation had no effect on serum FSH, LH, 17beta-estradiol, P, inhibin A, or inhibin B levels.
Adult↗
Effect of pituitary down-regulation on the ovary before in vitro fertilization as measured using three-dimensional power Doppler ultrasound.
OBJECTIVE: To evaluate the changes taking place in the ovaries during pituitary down-regulation. DESIGN: Prospective observational study of women undergoing IVF treatment. SETTING: A tertiary referral center for assisted reproduction. PATIENT(S): Forty women who received the long buserelin acetate treatment protocol. Transvaginal three-dimensional power Doppler ultrasound examinations before and after pituitary down-regulation. INTERVENTION(S): Ovarian volume, number of follicles, vascularization index (VI), flow index (FI), vascularization flow index (VFI), and mean gray value (MG). RESULT(S): Before the pituitary down-regulation, the dominant ovary was larger in volume and had a lower MG than the nondominant ovary. After the down-regulation, there was a significant decrease in the volume and number of follicles and an increase in MG. After pituitary down-regulation, the dominant and nondominant ovaries did not differ from each other in any of the parameters. Polycystic ovaries were larger than normal ones before and after the down-regulation, without any differences in MG, VI, FI, or VFI. Right and left ovaries did not differ from each other after the down-regulation. CONCLUSION(S): The differences observed between dominant and nondominant ovaries seem to disappear after pituitary down-regulation. In addition, polycystic ovaries were always larger than the normal ones, but no differences could be detected in the stromal brightness or vascularity either before or after the administration of GnRH agonist therapy.
Buserelin↗
Quantification of ovarian power Doppler signal with three-dimensional ultrasonography to predict response during in vitro fertilization.
OBJECTIVE: To evaluate whether power Doppler predicts ovarian response to gonadotrophin stimulation during in vitro fertilization (IVF). METHODS: Forty-five women were divided into low-reserve (n = 12) and normal-reserve (n = 33) ovarian groups, according to antral follicle count. Transvaginal three-dimensional power Doppler ultrasonographic examinations were performed after pituitary downregulation and after gonadotrophin stimulation. The antral follicle count, ovarian volume, vascularization index, flow index, vascularization flow index, and mean gray value were measured and related to the number of oocytes retrieved and the pregnancy rate. RESULTS: The number of oocytes retrieved correlated with the antral follicle count (R =.458, P =.004) and ovarian volume (R =.388, P <.016) but not with vascularization index, flow index, vascularization flow index, or mean gray value after pituitary suppression. There was an increase in vascularization index (P <.017), flow index (P <.001), and vascularization flow index (P <.007) during gonadotrophin stimulation in the normal-ovary group but not in the low-ovarian-reserve group. CONCLUSION: According to our results, quantification of power Doppler signal in the ovaries after pituitary suppression does not provide any additional information to predict the subsequent response to gonadotrophin stimulation during IVF. The increase in ovarian power Doppler signal during gonadotrophin stimulation is related to the antral follicle count observed after pituitary suppression.
Adult↗
4D, or not 4D: that is the question.
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Female↗
Gene-specific chromatin damage in human spermatozoa can be blocked by antioxidants that target mitochondria.
Incubation of gradient purified human spermatozoa, which are routinely maintained in media prior to IVF and intracytoplasmic sperm injection (ICSI), induced DNA strand breaks (up to 89 nicks x 10(-3) bp) and chromatin release. Unlike highly dispersed Alu repeat sequences, the centromeric heterochromatin was much less susceptible to endonuclease attack. In addition to chromatin release, the permeability of the sperm membrane was altered as evidenced by reduced accessibility of sperm nuclei to decondensation factors in mouse embryo extracts. Hybridization of cDNA microarrays with DNA released from spermatozoa revealed a consistent hypersensitivity of certain genes to endogenous cleavage including TP53, VHL (tumour suppressors), BRCA1 (breast cancer), NOS1 (neurotransmitter), PECAM1, FLT1 (angiogenesis) and CDKN1C (cell cycle/imprinted). N-tert-butyl hydroxylamine (NTBH), a derivative of the anti-teratogenic alpha-phenyl-N-t-butyl nitrone (PBN) and synthetic superoxide dismutase (SOD)/catalase mimetics inhibited chromatin release and sustained or dissipated relative mitochondrial membrane potential. Together, these results show a link between the hyperactivation of sperm mitochondria and chromosomal damage of specific genes in vitro, and that the potential risk of disruption of paternally contributed genes can be circumvented by antioxidants which are known to target mitochondria.
Alu Elements↗