Actin crosslinking protein filamin A during early pregnancy in the rat uterus

2016 ◽  
Vol 28 (7) ◽  
pp. 960 ◽  
Author(s):  
Romanthi J. Madawala ◽  
Connie E. Poon ◽  
Samson N. Dowland ◽  
Christopher R. Murphy

During early pregnancy the endometrium undergoes a major transformation in order for it to become receptive to blastocyst implantation. The actin cytoskeleton and plasma membrane of luminal uterine epithelial cells (UECs) and the underlying stromal cells undergo dramatic remodelling to facilitate these changes. Filamin A (FLNA), a protein that crosslinks actin filaments and also mediates the anchorage of membrane proteins to the actin cytoskeleton, was investigated in the rat uterus at fertilisation (Day 1) and implantation (Day 6) to determine the role of FLNA in actin cytoskeletal remodelling of UECs and decidua during early pregnancy. Localisation of FLNA in UECs at the time of fertilisation was cytoplasmic, whilst at implantation it was distributed apically; its localisation is under the influence of progesterone. FLNA was also concentrated to the first two to three stromal cell layers at the time of fertilisation and shifted to the primary decidualisation zone at the time of implantation. This shift in localisation was found to be dependent on the decidualisation reaction. Protein abundance of the FLNA 280-kDa monomer and calpain-cleaved fragment (240 kDa) did not change during early pregnancy in UECs. Since major actin cytoskeletal remodelling occurs during early pregnancy in UECs and in decidual cells, the changing localisation of FLNA suggests that it may be an important regulator of cytoskeletal remodelling of these cells to allow uterine receptivity and decidualisation necessary for implantation in the rat.

Reproduction ◽  
2004 ◽  
Vol 128 (2) ◽  
pp. 197-205 ◽  
Author(s):  
Chun-Bo Teng ◽  
Hong-Lu Diao ◽  
Hong Ma ◽  
Jing Cong ◽  
Hao Yu ◽  
...  

Signal transducer and activator of transcription 3 (Stat3), a member of the Stat family, is specifically activated during mouse embryo implantation. The aim of this study was to investigate the expression, activation and regulation of Stat3 in rat uterus during early pregnancy, pseudopregnancy, delayed implantation and artificial decidualization. Stat3 mRNA was highly expressed in the luminal epithelium on day 5 and in the luminal epithelium and underlying stromal cells at implantation sites on day 6 of pregnancy. There was a strong level of Stat3 protein expression and phosphorylation in the stromal cells near the lumen and in the luminal epithelium on day 5 of pregnancy, which was similar to day 5 of pseudopregnancy. In the afternoon of day 6, the strong level of Stat3 phosphorylation was detected only in the luminal epithelium. Stat3 was highly expressed and activated in the decidual cells from days 7 to 9 of pregnancy and under artificial decidualization in the present study. Our results suggest that the strong level of Stat3 activation in the luminal epithelium and underlying stromal cells during the pre-implantation period may be important for establishing uterine receptivity as in mice, and the high level of Stat3 expression and activation in decidual cells may play a role during decidualization.


Reproduction ◽  
2006 ◽  
Vol 131 (2) ◽  
pp. 369-378 ◽  
Author(s):  
Laura A Lindsay ◽  
Christopher R Murphy

During early pregnancy in the rat there is a dramatic reduction in luminal fluid which is associated with uterine receptivity for blastocyst implantation. This study investigates the presence and distributional changes of several members of the aquaporin (AQP) family in the rat uterus in response to hormonal regime. An increase in apical AQP5 protein expression was found in response to progesterone alone or in combination with oestrogen, which is similar to that seen at the time of implantation. AQP1 was found in endothelial cells of the endometrium and in the inner circular layer of smooth muscle, with maximal protein expression seen after three doses of progesterone plus 8 hr of oestrogen treatment. These results, for the first time, show that the up-regulation of AQP5 in the apical plasma membrane of uterine epithelial cells and AQP1 in the inner circular layer of myometrium, is dependent on progesterone. Furthermore, unlike during normal pregnancy, there is no differential gradient of AQP5 expression between mesometrial and antimesometrial poles of the progesterone treated uterus. Hence it is suggested that the differential gradient of AQP5 is dependent on the presence of a blastocyst, in addition to the appropriate hormonal environment.


