Thyroid peroxidase in human endometrium and placenta: a potential target for anti-TPO antibodies.

Autoimmune thyroid disease is the most common endocrine disorder during pregnancy. Thyroid autoantibodies (TAs) have been suggested to serve a role in implantation failure and spontaneous abortion. Until now, there are no data on the potential interaction of TAs with human reproductive organs. Here, we set out for the first time to test this hypothesis by studying the expression of thyroid peroxidase (TPO) at gene and protein level in human reproductive organs. Endometrial samples were taken from normal women, and placenta tissues were collected after full-term caesarian section. Expression of TPO messenger RNA (mRNA) was investigated by qRT-PCR. In addition, polyclonal anti-TPO antibodies were produced and the expression of TPO protein in mentioned tissues was evaluated by immunohistochemistry and Western blot analysis. The reactivity of anti-TPO antibody in human embryos was evaluated by immunofluorescent staining. For the first time, our study showed that TPO is expressed at gene and protein levels in endometrium and placenta. TPO expression was mainly localized to glandular and luminal epithelial cells in the endometrium. In placenta, the syncytiotrophoblasts and invasive trophoblast cells were the main cell types that expressed TPO protein. Specific band of approximately 110 kDa was observed in all endometrial and placental tissues by Western blot analysis. However, no expression of TPO protein was observed in human embryo. TPO expression in endometrium and placenta may explain higher frequency of abortion and infertility in patients with thyroid autoimmunity.

Cross-talk between oxidative stress signaling and microRNA regulatory systems in carcinogenesis: Focused on gastrointestinal cancers.

Molecular mechanisms underlying development and progression of gastrointestinal (GI) cancers are mediated by both oxidative stress (OS) and microRNAs (miRNAs) involvement. Notably, OS signaling may regulate the expression of miRNAs, and miRNAs function as imperative players in OS-initiated tumors. Given the defined biological roles of both OS systems and miRNAs in GI carcinogenesis, a possible interplay between these two key cellular networks is considered. A growing body of evidence has indicated a reciprocal connection between OS signaling pathways and miRNA regulatory machines in GI cancer development and progression. Illumination of the molecular cross-talking between miRNAs and the OS would improve our pathophysiological insight into carcinogens. Also, understanding the molecular mechanisms in which these systems are reciprocally regulated may imply in future medical practice mainly GI cancer therapy. Nowadays, therapeutic strategies focusing on miRNA and OS in GI cancer treatment are increasingly delineated. Since the use of antioxidants is limited owing to the contrasting consequences of OS signaling in cancer, the discovery of OS-responsive miRNAs may provide a potential new strategy to overcome OS-mediated GI carcinogenesis. Given the possible interaction between OS and miRNAs in GI cancers, this review aimed to elucidate the existing evidence on the interaction between OS and miRNA regulatory machinery and its role in GI carcinogenesis. In this regard, we will illustrate the function of miRNAs which target OS systems during homeostasis and tumorigenesis. We also discuss the biological cross-talk between OS systems and miRNAs and corresponding cell signaling pathways.

Gene expression analysis of membrane progesterone receptors in women with recurrent spontaneous abortion: a case control study.

OBJECTIVE: Recurrent spontaneous abortion (RSA) is a condition which is defined as three consecutive pregnancy losses prior to 20 weeks from the last menstrual period. Progesterone is a steroid hormone that has an essential role in the implantation and maintenance of pregnancy. The progesterone signaling is performed by nuclear progesterone receptors (NPRs) and membrane progesterone receptors (mPR). The aim of this study was to analyze gene expression of mPR-α, mPR-ß and NPR in the endometrium of patients with a history of RSA compared to normal fertile women. RESULTS: In this study, endometrial samples were obtained from 10 women with a history of RSA and 10 fertile women during days 10-14 of menstrual cycle. Relative expression of mPR-α, mPR-ß and NPR genes were studied by a quantitative real time polymerase chain reaction (qRT-PCR) and compared between the two groups. The mean relative expression of mPR-ß gene was significantly lower in the case group compared to the fertile women (p < 0.05). However, the gene expression of mPR-α and NPR showed no significant difference between two groups. The findings suggest a reduction of endometrial gene expression of mPR-ß in RSA patients may play an important role in pathogenesis of RSA.