The investigation of hippo signaling pathway in mouse uterus during peri-implantation period.

PURPOSE: Events in the uterus during the peri-implantation period include embryo development, acquisition of uterine receptivity, implantation and decidualization. Hippo signaling pathway regulates cell proliferation, apoptosis and differentiation. We aimed to determine localization and expressions of pYAP (Phospho Yes-associated protein), YAP (Yes-associated protein), TEAD1 (TEA domain family member 1) and CTGF (Connective tissue growth factor), members of the Hippo signaling pathway, in the mouse uterus during the peri-implantation period. METHODS: Pregnant mice were randomly separated into 5 groups: 1st, 4th, 5th, 6th, and 8th days of pregnancy groups. Non-pregnant female mice in estrous phase were included in the estrous group. Uteri and implantation sites were collected. Also, inter-implantation sites were collected from the 5th day of pregnancy group. pYAP, YAP, TEAD-1 and CTGF were detected by immunohistochemistry and Western blotting. RESULTS: We observed that the expressions of YAP, TEAD-1 and CTGF were increased in the luminal and glandular epithelium on the 1st and 4th days of pregnancy when epithelial proliferation occurred. pYAP expression was high, and YAP and CTGF expressions were low in the luminal epithelium of the implantation sites on the 5th day of pregnancy, when epithelial differentiation occurred. pYAP expression was low, YAP and CTGF expressions were high at implantation sites on the 6th and 8th days of pregnancy, where decidua was formed. CONCLUSION: Our findings suggest that the Hippo signaling pathway might be involved in implantation and decidualization. Our findings will guide further studies and may help to elucidate underlying causes of implantation failure and pregnancy loss.

NLRP3 inflammasome pathway, the hidden balance in pregnancy: A comprehensive review.

The balance of the inflammatory response is indispensable during pregnancy. Inflammasomes are the cytosolic supramolecular protein complexes activated by pattern recognition receptors. These receptors recognize the pathogen and damage/danger-associated molecular patterns. NLRP3 inflammasome complex consists mainly of NLRP3 (leucine-rich repeat-containing and pyrin domain-containing protein 3), a cytosolic sensor molecule, ASC (apoptosis-associated speck-like protein containing a CARD) protein and a cysteine protease pro-caspase-1 as an effector molecule. This complex has a role in producing inflammatory cytokines, interleukin 1 beta and interleukin 18, and inflammasome-dependent programmed cell death pathway pyroptosis. In this review, we focused on and summarised the NLRP3 inflammasome and its roles in normal and pathological pregnancies. The NLRP3 inflammasome pathway influences endometrial receptivity and embryo invasion by inducing epithelial-mesenchymal transition. Abnormal inflammasome activation in the endometrium may adversely affect endometrial receptivity. In addition, NLRP3 inflammasome pathway overactivation may mediate the abnormal inflammatory response at the maternal-fetal interface and be associated with pregnancy complications, such as recurrent implantation failure, pregnancy loss, pre-term birth and pre-eclampsia. Therefore, targeting the NLRP3 inflammasome pathway could develop a new therapeutic approach to prevent the aforementioned pregnancy pathologies.

The investigation of apelin and apelin receptor expressions in mouse endometrium during peri-implantation period.

BACKGROUND: Fertilization, pre-implantation embryo development, implantation, and decidualization are critical for a healthy pregnancy. Successful implantation requires a competent blastocyst and a receptive uterus. Apelin was purified from the bovine stomach in 1998. Apelin receptor (APJ) is a member of G protein-coupled receptors. Apelin/APJ system's physiological role was shown in cardiovascular system, immune response, stress response, fluid regulation, nutrient uptake, angiogenesis, and adipoinsular axis; however, whether apelin/APJ system plays a role in implantation is unknown. In our study, we aimed to evaluate the localization and expressions of the apelin/APJ system in the peri-implantation period mouse uterus. METHODS: Uteri and implantation sites were collected from mice on the estrous phase and the 1st, 4th, 5th, 6th, and 8th days of pregnancy. Also, inter-implantation sites were collected from the 5th day of the pregnancy group. Localization and expressions of apelin and APJ were determined by immunohistochemistry and Western blot, respectively. RESULTS: Apelin and APJ were expressed in the luminal and gland epithelium, the stroma of all experimental groups. Two isoforms of apelin-8 and 16 kDa were detected by Western blot. While apelin expression increased from the estrous to the 8th day of pregnancy, APJ expression increased from the estrous to the 4th day of pregnancy, reached the highest expression level, then decreased. CONCLUSIONS: Our findings suggest that the apelin/APJ system might be involved in implantation and decidualization. Our findings will guide further studies and may help elucidate the underlying causes of implantation failure and pregnancy loss.

