A retrospective study on IVF outcome in euthyroid patients with anti-thyroid antibodies: effects of levothyroxine, acetyl-salicylic acid and prednisolone adjuvant treatments

<p>Abstract</p> <p>Background</p> <p>Anti-thyroid antibodies (ATA), even if not associated with thyroid dysfunction, are suspected to cause poorer outcome of in vitro fertilization (IVF).</p> <p>Methods</p> <p>We retrospectively analyzed: (a) the prevalence of ATA in euthyroid infertile women, (b) IVF outcome in euthyroid, ATA+ patients, and (c) the effect of adjuvant treatments (levothyroxine alone or associated with acetylsalicylic acid and prednisolone) on IVF results in ATA+ patients. One hundred twenty-nine euthyroid, ATA+ women undergoing IVF were compared with 200 matched, ATA-controls. During IVF cycle, 38 ATA+ patients did not take any adjuvant treatment, 55 received levothyroxin (LT), and 38 received LT +acetylsalicylic acid (ASA)+prednisolone (P).</p> <p>Results</p> <p>The prevalence of ATA among euthyroid, infertile patients was 10.5%, similar to the one reported in euthyroid women between 18 and 45 years. ATA+ patients who did not receive any adjuvant treatment showed significantly poorer ovarian responsiveness to stimulation and IVF results than controls. ATA+ patients receiving LT responded better to ovarian stimulation, but had IVF results as poor as untreated ATA+ women. Patients receiving LT+ASA+P had significantly higher pregnancy and implantation rates than untreated ATA+ patients (PR/ET 25.6% and IR 17.7% vs. PR/ET 7.5% and IR 4.7%, respectively), and overall IVF results comparable to patients without ATA (PR/ET 32.8% and IR 19%).</p> <p>Conclusion</p> <p>These observations suggest that euthyroid ATA+ patients undergoing IVF could have better outcome if given LT+ASA+P as adjuvant treatment. This hypothesis must be verified in further randomized, prospective studies.</p

Expression of costimulatory molecules in the bovine corpus luteum

BACKGROUND: Bovine luteal parenchymal cells express class II major histocompatibility complex (MHC) molecules and stimulate class II MHC-dependent activation of T cells in vitro. The ability of a class II MHC-expressing cell type to elicit a response from T cells in vivo is also dependent on expression of costimulatory molecules by the antigen presenting cell and delivery of a costimulatory signal to the T cell. Whether bovine luteal parenchymal cells express costimulatory molecules and can deliver the costimulatory signal is currently unknown. METHODS: Bovine luteal tissue was collected during the early (day 5; day of estrus = day 0), mid (day 11–12), or late (day 18) luteal phase of the estrous cycle, and at 0, 0.5, 1, 4, 12 or 24 hours following administration of PGF2alpha to cows on day 10 of the estrous cycle. Northern analysis was used to measure CD80 or CD86 mRNA concentrations in luteal tissue samples. Mixed luteal parenchymal cell cultures and purified luteal endothelial cell cultures were prepared, and real-time RT-PCR was used to examine the presence of CD80 and CD86 mRNA in each culture type. Monoclonal antibodies to CD80 and CD86 were added to a mixed luteal parenchymal cell-T cell co-culture in vitro T cell proliferation assay to assess the functional significance of costimulatory molecules on activation of T lymphocytes by luteal parenchymal cells. RESULTS: Northern analysis revealed CD80 and CD86 mRNAs in luteal tissue, with greatest steady-state concentrations at midcycle. CD80 and CD86 mRNAs were detected in mixed luteal parenchymal cell cultures, but only slight amounts of CD80 (and not CD86) mRNA were detected in cultures of luteal endothelial cells. Luteinizing hormone, PGF2alpha and TNF-alpha were without effect on concentrations of CD80 or CD86 mRNA in mixed luteal parenchymal cells cultures. Anti-CD80 or anti-CD86 monoclonal antibodies inhibited T cell proliferation in the in vitro T cell proliferation assay. CONCLUSION: It can be concluded from this study that parenchymal cells within the bovine CL express functional costimulatory molecules that facilitate interactions between with T cells, and these components of the antigen presentation pathway are expressed maximally in the midcycle CL

Endocrine Disruptor Regulation of MicroRNA Expression in Breast Carcinoma Cells

Several environmental agents termed "endocrine disrupting compounds" or EDCs have been reported to bind and activate the estrogen receptor-α (ER). The EDCs DDT and BPA are ubiquitously present in the environment, and DDT and BPA levels in human blood and adipose tissue are detectable in most if not all women and men. ER-mediated biological responses can be regulated at numerous levels, including expression of coding RNAs (mRNAs) and more recently non-coding RNAs (ncRNAs). Of the ncRNAs, microRNAs have emerged as a target of estrogen signaling. Given the important implications of EDC-regulated ER function, we sought to define the effects of BPA and DDT on microRNA regulation and expression levels in estrogen-responsive human breast cancer cells.To investigate the cellular effects of DDT and BPA, we used the human MCF-7 breast cancer cell line, which is ER (+) and hormone sensitive. Our results show that DDT and BPA potentiate ER transcriptional activity, resulting in an increased expression of receptor target genes, including progesterone receptor, bcl-2, and trefoil factor 1. Interestingly, a differential increase in expression of Jun and Fas by BPA but not DDT or estrogen was observed. In addition to ER responsive mRNAs, we investigated the ability of DDT and BPA to alter the miRNA profiles in MCF-7 cells. While the EDCs and estrogen similarly altered the expression of multiple microRNAs in MCF-7 cells, including miR-21, differential patterns of microRNA expression were induced by DDT and BPA compared to estrogen.We have shown, for the first time, that BPA and DDT, two well known EDCs, alter the expression profiles of microRNA in MCF-7 breast cancer cells. A better understanding of the molecular mechanisms of these compounds could provide important insight into the role of EDCs in human disease, including breast cancer