Angelo Turi

Placental thrombomodulin expression in recurrent miscarriage

BackgroundEarly pregnancy loss can be associated with trophoblast insufficiency and coagulation defects. Thrombomodulin is an endothelial-associated anticoagulant protein involved in the control of hemostasis and inflammation at the vascular beds and its also a cofactor of the protein C anticoagulant pathway.DiscussionWe evaluate the Thrombomodulin expression in placental tissue from spontaneous recurrent miscarriage and voluntary abortion as controls. Thrombomodulin mRNA was determined using real-time quantitative polymerase chain reaction. Reduced expression levels of thrombomodulin were found in recurrent miscarriage group compared to controls (1.82-fold of reduction), that corresponds to a reduction of 45% (from control group Delta CT) of thrombomodulin expression in spontaneous miscarriage group respect the control groups.SummaryWe cannot state at present the exact meaning of a reduced expression of Thrombomodulin in placental tissue. Further studies are needed to elucidate the biological pathway of this important factor in the physiopathology of the trophoblast and in reproductive biology.

Partner support and postpartum depressive symptoms.

Background: One out of eight women suffers an episode of depression following delivery. We explored the role of expectations of partner support in postpartum depressive symptoms in new mothers attending a regional public hospital in Italy. Methods: Seventy women participated in a two-stage (third trimester and 3 months postpartum) prospective study using self-report measures. At stage 1, they completed the Support Expectations Index to measure expectations for partner support and the Dyadic Adjustment Scale to measure conflicts in marital relationship, whereas socio-demographic (i.e. maternal age and education level) and clinical variables (i.e. previous miscarriages and depression episodes) were collected from medical reports. Depressive symptoms were evaluated at stage 2 with the Edinburgh Postnatal Depression Scale using a cut-off >9 and confirmation of marital support expectations was measured with the Expectancy Confirmation Scale. Stepwise logistic regression analysis was used to examine predictors of depressive symptoms at 3 months postpartum. Results and discussion: As many as 55.7% (n = 39) of new mothers presented postpartum depressive symptoms, which were predicted by low expectancy confirmation concerning partner support [odds ratio (OR) 3.02; 95% confidence interval (CI) 1.25–8.10]. Therefore, clinicians should consider the possible role of partner support when treating women with postnatal depressive symptoms.

Preconception Steroid Treatment in Infertile Women with Antithyroid Autoimmunity Undergoing Ovarian Stimulation and Intrauterine Insemination: A Double-Blind, Randomized, Prospective Cohort Study

OBJECTIVE This study investigated the role of a steroid pretreatment on the pregnancy rate and pregnancy outcomes in patients positive for antithyroid antibodies who were undergoing induction of ovulation and intrauterine insemination (IUI). METHODS A double-blind, randomized, prospective cohort study was conducted on infertile women who met the following criteria: infertility for ≥ 1 year, age 20-38 years, no more than 2 previous assisted reproduction treatment cycles, regular spontaneous menstrual cycles, no treatments 1 month before recruitment, normal uterine cavity, and bilateral tubal patency. The patients were divided into 2 groups: a study group of infertile women with antithyroid autoimmunity (radioimmunoassay positive with titer >100 U/mL) and a control group of infertile women without antithyroid autoimmunity. The patients with antithyroid autoimmunity were randomly assigned in a blinded manner to an intervention group treated with prednisone (administered orally for 4 weeks before IUI) or a group given matching placebo. The primary objective was to compare the pregnancy and miscarriage rates among all 3 the groups. RESULTS The study included 98 infertile women: 48 with antithyroid autoimmunity (antibody positive) and 50 without antithyroid autoimmunity (antibody negative). The study groups were comparable for baseline characteristics (age, race, body mass index, hormonal pattern, number of smokers, previous miscarriage). In the antithyroid antibody-positive group, the pregnancy rate was 33.3% (8/24) among women treated with prednisone compared with 8.4% (2/24) among women who received placebo (odds ratio [OR] = 5.5; 95% CI, 1.13-25.76; P = 0.03). In the antibody-negative group, the pregnancy rate was 8.0% (4/50). Among the pregnancies, the miscarriage rate was 70% (7/10) versus 75% (3/4) for women with or without antithyroid antibodies, respectively (P = NS); the miscarriage rate was 75% (6/8) for women treated with prednisone versus 50% (1/2) for women taking placebo (P = 0.49). No adverse effects were reported. CONCLUSIONS In this small cohort study of infertile women with antithyroid antibodies undergoing induction of ovulation and IUI, prophylactic therapy with prednisone was associated with a significantly higher rate of pregnancy compared with placebo. The miscarriage rate was not significantly different among the 3 groups.

Coenzyme Q10 content in follicular fluid and its relationship with oocyte fertilization and embryo grading

BackgroundNo data are available on the presence and content of Coenzyme Q10 (CoQ10) in human follicular fluid and its role.ObjectiveTo assess the presence and concentration of CoQ10 in human follicular fluid in relation to oocyte fertilization.MethodsCQ10 content was measured in follicular fluid obtained from 20 infertile women undergoing ovarian stimulation program for in vitro fertilization. CoQ10 levels were assayed by high-performance liquid chromatography system and normalized for follicular cholesterol and protein levels. Oocyte morphology and embryo grading were assessed.ResultsCoQ10/Protein levels resulted significantly in mature versus dysmorphic oocytes. Similarly, CoQ10/Cholesterol was significantly higher in grading I–II versus grading III–IV embryos.ConclusionsThis study is the first demonstration of the presence of CoQ10 in the human follicular fluid. Although the biological and endocrine mechanism of CoQ10 in the follicular fluid and its correlation with oocyte and embryo development is unclear, a new step may be the administration of CoQ10 in infertile women to evaluate the biological and reproductive outcomes.

