Giulia Bordi

The influence of endocrine disruptors in a selected population of infertile women

Abstract Several studies report that endocrine disrupting chemicals (EDC) able to interfere with endocrine homeostasis may affect women’s reproductive health. We analyzed EDC serum levels and nuclear receptors (NRs) expression in order to have an indication of the internal dose of biologically active compounds and a measurement of indicators of their effects, as a result of the repeated uptake from environmental source. The percentage of patients with detectable bisphenol A (BPA) concentrations was significantly higher in the infertile patients compared with fertile subjects. No significant difference was found between the groups with regard to perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), mono-ethylhexyl phthalate (MEHP) and di-(2-ethylhexyl) phthalate (DEHP) concentrations. Among infertile women, the mean expression of estrogen receptor alpha (ERα) and beta (Erβ), androgen receptor (AR) and pregnane X receptor (PXR) was significantly higher than fertile patients. The mean expression of aryl hydrocarbon receptor (AhR) and peroxisome proliferator-activated receptor gamma (PPARγ) did not show significant differences between two groups. Patients with endometriosis had higher levels of PPARγ than all women with other causes of infertility. This study led further support to EDC exposure as a risk factor for women’s fertility.

The influence of cigarette smoking on a population of infertile men and women

PurposeThis study aimed at investigating the effect of cigarette smoking on semen parameters in infertile men and on antral follicle count (AFC) and reproductive hormone levels in infertile women.MethodsIn 648 men (200 smokers and 448 non-smokers) sperm concentration, motility and morphology were compared according to smoking status. In the female population, AFC and basal follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol were measured in 296 women (102 smokers and 194 non-smokers). Statistical analysis of data was performed using t test, χ²-test and Spearman’s correlation.ResultsAmong the male population, smokers had significantly lower sperm concentration and motility than non-smokers. Sperm normal morphology was reduced in smokers, although this difference did not reach statistical significance. No significant correlation was found between sperm parameters and the intensity of smoking. In the female population, AFC was reduced in smokers compared with non-smokers. Women who smoked had significantly higher FSH levels. No significant difference was found in LH and estradiol levels according to smoking status. The number of pack-years was negatively correlated to AFC and positively correlated to FSH levels.ConclusionCigarette smoking is associated with damaging effects on sperm parameters in infertile men and with ovarian reserve alteration in infertile women, as reflected by reduced AFC and increased FSH levels. Every smoker should be encouraged to stop smoking to prevent the damage of the toxins contained in cigarette smoking and preserve their own reproductive potential.

Maternal and perinatal outcomes in spontaneous versus assisted conception twin pregnancies

OBJECTIVE To compare maternal and perinatal outcomes in twin pregnancies conceived via assisted reproductive techniques (ART) compared with spontaneous twin pregnancies. STUDY DESIGN This retrospective study examined 345 dichorionic, di-amniotic twin pregnancies (207 conceived spontaneously and 138 conceived via ART), delivered between January 2007 and June 2011 at the San Pietro Fatebenefratelli Hospital, Rome, a tertiary medical centre. Maternal and perinatal outcomes were compared. A multiple logistic regression analysis was performed to calculate risk estimates as odds ratios (OR) adjusted for maternal age, parity and systemic diseases. Patient data were obtained from a computerized database and analyzed using Statistical Package for the Social Sciences Version 17. RESULTS Gestational age and birth weight were lower in the ART group, and preterm delivery, gestational diabetes and placental abruption were higher in the ART group compared with the spontaneous conception group. The incidence rates of respiratory complications, patent ductus arteriosus and admission to the neonatal intensive care unit were higher among ART newborns. Length of hospital stay for mothers and newborns was longer in the ART group. No differences in mode of delivery, Apgar score at 5min, congenital anomalies, perinatal mortality, and other considered pregnancy and neonatal complications were found between the two groups. Multivariate analysis adjusted for maternal age, parity and systemic diseases revealed that only the rates of placental abruption [OR 7.45, 95% confidence interval (CI) 2.05-26.98] and patent ductus arteriosus (OR 3.39, 95% CI 1.01-11.46) were significantly higher for the ART group. CONCLUSIONS Twin pregnancies conceived via ART are at greater risk of poorer outcomes than spontaneous twin pregnancies. This may be related to the type of conception and specific negative features of subfertile patients undergoing infertility treatment.

Correlation of Endocrine Disrupting Chemicals Serum Levels and White Blood Cells Gene Expression of Nuclear Receptors in a Population of Infertile Women

Significant evidence supports that many endocrine disrupting chemicals could affect female reproductive health. Aim of this study was to compare the internal exposure to bisphenol A (BPA), perfluorooctane sulphonate (PFOS), perfluorooctanoic acid (PFOA), monoethylhexyl phthalate (MEHP), and di(2-ethylhexyl) phthalate (DEHP) in serum samples of 111 infertile women and 44 fertile women. Levels of gene expression of nuclear receptors (ERα, ERβ, AR, AhR, PXR, and PPARγ) were also analyzed as biomarkers of effective dose. The percentage of women with BPA concentrations above the limit of detection was significantly higher in infertile women than in controls. No statistically significant difference was found with regard to PFOS, PFOA, MEHP and DEHP. Infertile patients showed gene expression levels of ERα, ERβ, AR, and PXR significantly higher than controls. In infertile women, a positive association was found between BPA and MEHP levels and ERα, ERβ, AR, AhR, and PXR expression. PFOS concentration positively correlated with AR and PXR expression. PFOA levels negatively correlated with AhR expression. No correlation was found between DEHP levels and all evaluated nuclear receptors. This study underlines the need to provide special attention to substances that are still widely present in the environment and to integrate exposure measurements with relevant indicators of biological effects.