Carvacrol treatment opens Kir6.2 ATP-dependent potassium channels and prevents apoptosis on rat testis following ischemia-reperfusion injury model.

Testicular torsion is a urological problem that causes subfertility and testicular damage in males. Testis torsion and detorsion lead to ischemia-reperfusion (IR) injury in the testis. Testicular IR injury causes the increase of reactive oxygen species (ROS), oxidative stress (OS) and germ cell-specific apoptosis. In this study, we aimed to investigate whether Carvacrol has a protective effect on testicular IR injury and its effects on Kir6.2 channels, which is a member of adenosine triphosphate (ATP)-dependent potassium channels. In the study, 2-4 months old 36 albino Wistar rats were used. For experimental testicular IR model, the left testis was rotated counterclockwise at 720° for two hours, and after two hours following torsion, detorsion was performed. Carvacrol was dissolved in 5% Dimethyl Sulfoxide (DMSO) at a dose of 73 mg∕kg and half an hour before detorsion, 0.2 mL was administered intraperitoneally. In testicular tissues, caspase 3 and Kir6.2 immunoexpressions were examined. Serum malondialdehyde (MDA) and testosterone levels were measured. Apoptotic cells and serum MDA levels were significantly decreased and Kir6.2 activation was significantly increased in Carvacrol-administrated IR group. As a result of our study, Carvacrol may activates Kir6.2 channels and inhibits apoptosis and may have a protective effect on testicular IR injury.

Cervical sympathectomy modulates the neurogenic inflammatory neuropeptides following experimental subarachnoid hemorrhage in rats.

BACKGROUND: Neuroinflammation is implicated in cerebral vasospasm and brain injuries after subarachnoid hemorrhage (SAH). In addition to classical neuroinflammation with increased inflammatory cytokines, a sterile neurogenic inflammation characterized by release of potent vasoactive neuropeptides may be responsible for brain injuries after SAH. Sympathetic discharges from superior cervical ganglion contribute to vasoconstriction of cerebral arteries Thus, we investigated the effects of surgical cervical sympathectomy on the neurogenic inflammatory neuropeptides shortly after SAH induction in a model of SAH in rats. METHODS: Male Wistar rats were divided into 4 groups: control; was not touched, saline group; 300 µl of saline was injected into prechiasmatic cistern, SAH+Sham group; 300 µl of autologous blood was injected to induce subarachnoid hemorrhage into prechiasmatic cistern; SAH+Symp group; the left cervical sympathetic branch was surgically removed after the induction of SAH. Levels of neuropeptides CGRP, SP and VIP which are responsible for neurogenic inflammation, in plasma, trigeminal ganglion, brainstem and brain tissue were measured by ELISA. In addition, c-fos expression as a marker of neuronal activation in the trigeminal nucleus caudalis (TNC) was determined by immunohistochemical staining. RESULTS: SAH significantly increased c-fos expression in the TNC, as well as CGRP, SP and VIP concentrations in plasma and trigeminal ganglion neurons, and also CGRP and SP concentrations in the brainstem. Cervical sympathectomy application significantly reduced the increases in these parameters induced by SAH. CONCLUSIONS: Our findings suggest that cervical sympathectomy treatment may prevent early brain injury by modulating SAH-induced neurogenic inflammatory neuropeptides such as CGRP, SP and VIP, and improve the quality of life in survivors following SAH.