Effects of Endocrine-Disrupting Chemicals on Endometrial Receptivity and Embryo Implantation: A Systematic Review of 34 Mouse Model Studies.

Several available studies have already analyzed the systemic effects of endocrine-disrupting chemicals (EDCs) on fertile woman and neonatal outcomes, but little is still known in humans about the precise mechanisms of interference of these compounds with the endometrial receptivity. There is consistent evidence that continuous and prolonged exposure to EDCs is a risk factor for reduced fertility and fecundity in women. Preliminary studies on mammalian models provide robust evidence about this issue and could help gynecologists worldwide to prevent long term injury caused by EDCs on human fertility. In this systematic review, we aimed to systematically summarize all available data about EDC effects on blastocyst endometrial implantation. We performed a systematic review using PubMed®/MEDLINE® to summarize all in vivo studies, carried out on mice models, analyzing the molecular consequences of the prolonged exposure of EDC on the implantation process. 34 studies carried out on mouse models were included. Primary effects of EDC were a reduction of the number of implantation sites and pregnancy rates, particularly after BPA and phthalate exposure. Furthermore, the endometrial expression of estrogen (ER) and progesterone receptors (PR), as well as their activation pathways, is compromised after EDC exposure. Finally, the expression of the primary endometrial markers of receptivity (such as MUC1, HOXA10, Inn and E-cadherin) after EDC contact was analyzed. In conclusion EDC deeply affect blastocyst implantation in mouse model. Several players of the implantation mechanism are strongly influenced by the exposure to different categories of EDC.

Radiations and female fertility.

Hundreds of thousands of young women are diagnosed with cancer each year, and due to recent advances in screening programs, diagnostic methods and treatment options, survival rates have significantly improved. Radiation therapy plays an important role in cancer treatment and in some cases it constitutes the first therapy proposed to the patient. However, ionizing radiations have a gonadotoxic action with long-term effects that include ovarian insufficiency, pubertal arrest and subsequent infertility. Cranial irradiation may lead to disruption of the hypothalamic-pituitary-gonadal axis, with consequent dysregulation of the normal hormonal secretion. The uterus might be damaged by radiotherapy, as well. In fact, exposure to radiation during childhood leads to altered uterine vascularization, decreased uterine volume and elasticity, myometrial fibrosis and necrosis, endometrial atrophy and insufficiency. As radiations have a relevant impact on reproductive potential, fertility preservation procedures should be carried out before and/or during anticancer treatments. Fertility preservation strategies have been employed for some years now and have recently been diversified thanks to advances in reproductive biology. Aim of this paper is to give an overview of the various effects of radiotherapy on female reproductive function and to describe the current fertility preservation options.

Maternal exposure to endocrine disruptors and placental transmission: a pilot study.

Endocrine disruptors (EDs) are known to affect maternal and child health. The objective of our study was to identify the association between some of the most important endocrine-disruptive substances (perfluorooctane sulfonate [PFOS], perfluorooctanoic acid [PFOA], di2-ethylhexyl-phthalate [DEHP] and mono2-ethylhexyl-phthalate [MEHP]) and both pregnancy variability and birth outcomes. We measured the concentration of the EDs in maternal and cord blood samples of 29 mother-newborn pairs from the Pertini Hospital in Rome between March and June 2016. Each mother reported demographic, life style and diet information. We compared concentrations of the endocrine disruptors between mother and newborn, and among different molecules. We analyzed differences and trends of each ED substance according to the demography and diet information. PFOA levels in maternal blood showed a negative association with newborn weight. Concentration levels of PFOA in both maternal and cord blood of those with physiological progression of pregnancy were higher in than in those with pathological pregnancies. MEHP trend showed a positive association with maternal age. These results confirm the maternal-to-fetus transfer of EDs through the placenta and the impact that endocrine disruptors have on pregnancy and birth outcomes.

Hyperandrogenism in a postmenopausal woman: a rare case of ectopic adrenal cortical gland.

Most frequent causes of androgenic manifestation are Cushing's syndrome, PCO, benign and malignant androgen-secreting non adrenal tumors and iatrogenic hirsutism. Hyperplasia or neoplasms of ectopic adrenocortical gland are rare. We report a case of a 63-year old female with hirsutism and alopecia. Laboratory data highlighted increased levels of androgens. Diagnostic imaging revealed normal morphology of adrenocortical gland and ovaries. In view of the clinical picture and suspected diagnosis of extra-adrenal cause, she underwent bilateral salpingo-oophorectomy. Histologic examination showed an ectopic adrenal gland with adenoma in the ovarian and peri-ovarian tissue. At six months of follow up, the patients has no sign of hyperandrogenism. In case of hyperandrogenism in postmenopausal women and in the absence of the adrenocortical gland abnormality, ovarian origin should be considered in the differential diagnosis.

Endometrial tubal metaplasia in a young puerperal woman after breast cancer.

INTRODUCTION: Tamoxifen is the usual endocrine (anti-estrogen) therapy for hormone receptor-positive breast cancer in pre and post-menopausal women. Previous studies have suggested an increased prevalence of endometrial diseases after treatment with tamoxifen. CASE PRESENTATION: The authors report a case of 38-year-old woman with diagnosis of endometrial polyp and tubal metaplasia, during puerperium and after micropapillary ductal breast cancer surgery, 5 years of tamoxifen treatment, spontaneous pregnancy without complications and full-term vaginal delivery. CONCLUSION: Tamoxifen is a safe and reliable treatment of breast cancer, but data suggest an association with endometrial polyps, hyperplasia, metaplasia and carcinoma. One of the most common types of endometrial metaplasia is ciliated tubal metaplasia. It is generally known that endometrial tubal metaplasia is a benign disease. However studies propose endometrial tubal metaplasia to be a potential premalignant endometrial lesion and its association with endometrial hyperplasia and well-differentiated endometrioid carcinoma. We propose close monitoring of patients taking tamoxifen and prompt evaluation of any uterine bleeding or pelvic complaint or abnormal TVUS images.

Conservative and timely treatment in retained products of conception: a case report of placenta accreta ritention.

The term retained products of conception (RPOC) refers to intrauterine tissue that develops after conception and persists after medical and surgical pregnancy termination, miscarriage, and vaginal or cesarean delivery. One of the most important factor risk for RPOC is placenta accreta, defined as "the abnormal adherence, either in whole or in part, of the afterbirth to the underlying uterine wall". We report a case of a 37 years old woman referred to our gynecologic department with irregular vaginal bleeding. On her medical history, she had a cesarean occurred 3 months before. Ultrasonography revealed in the uterine cavity hyperechoic mass, treated with curettage. Two weeks later the curettage, patient complained still vaginal bleeding. On the transvaginal ultrasound, the uterine cavity was occupied again by a hyperechoic mass. She underwent to hysteroscopic resection and histological diagnosis was compatible with placenta accreta residual. In the follow up she had not complications. Early diagnosis, prompt evaluation of bleeding is important for timely treatment and for preventing immediate complications and demolitive approach. A careful follow up is necessary to prevent late consequences. The purpose of this study is to report our experience in timely diagnosis and conservative management.

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

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.