Prostaglandin (PG) signaling has been implicated in embryonic implantation in several animal species including humans; however, this knowledge has not yet been clinically translated. The objective of this work is to investigate whether PGE 2 and PGF 2 ␣ in endometrial fluid (EF) can be used as biomarkers of human embryonic implantation. Patients and Methods: Lipidomic profile of human EF (n ϭ 173) obtained through natural cycles, hormonal replacement therapy, controlled ovarian stimulation, and

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... refractory endometrium induced by the insertion of an intrauterine device was analyzed by liquid chromatography and tandem mass spectrometry. Immunohistochemistry, Western blotting, immunolocalization of PG receptors on mouse embryos, embryo adhesion assay, pharmacological interventions, and statistical analysis were conducted. Results: PGE 2 and PGF 2 ␣ concentrations increased significantly in the human EF during the window of implantation in natural cycles and assisted reproductive technologies patients undergoing in vitro fertilization and ovum donation. This profile was abrogated in the refractory endometrium. We also demonstrated that PGE 2 and PGF 2 ␣ synthases are located in the endometrial epithelium being hormonally regulated during the window of implantation, and PG receptors are expressed in the trophoectoderm and inner cell mass of mouse blastocysts. Using an in vitro model of embryo adhesion, we demonstrated that inhibition of PGE 2 and PGF 2 ␣ or PG receptors (EP2 and FP) prevents embryo adhesion, which can be overcome by addingthesemoleculesbackorusingtheiragonists.Finally,inapilot study, we demonstrated that PGE 2 and PGF 2 ␣ levels from EF 24 hours prior to embryo transfer could predict pregnancy outcome. Conclusions: Our results suggest that PGE 2 and PGF 2 ␣ concentrations 24 hours prior to embryo transfer are potential noninvasive biomarkers of endometrial receptivity. Context: The mechanisms linking thyroid autoimmunity and iodine use in humans are unknown. Objective: To correlate iodine intake, thyroid autoimmunity, and recognition of thyroglobulin (Tg) epitopes after implementation of iodine prophylaxis. Setting: General community living in an Italian village. Main Outcome Measures: Thyroglobulin autoantibodies (TgAb), thyroperoxidase autoantibodies (TPOAb), and urinary iodine excretion were assessed in 906 iodized salt users (ISusers) and 389 nonusers (IS-nonusers). Ultrasound (US) was performed to identify thyroid hypoechogenicity, suggestive of Hashimoto thyroiditis (HT). TgAb epitope pattern in 16 IS-users and 17 IS-nonusers was evaluated by an inhibition binding assay to Tg, using human monoclonal TgAb-Fab directed to A, B, C, and D epitopes on Tg. Results: Median urinary iodine excretion was slightly higher in IS-users than in IS-nonusers (112.0 g/L vs 86.5 g/L; P Ͻ .01). TgAb, and not TPOAb, was more frequent in IS-users (18.9% vs 13.6%, P ϭ .02). HT-US was found in 87 subjects, among whom both positive TgAb (58.4% vs 31.8%, P ϭ .03) and TPOAb (61.5% vs 45.4%. P ϭ .04) were more frequent in IS-users. In this group significantly higher serum levels of TgAb (median 108 U/mL vs 30 U/mL; P ϭ .02), but not of TPOAb, were present. Iodized salt use had no effect on the 1208 non HT-US subjects. TgAb directed to the epitope B of Tg were more frequent in IS-users than in IS-nonusers (27.5% vs 3.0%, P ϭ .047). Conclusions: Iodine-induced thyroid autoimmunity is related to TgAb and the unmasking of a cryptic epitope on Tg contributes to this relationship in humans. Objective: Image-based localization of medullary thyroid cancer (MTC) and parathyroid glands would improve the surgical outcomes of these diseases. MTC and parathyroid glands express high levels of calcium-sensing receptor (CaSR). The aim of this study was to prove the concept that CaSR antagonists specifically localize to CaSR-expressing tumors in vivo. Design: We synthesized two isomers of a known CaSR calcilytic, Calhex 231, and four new analogues, which have a favorable structure for labeling. Their antagonistic activity was determined using immunoblots demonstrating decreased Context: Masculinization depends on the fetal testis. Exposure of the human fetus during pregnancy to paracetamol and/or to other mild analgesics is associated with an increased risk of cryptorchidism. Objective: We aimed to determine whether mild analgesics disruptedthemorphologyandendocrinefunctionofthehumantestis. Design: We used an in vitro system based on the culture of human fetal testes exposed or not to paracetamol, its metabolite N-(4-hydroxyphenyl)-arachidonoylethanolamide (AM404), aspirin, indomethacin, and ketoconazole at 10 Ϫ4 to 10