Exposure to Endocrine Disrupters and Nuclear Receptor Gene Expression in Infertile and Fertile Women from Different Italian Areas

Within the PREVIENI project, infertile and fertile women were enrolled from metropolitan, urban and rural Italian areas. Blood/serum levels of several endocrine disrupters (EDs) (perfluorooctane sulfonate, PFOS; perfluorooctanoic acid, PFOA; di-2-ethylhexyl-phthalate, DEHP; mono-(2-ethylhexyl)-phthalate, MEHP; bisphenol A, BPA) were evaluated concurrently with nuclear receptors (NRs) gene expression levels (ERα, ERβ, AR, AhR, PPARγ, PXR) in peripheral blood mononuclear cells (PBMCs). Infertile women from the metropolitan area displayed significantly higher levels of: BPA compared to fertile women (14.9 vs. 0.5 ng/mL serum); BPA and MEHP compared to infertile women from urban and rural areas; enhanced expression levels of NRs, except PPARγ. Infertile women from urban and rural areas had PFOA levels significantly higher than those from metropolitan areas. Our study indicates the relevance of the living environment when investigating the exposure to EDs and the modulation of the NR panel in PBMC as a suitable biomarker of the effect, to assess the EDs impact on reproductive health.

Exposure to endocrine disruptors and nuclear receptors gene expression in infertile and fertile men from Italian areas with different environmental features

Internal levels of selected endocrine disruptors (EDs) (i.e., perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), di-2-ethylhexyl-phthalate (DEHP), mono-(2-ethylhexyl)-phthalate (MEHP), and bisphenol A (BPA)) were analyzed in blood/serum of infertile and fertile men from metropolitan, urban and rural Italian areas. PFOS and PFOA levels were also evaluated in seminal plasma. In peripheral blood mononuclear cells (PBMCs) of same subjects, gene expression levels of a panel of nuclear receptors (NRs), namely estrogen receptor α (ERα) estrogen receptor β (ERβ), androgen receptor (AR), aryl hydrocarbon receptor (AhR), peroxisome proliferator-activated receptor γ (PPARγ) and pregnane X receptor (PXR) were also assessed. Infertile men from the metropolitan area had significantly higher levels of BPA and gene expression of all NRs, except PPARγ, compared to subjects from other areas. Subjects from urban areas had significantly higher levels of MEHP, whereas subjects from rural area had higher levels of PFOA in both blood and seminal plasma. Interestingly, ERα, ERβ, AR, PXR and AhR expression is directly correlated with BPA and inversely correlated with PFOA serum levels. Our study indicates the relevance of the living environment when investigating the exposure to specific EDs. Moreover, the NRs panel in PBMCs demonstrated to be a potential biomarker of effect to assess the EDs impact on reproductive health.

The effect of maternal exposure to endocrine disrupting chemicals on fetal and neonatal development: A review on the major concerns.

There is a widespread exposure of general population, including pregnant women and developing fetuses, to the endocrine disrupting chemicals (EDCs). These chemicals have been reported to be present in urine, blood serum, breast milk, and amniotic fluid. Endocrine disruptions induced by environmental toxicants have placed a heavy burden on society, since environmental exposures during critical periods of development can permanently reprogram normal physiological responses, thereby increasing susceptibility to disease later in life-a process known as developmental reprogramming. During development, organogenesis and tissue differentiation occur through a continuous series of tightly-regulated and precisely-timed molecular, biochemical, and cellular events. Humans may encounter EDCs daily and during all stages of life, from conception and fetal development through adulthood and senescence. Nevertheless, prenatal and early postnatal windows are the most critical for proper development, due to rapid changes in system growth. Although there are still gaps in our knowledge, currently available data support the urgent need for health and environmental policies aimed at protecting the public and, in particular, the developing fetus and women of reproductive age. Birth Defects Research (Part C) 108:224-242, 2016.

