Piergiorgio Stortoni

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.

Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

Uterine leiomyomas (fibroids or myomas) are benign tumors of uterus and clinically apparent in a large part of reproductive aged women. Clinically, they present with a variety of symptoms: excessive menstrual bleeding, dysmenorrhoea and intermenstrual bleeding, chronic pelvic pain, and pressure symptoms such as a sensation of bloatedness, increased urinary frequency, and bowel disturbance. In addition, they may compromise reproductive functions, possibly contributing to subfertility, early pregnancy loss, and later pregnancy complications. Despite the prevalence of this condition, myoma research is underfunded compared to other nonmalignant diseases. To date, several pathogenetic factors such as genetics, microRNA, steroids, growth factors, cytokines, chemokines, and extracellular matrix components have been implicated in the development and growth of leiomyoma. This paper summarizes the available literature regarding the ultimate relative knowledge on pathogenesis of uterine fibroids and their interactions with endometrium and subendometrial myometrium.

The involvement of inflammatory cytokines in the pathogenesis of recurrent miscarriage.

OBJECTIVE To investigate the inflammatory cytokine expression pattern in trophoblastic tissue from women with unexplained recurrent miscarriage (RM). STUDY DESIGN Trophoblasts were obtained during uterine evacuation from 11 women with RM and from 20 healthy pregnant women undergoing elective termination of pregnancy, who served as controls. The array was performed using GEArray Q Series Human Inflammatory Cytokines & Receptors Gene Array HS-015 membranes. Data were confirmed by quantitative real-time PCR. The Mann-Whitney U test was performed for statistical analysis. RESULTS Microarray analysis identified three genes that were differentially expressed between RM patients and controls. We observed significant downregulation of Transforming Growth Factor beta 3 (TGF-β3) and Interleukin 25 (IL-25) (5-fold reduction and 2.5-fold reduction, respectively) and significant upregulation of CD-25, also known as Interleukin 2 receptor alpha (IL-2RA) (7-fold increase) in women with RM compared with controls. The median ΔC(t) of TGF-β3 was 8.2 (interquartile range, 7.67-8.9) in RM patients vs. 5.85 (interquartile range, 5.3-6.09) in controls; the median ΔC(t) of IL-25 was 5.18 (interquartile range, 4.46-5.76) in RM patients vs. 3.85 (interquartile range, 3.6-4.51) in controls, and the median ΔC(t) of CD-25 was 9.62 (interquartile range, 7.81-12.42) in RM patients vs. 12.44 (interquartile range, 11.02-13.86) in controls. DISCUSSION Our results suggest that the immunological and inflammatory regulation mechanisms of the placental environment play a key role in recurrent miscarriage. The observed trophoblast cytokine expression pattern at the maternal-fetal interface confirms the immunotrophic theory, as demonstrated by a switch from a T-helper-1 (Th1) profile to a T-helper-2 (Th2) profile in women who experience recurrent miscarriages.

The impact of loop electrosurgical excision procedure (LEEP) for CIN 2,3 on spontaneous preterm delivery in twin pregnancies by assisted reproductive technique: preliminary data

Abstract The objective of this study was to compare the frequency of spontaneous preterm delivery before 35 weeks in 7 dichorionic twin pregnancies obtained after loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) 2,3 with respect to 21 twin pregnancies without previous cervical treatment. All the pregnancies were obtained after assisted reproduction techniques (ART). Same age at delivery was observed between two groups (p = 0.81) and none of our twin pregnancies after LEEP had a threatened preterm labor while four controls (19%) underwent a spontaneous preterm delivery (p = 0.35). These preliminary data seem to indicate that LEEP may not be responsible of spontaneous preterm delivery in twin pregnancies subsequent to ART.

Clues to apoptosis pathway involvement in hemolysis, elevated liver enzyme, and low platelet (HELLP) syndrome and intrauterine growth restriction (IUGR)

Objective: The neurotrophin family comprises molecules involved in growth, differentiation, survival, regeneration, normal functions of the neuronal system, and in angiogenesis. We have investigated the expression pattern of neurotrophic signaling molecules in pregnancies complicated by elevated liver enzyme, and low platelet (HELLP) syndrome and intrauterine growth restriction (IUGR). Methods: Placentas from normal and pathological pregnancies were collected. Macroarray analysis was performed and the data were confirmed by real-time PCR. Results: Real-time PCR analyses (pathological vs. normal pregnancies) confirmed a significant down-regulation for IL-6, STAT3α, STAT3β, and Bcl-2. The expression of Mcl-1 isoform 1 (long) was significantly increased. Conclusions: We suggest that decreased expression of IL-6 could mean that abnormalities in the immunological system function involve inflammatory cytokines other than IL-6 in examined pathological pregnancies. The STAT3α and STAT3β down-regulation lead to a marked reduction of cellular transcriptional activity. Decreased expression of IL-6 is associated with a down-regulation of Bcl-2 but not of Mcl-1 isoform 1, suggesting that these two antiapoptotic proteins may function independently and that Mcl-1 may have a distinct role in controlling apoptotic pathway.

Hypothyroidism, Fertility and Pregnancy

Pregnancy has a profound effect on the thyroid gland and its function. In iodine-replete countries, the gland size has been found to increase by 10% during pregnancy, and in areas of iodine deficiency, the gland size increases by 20%–40%. The prevalence of hypothyroid‐ ism during pregnancy is estimated to be 0.3–0.5% for overt hypothyroidism and 2–3% for subclinical hypothyroidism. Worldwide, iodine deficiency remains one of the leading causes of both overt and subclinical hypothyroidism. However, there are many other causes of hy‐ pothyroidism during pregnancy, including autoimmune thyroiditis, the most common or‐ ganic pathology [1]. Other causes include the following: thyroid radioiodine ablation (to treat hyperthyroidism or thyroid cancer), hypoplasia and/or agenesis of the thyroid gland, surgery (for thyroid tumors and, rarely, central hypothyroidism, including lymphocytic hy‐ pophysitis or ectopic thyroid) and some drugs, such as rifampin and phenytoin, which can alter thyroid metabolism [2].