In the next experiments using a
In the next experiments, using a Cell Stress Array kit we assessed the effect of mixture of progestogens on the expression of 26 proteins. One group of proteins including PON3, Phospho-p38a, SIRT2, SOD2, HIF-1 alpha, HIF-2alpha and p27 were upregulated upon progestogen treatment. HIF-1 functions as a master regulator of cellular and systemic homeostatic response to hypoxia by activating transcription of many genes, including those involved in energy metabolism, apoptosis, and other genes whose products increase oxygen delivery or facilitate metabolic adaptation (Iyer et al., 1998, Oldham et al., 2015, Semenza, 2010, Wang et al., 1995). The PON3 encoded protein is secreted into the bloodstream and associates with HDL. The protein also rapidly hydrolyzes lactones and can inhibit the oxidation of LDL. The observation was in accordance with the lowered level of LDL measured from the serum (Shamir et al., 2005). Phospho-p38a is the mitogen-activated protein kinase 14, the protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various environmental stresses and pro-inflammatory cytokines (Eckert et al., 2003, Grossi et al., 2014). SIRT2-like family deacetylases are involved in the normal ageing process through their role in resistance to cellular stress (Maxwell et al., 2011).
The NFҠB1 and FABP-1 were downregulated, NFҠB1 is a rapidly acting primary transcription factor found in all cell types. It is involved in cellular responses to stimuli such as cytokines and stress, and plays a key role in regulating the immune response to infection (Baeuerle, 1991). The roles of FABP-1 include fatty Cy5 EGFP uptake, transport, and metabolism. It is binding cholesterol and enhances in vitro cholesterol transfer between the plasma membrane and microsomes to stimulate cholesterol esterification by acyl-CoA cholesterol acyltransferase in vitro. FABP1 levels may act as a circulating biomarker of adiposity and insulin resistance related metabolic diseases (Huang et al., 2015). Triglyceride was independently associated with serum FABP1 (Peng et al., 2015). Additionally, hypertriglyceridemia and low HDL-cholesterol were significantly correlated to serum FABP1 levels (Shi et al., 2012). It increases the fatty acid transport, lipogenensis and lipid transport.
There were no changes in the protein levels of the HSP superfamily. Our results obtained during chronic progestogen treatment are in accordance with those published earlier. It was suggested that the HSPs adapt to the external environmental factors and although their levels increase during an acute treatment, chronic exposure restores them to the normal interval (Pechenino and Frick, 2009, Xie et al., 2014).
Our results show that mixture of progestogens cause significant morphological and molecular changes in this model organism, despite the relatively short exposure time (42 days) and the fact that the concentration of the progestogens in one of the treatment groups (10ng/L) was relevant concentration range in the worldwide watercourses and water body.
Preterm prelabor rupture of membranes (PROM), defined as <37 weeks gestational age, occurs in approximately 3% of pregnancies and contributes to 40% of preterm births. Neonatal outcomes may be improved with expectant management in the absence of infection to facilitate delivery at a later gestational age. Yet, many women with preterm PROM often deliver within 1 week. Antibiotics safely extend latency and decrease the risks of maternal and neonatal infection after preterm PROM., , Progestogen administration has been studied in different populations, , , , , and has been shown to prolong a pregnancy in specific populations that are at risk of prematurity, including women with a previous spontaneous preterm birth, and those with a short cervical length., These therapies generally are initiated in the second trimester when risk of preterm birth is identified by history or on ultrasound examination.