Nitric oxide platelet production in spontaneous miscarriage in the first trimester

OBJECTIVE To investigate the role played by platelet nitric oxide (NO) metabolism in patients with spontaneous miscarriage (SM) and recurrent spontaneous miscarriage (RSM) compared with healthy pregnant women. DESIGN Retrospective case-control study. SETTING Patients and controls in an academic research environment. INTERVENTION(S) None. PATIENT(S) Thirty singleton pregnant women who experienced SM, nine singleton pregnant women who presented with RSM, and 30 singleton healthy pregnant women matched for age, parity, and gestational age were enrolled. MAIN OUTCOME MEASURE(S) NO levels and peroxynitrite (ONOO(-)) production; moreover, inducible NO synthase (iNOS), endothelial NO synthase (eNOS), and nitrotyrosine expression (N-Tyr) were observed in the same samples. RESULT(S) A significant increase was shown in platelet NO and ONOO(-) levels and in iNOS and N-Tyr both in SM and in RSM pregnant women compared with controls. CONCLUSION(S) The data herein reported imply that a modified NO pathway might play a key role in the physiological changes of advancing gestation but may also contribute to the pathophysiology of spontaneous miscarriage. Thus, any factors balancing NO metabolism might be useful in the treatment of miscarriage, thus reducing the substantial morbidity and associated mortality.

Placental Expression of CD100, CD72 and CD45 Is Dysregulated in Human Miscarriage

Context and Objective The etiology of miscarriage is often multifactorial. One major cause, immunological rejection of the fetus, has not been clearly elucidated. Our aim was to establish whether the semaphorin CD100, its natural receptor CD72, and the glycoprotein CD45, implicated in immune mechanisms, are involved in pregnancy loss by examining their placental expression with real-time PCR, immunohistochemistry and western blotting techniques. Patients Placenta tissue from 72 Caucasian women undergoing surgical uterine evacuation due to early spontaneous pregnancy loss between the 8th and 12th week of gestation was divided into four groups based on miscarriage number. Gestational age-matched placentas from 18 healthy women without a history of miscarriage undergoing voluntary pregnancy termination were the control group. Placenta from 6 Caesarean deliveries performed at 38–40 weeks of gestation was also studied. Results CD100, CD72 and CD45 were expressed in placenta and exhibited different mRNA and protein levels in normal pregnancy and miscarriage. In particular, protein levels were highly dysregulated around 10 weeks of gestation in first and second miscarriage placentas. The CD100 soluble form was produced and immediately shed from placental tissue in all samples. Conclusions Fetal CD100, CD72 and CD45 seem to play a role in miscarriage. The present data support the involvement of the fetal immune system in pregnancy maintenance as well as failure.

The effect of astaxanthin on the aging rat brain: Gender-related differences in modulating inflammation

BACKGROUND Astaxanthin (Ax) is a ketocarotenoid of the xanthophyll family with activities such as antioxidation, preservation of the integrity of cell membranes and protection of the redox state and functional integrity of mitochondria. The aim of this study was to investigate potential gender-related differences in the effect of Ax on the aging rat brain. RESULTS In females, interleukin 1 beta (IL1β) was significantly lower in treated rats in both cerebral areas, and in the cerebellum, treated animals also had significantly higher IL10. In males, no differences were found in the cerebellum, but in the hippocampus, IL1β and IL10 were significantly higher in treated rats. CONCLUSION These are the first results to show gender-related differences in the effect of Ax on the aging brain, emphasizing the necessity to carefully analyze female and male peculiarities when the anti-aging potentialities of this ketocarotenoid are evaluated. The observations lead to the hypothesis that Ax exerts different anti-inflammatory effects in female and male brains.

Modulation of syndecans in the uterus throughout the menstrual cycle: comparison between endometrium and myometrium

Immunohistochemistry and semiquantitative analysis were used to examine and compare the expression of syndecans 1-4 in the endometrium and myometrium throughout the menstrual cycle. Syndecans molecules show different temporal and spatial expression during the menstrual cycle, and the modulation of syn-2 expression is statistically significantly correlated to morphologic and functional changes of the endometrium, particularly in the periovulatory period.

Possible role of placental CD100, CD72 and CD45 molecules in human miscarriage

The precise mechanism for recurrent miscarriage is unclear. A lot of metabolic alterations are involved in the missed intercommunication between mother and its foetus, causing their reciprocal intolerance. The identification of new molecules involved in pregnancy loss represents the main objective of our study. We analysed the semaphorin CD100, its natural receptor CD72 and the glycoprotein CD45, physically and functionally associated to CD100 in the placental tissues from recurrent miscarriages by real-time PCR, western blotting and immunohistochemistry. Placental tissue was obtained during surgical uterine evacuation in 72 caucasian women with early spontaneous pregnancy loss between 8th and 12th week of gestation and classified in four groups defined as first, second, third and fourth miscarriages. Other two normal placental groups were recruited: a) first trimester placentas (n = 18), matched for gestational age with placentas from spontaneous pregnancy loss; b) third trimester placentas (n = 6) at 38-40 weeks of gestation. We demonstrated that CD72, CD45 and CD100 mRNA were detectable in placental tissues with different expression in normal and pathological conditions. In addition, we demonstrated that CD72 and CD45 molecules were expressed in foetal macrophages and that their protein levels were especially deregulated in first and second miscarriages at about 10 weeks of gestation. On the contrary, CD100 cleaved protein appeared to be absent in placenta. In conclusion, our findings underline a possible role for CD100, CD72 and CD45 molecules in recurrent miscarriages, showing an important foetal involvement in the occurring of pregnancy loss.