Reproduction ◽  
2017 ◽  
Vol 154 (5) ◽  
pp. 595-605 ◽  
Author(s):  
Seo-Ho Lee ◽  
Byung-Ju Kim ◽  
Uh-Hyun Kim

CD31 has been shown to play a role in endothelial cell migration and angiogenesis, which are critical to the formation and function of the endometrium and myometrium in uterine development during early pregnancy. However, the role of CD31 in uterine receptivity during blastocyst implantation is poorly understood. The pregnancy rate in CD31−/− female mice mated with CD31+/+ male mice was higher than that observed in CD31+/+ female mice mated with CD31+/+ male mice. During the receptive phase of implantation, uterine glands were more developed in CD31−/− mice than in CD31+/+ mice, and the uterine weights of CD31−/− mice were increased. Leukemia inhibitory factor (LIF) was highly expressed in the CD31−/− mice during implantation and the expression of LIF was up-regulated by estradiol-17β (E2) + progesterone (P4) in ovariectomized CD31−/− mice, compared with CD31+/+ mice at 8 h after hormone treatment. E2-induced protein synthesis was inhibited by P4 in the CD31+/+ uterus, but not in the uterus of CD31−/− mice. Also, STAT3, HAND2, LIF, and mTOR signals were enhanced in CD31−/− mice. Stromal DNA replication was highly activated in the uterus of CD31−/− mice, manifested by upregulated cyclin series signaling and PCNA expression after E2 + P4treatment. Collectively, CD31 inhibits E2-mediated epithelial proliferation via recruitment and phosphorylation of SHP-2 upon receiving P4signal in early pregnancy.


2021 ◽  
Vol 22 (15) ◽  
pp. 7932
Author(s):  
Sourav Panja ◽  
John T. Benjamin ◽  
Bibhash C. Paria

Maternal infection-induced early pregnancy complications arise from perturbation of the immune environment at the uterine early blastocyst implantation site (EBIS), yet the underlying mechanisms remain unclear. Here, we demonstrated in a mouse model that the progression of normal pregnancy from days 4 to 6 induced steady migration of leukocytes away from the uterine decidual stromal zone (DSZ) that surrounds the implanted blastocyst. Uterine macrophages were found to be CD206+ M2-polarized. While monocytes were nearly absent in the DSZ, DSZ cells were found to express monocyte marker protein Ly6C. Systemic endotoxic lipopolysaccharide (LPS) exposure on day 5 of pregnancy led to: (1) rapid (at 2 h) induction of neutrophil chemoattractants that promoted huge neutrophil infiltrations at the EBISs by 24 h; (2) rapid (at 2 h) elevation of mRNA levels of MyD88, but not Trif, modulated cytokines at the EBISs; and (3) dose-dependent EBIS defects by day 7 of pregnancy. Yet, elimination of maternal neutrophils using anti-Ly6G antibody prior to LPS exposure failed to avert LPS-induced EBIS defects allowing us to suggest that activation of Tlr4-MyD88 dependent inflammatory pathway is involved in LPS-induced defects at EBISs. Thus, blocking the activation of the Tlr4-MyD88 signaling pathway may be an interesting approach to prevent infection-induced pathology at EBISs.


1994 ◽  
Vol 266 (3) ◽  
pp. F367-F374 ◽  
Author(s):  
R. Rick

The pH of the isolated frog skin epithelium was determined on a cellular and subcellular level based on the distribution of a weak organic acid, 4-bromobenzoic acid. The indicator is detectable by X-ray microanalysis due to the presence of an element label. The results show that the pH of principal cells, but not the Na concentration, is closely correlated with the rate of transepithelial Na transport. Acidification leads to an inhibition of Na transport, regardless of whether the change was spontaneous or experimentally induced. Under the conditions of this study, the pH of principal cells was not well regulated. At a bath pH of 7.0, large pH differences between the cell layers were detectable. In mitochondria-rich cells, the pH was a function of the intracellular Cl concentration but not the Na transport rate. The cytoplasmic pH consistently exceeded the nuclear pH. The nuclear-cytoplasmic pH differential in principal cells amounted to 0.3 pH units, which is equivalent to a nuclear potential of -17 mV. The results support the view that the intracellular pH (pHi) is an important regulator of transepithelial Na transport. Regulation is primarily achieved at the level of the apical Na channel, making the Na influx the rate-limiting step in Na reabsorption.