Levels of Galectin-3 and Stimulation Expressed Gene 2 in the peritoneal fluid of women with endometriosis: a pilot study

Abstract Endometriosis is a puzzling disorder with obscure pathogenesis. Several studies suggest that peritoneal fluid is a key inflammatory environment in the development and progression of the disease. This study analyzed the levels of two inflammatory factors – Galectin-3 and Stimulation Expressed Gene 2 – in the peritoneal fluid of 15 women affected by endometriosis and 8 controls. The peritoneal fluid was collected during laparoscopic surgery avoiding any form of contamination and it was properly processed and stored. Gal-3 and ST2 peritoneal concentrations were analyzed using enzyme immunoassay kit. Gal-3 levels were significantly higher in endometriosis group than in controls (64.7 ± 52.34 versus 21.05 ± 20.83 ng/ml, p = 0.044), whereas ST2 concentrations did not differ between the two groups. A significant positive correlation was found between Gal-3 and ST2 levels. Gal-3 levels positively correlated with the stage of endometriosis, the duration of symptoms, Marinoff scale and VAS score, while ST2 levels were positively associated with VAS score. Our results suggest that Gal-3 and ST2 could be implicated in the inflammatory process of the disease. Further studies are needed to identify markers of early diagnosis and to open new therapeutic avenues in endometriosis. Chinese abstract 由于并未明确的发病机制,子宫内膜异位症成为一种令人困惑的疾病。一些研究认为腹腔液是子宫内膜异位发生和发展的关键炎症环境。本研究分析了两种炎症因子-- 半乳糖凝集素3及刺激表达基因2在15名患有子宫内膜异位症妇女和8名对照妇女腹腔液中的水平。腹腔液通过避免了任何污染的腹腔镜手术收集并妥善处理和保存，随后使用酶免疫分析法分析了浓缩腹腔液中的Gal-3和ST2。异位症组的Gal-3水平明显高于对照组(64.7 ± 52.34 比 21.05 ± 20.83 ng/ml,p=0.044)，而ST2水平在两组中并无明显差异。Gal-3与ST2水平存在明显的正相关，Gal-3水平与内异症的发展阶段、症状的持续时间、Marinoff及VAS评分正相关，而ST2与VAS评分呈正相关。我们的结果显示Gal-3和ST2或与内异症炎症发展过程有关。为确定子宫内膜异位症的早期诊断标记物及开展新的治疗方式仍需要进一步的研究。

The Influence of Socio-Demographic Factors on Miscarriage Incidence Among Italian and Immigrant Women: A Critical Analysis from Italy

Abstract Miscarriage is one of the most relevant adverse events in women’s reproductive life. The purpose of the study was to describe miscarriage trend in Italy during the last years among Italian and immigrant women, to compare miscarriage rates of the two groups and to evaluate the effect of age, nationality and educational level on the incidence of having a miscarriage. Then, a brief critical review of other miscarriage risk factors was performed. This study is based on ISTAT database. All data were analyzed through the statistical software SPSS and the following analytical techniques were used: multivariate logistic regression, factorial analysis of variance and Chi square test. Immigrant miscarriage rates resulted higher than Italian ones and they decreased from 2003 to 2009 unlike Italian ones, which remained unchanged. The effect of maternal age on the miscarriage incidence resulted different, depending on the nationality; for Italian women it increased with increasing of age and for immigrant women the opposite trend was found. Moreover, miscarriage incidence resulted significantly different depending on the maternal educational level. Whereas immigrant women considered did not belong to the same ethnic group, biological or genetic factors underlying these differences were excluded and a socioeconomic explanation was provided. Finally, in order to provide more complete information, other miscarriage risk factors were discussed through a brief review of the literature.

Study of a Population of Triplet Pregnancies: Maternal and Neonatal Outcomes

Objective: To describe maternal complications, perinatal mortality and neonatal morbidity in triplet pregnancies. Methods: Retrospective analysis of maternal and neonatal records of 21 triplet pregnancies delivered from January 2008 to June 2011 at San Pietro FBF Hospital of Rome, a tertiary medical center. Results: The incidence of triplet pregnancies was one in 690 births. Among the 21 triplet pregnancies, only one was conceived spontaneously and 20 were the result of assisted reproductive techniques. Mean maternal age was 34.4 ± 5 years. There was one case of a selective foeticide of a foetus with an encephalocele. Preterm delivery occurred in all the remaining 20 pregnancies. Other frequent complications were premature rupture of membranes (40%) and cervical incompetence (35%). There was no maternal mortality in any of the studied pregnancies. The mean length of maternal hospitalization was 15 ± 5.9 days. The mean gestational age was 31.8 weeks, with a mean birth weight of 1590 ± 590 grams. The neonatal mortality was 5%. The incidence of congenital anomalies was 16.7%. Respiratory distress syndrome occurred in 53% of cases and 75.6% of newborns required intensive care. Other common neonatal complications were jaundice (66.7%), anaemia (28.9%), patent ductus arteriosus (24.4%), apnea of prematurity (17.8%), sepsis (13.3%), neurological complications (11.1%) and bronchopulmonary dysplasia (11.1%). The mean length of newborns hospitalization was 33.6 ± 23.3 days. There was no significant difference in neonatal mortality and morbidity based on birth order. Conclusions: This series of triplet pregnancies demonstrated an excellent survival rate and a relatively low major morbidity, despite the 100% incidence of prematurity. Although perinatal outcomes in triplet gestations have improved in recent years, higher-order multiple pregnancies continued to be associated with great medical problems for both mothers and infants. All methods of assisted reproduction should aim for the prevention of multifetal pregnancies.