Endocrinology ◽  
2019 ◽  
Vol 161 (1) ◽  
Author(s):  
Arin K Oestreich ◽  
Sangappa B Chadchan ◽  
Pooja Popli ◽  
Alexandra Medvedeva ◽  
Marina N Rowen ◽  
...  

Abstract Uterine receptivity is critical for establishing and maintaining pregnancy. For the endometrium to become receptive, stromal cells must differentiate into decidual cells capable of secreting factors necessary for embryo survival and placental development. Although there are multiple reports of autophagy induction correlated with endometrial stromal cell (ESC) decidualization, the role of autophagy in decidualization has remained elusive. To determine the role of autophagy in decidualization, we utilized 2 genetic models carrying mutations to the autophagy gene Atg16L1. Although the hypomorphic Atg16L1 mouse was fertile and displayed proper decidualization, conditional knockout in the reproductive tract of female mice reduced fertility by decreasing the implantation rate. In the absence of Atg16L1, ESCs failed to properly decidualize and fewer blastocysts were able to implant. Additionally, small interfering RNA knock down of Atg16L1 was detrimental to the decidualization response of human ESCs. We conclude that Atg16L1 is necessary for decidualization, implantation, and overall fertility in mice. Furthermore, considering its requirement for human endometrial decidualization, these data suggest Atg16L1 may be a potential mediator of implantation success in women.


1999 ◽  
Vol 14 (Suppl_3) ◽  
pp. 269-269
Author(s):  
A. Lanzone ◽  
E. Pierro ◽  
F. Minici ◽  
C.L. Andreani ◽  
F. Miceli ◽  
...  

2021 ◽  
Author(s):  
Yan Zhang ◽  
Linchao Zhang ◽  
JiaLu Bao ◽  
LianTao Liu ◽  
Xiaodan Wang

Abstract To investigate the mechanism perfluorooctanoic acid (PFOA)’s toxicity on the uterus and liver of the mice during early pregnancy, pregnant mice were given 0, 1, 5, 10, 20, 40 mg/kg PFOA daily by gavage from gestational day (GD) 1-7, and sacrificed on GD 9. Uterus and liver weight were recorded, liver and uterine indexes were calculated, histopathological changes of the liver and uterus were examined, and levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) in liver were detected by spectrophotometric method. Expression of FAS, FASL, Bax, Bcl-2, and Caspase-3 in decidual cells were detected by immunohistochemistry and the TUNEL method was used to detect apoptotic uterine cells. Results showed that liver weight increased, and the uterus index was significantly reduced at 40 mg/kg compared with the control group. With increasing doses of PFOA, levels of SOD and GSH-PX were significantly decreased, and MDA significantly increased in liver tissue. 20 mg/kg and 40 mg/kg of PFOA caused greater harm to the uterus and congestion and resorption may occur. Expression of FAS, FASL, Bax, and Caspase-3 in decidual cells of the uterus in PFOA treatment groups significantly increased in a dose-dependent manner. The expression of Bcl-2 was down-regulated, which decreased the ratio of Bcl-2/Bax. It is therefore proposed that oxidative damage may be one of the mechanisms by which PFOA induces liver toxicity, and a subsequent increase in uterine cell apoptosis may induce embryo loss or damage.


Nanoscale ◽  
2019 ◽  
Vol 11 (25) ◽  
pp. 12285-12295 ◽  
Author(s):  
Magdalena Karolczak-Bayatti ◽  
Karen Forbes ◽  
James Horn ◽  
Tambet Teesalu ◽  
Lynda K. Harris ◽  
...  

A complex combination of trafficking and signaling occurs at the surface of the placenta. We explain how signals from maternal growth factors may be transmitted to deeper cell layers.


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