Deficiency of PARP-1 and PARP-2 in the mouse uterus results in decidualization failure and pregnancy loss

2021 ◽  
Vol 118 (40) ◽  
pp. e2109252118
Author(s):  
Andrew M. Kelleher ◽  
Rohit Setlem ◽  
Françoise Dantzer ◽  
Francesco J. DeMayo ◽  
John P. Lydon ◽  
...  
Keyword(s):  
Pregnancy Loss ◽  
Histological Analysis ◽  
Successful Pregnancy ◽  
Mouse Uterus ◽  
Genetic Ablation ◽  
P53 Signaling ◽  
Physiological Processes ◽  
Decidual Cells ◽  
Underlying Mechanisms ◽  
Parp 1

Miscarriage is a common complication of pregnancy for which there are few clinical interventions. Deficiency in endometrial stromal cell decidualization is considered a major contributing factor to pregnancy loss; however, our understanding of the underlying mechanisms of decidual deficiency are incomplete. ADP ribosylation by PARP-1 and PARP-2 has been linked to physiological processes essential to successful pregnancy outcomes. Here, we report that the catalytic inhibition or genetic ablation of PARP-1 and PARP-2 in the uterus lead to pregnancy loss in mice. Notably, the absence of PARP-1 and PARP-2 resulted in increased p53 signaling and an increased population of senescent decidual cells. Molecular and histological analysis revealed that embryo attachment and the removal of the luminal epithelium are not altered in uterine Parp1, Parp2 knockout mice, but subsequent decidualization failure results in pregnancy loss. These findings provide evidence for a previously unknown function of PARP-1 and PARP-2 in mediating decidualization for successful pregnancy establishment.

scholarly journals GPER-Deficient Rats Exhibit Lower Serum Corticosterone Level and Increased Anxiety-Like Behavior

2020 ◽  
Vol 2020 ◽  
pp. 1-22 ◽  
Author(s):  
Yi Zheng ◽  
Meimei Wu ◽  
Ting Gao ◽  
Li Meng ◽  
Xiaowei Ding ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Corticosterone Level ◽  
Brain Structures ◽  
Ample Evidence ◽  
Genetic Ablation ◽  
Serum Corticosterone ◽  
Underlying Mechanisms ◽  
G Protein Coupled ◽  
Prolonged Stress

Ample evidence suggests that estrogens have strong influences on the occurrence of stress-related mood disorders, but the underlying mechanisms remain poorly understood. Through multiple approaches, we demonstrate that the G protein-coupled estrogen receptor (GPER) is widely distributed along the HPA axis and in brain structures critically involved in mood control. Genetic ablation of GPER in the rat resulted in significantly lower basal serum corticosterone level but enhanced ACTH release in response to acute restraint stress, especially in the female. GPER-/- rats of either sex displayed increased anxiety-like behaviors and deficits in learning and memory. Additionally, GPER deficiency led to aggravation of anxiety-like behaviors following single-prolonged stress (SPS). SPS caused significant decreases in serum corticosterone in WT but not in GPER-deficient rats. The results highlight an important role of GPER at multiple sites in regulation of the HPA axis and mood.

scholarly journals Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology?

2014 ◽  
Vol 94 (4) ◽  
pp. 1027-1076 ◽  
Author(s):  
M. A. Hanson ◽  
P. D. Gluckman
Keyword(s):  
Animal Studies ◽  
Developmental Plasticity ◽  
Current Knowledge ◽  
Evolutionary Developmental Biology ◽  
Noncommunicable Disease ◽  
Normal Range ◽  
Physiological Processes ◽  
New Concepts ◽  
Health And Disease ◽  
Underlying Mechanisms

Extensive experimental animal studies and epidemiological observations have shown that environmental influences during early development affect the risk of later pathophysiological processes associated with chronic, especially noncommunicable, disease (NCD). This field is recognized as the developmental origins of health and disease (DOHaD). We discuss the extent to which DOHaD represents the result of the physiological processes of developmental plasticity, which may have potential adverse consequences in terms of NCD risk later, or whether it is the manifestation of pathophysiological processes acting in early life but only becoming apparent as disease later. We argue that the evidence suggests the former, through the operation of conditioning processes induced across the normal range of developmental environments, and we summarize current knowledge of the physiological processes involved. The adaptive pathway to later risk accords with current concepts in evolutionary developmental biology, especially those concerning parental effects. Outside the normal range, effects on development can result in nonadaptive processes, and we review their underlying mechanisms and consequences. New concepts concerning the underlying epigenetic and other mechanisms involved in both disruptive and nondisruptive pathways to disease are reviewed, including the evidence for transgenerational passage of risk from both maternal and paternal lines. These concepts have wider implications for understanding the causes and possible prevention of NCDs such as type 2 diabetes and cardiovascular disease, for broader social policy and for the increasing attention paid in public health to the lifecourse approach to NCD prevention.

scholarly journals Differential expression and regulation of Tdo2 during mouse decidualization

2013 ◽  
Vol 220 (1) ◽  
pp. 73-83 ◽  
Author(s):  
Dang-Dang Li ◽  
Ying-Jie Gao ◽  
Xue-Chao Tian ◽  
Zhan-Qing Yang ◽  
Hang Cao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Differential Expression ◽  
Stromal Cells ◽  
Real Time Pcr ◽  
Mouse Uterus ◽  
Decidual Cells ◽  
High Level ◽  
Rate Limiting

Tryptophan 2,3-dioxygenase (Tdo2) is a rate-limiting enzyme which directs the conversion of tryptophan to kynurenine. The aim of this study was to examine the expression and regulation of Tdo2 in mouse uterus during decidualization. Tdo2 mRNA was mainly expressed in the decidua on days 6–8 of pregnancy. By real-time PCR, a high level of Tdo2 expression was observed in the uteri from days 6 to 8 of pregnancy, although Tdo2 expression was observed on days 1–8. Simultaneously, Tdo2 mRNA was also detected under in vivo and in vitro artificial decidualization. Estrogen, progesterone, and 8-bromoadenosine-cAMP could induce the expression of Tdo2 in the ovariectomized mouse uterus and uterine stromal cells. Tdo2 could regulate cell proliferation and stimulate the expression of decidual marker Dtprp in the uterine stromal cells and decidual cells. Overexpression of Tdo2 could upregulate the expression of Ahr, Cox2, and Vegf genes in uterine stromal cells, while Tdo2 inhibitor 680C91 could downregulate the expression of Cox2 and Vegf genes in uterine decidual cells. These data indicate that Tdo2 may play an important role during mouse decidualization and be regulated by estrogen, progesterone, and cAMP.

scholarly journals Biomass accumulation and physiological responses of tomato plants to magnetically–treated water in hydroponic conditions

2021 ◽  
Author(s):  
Daniel I. Ospina-Salazar ◽  
Shimon Rachmilevitch ◽  
Santiago Cuervo-Jurado ◽  
Orlando Zúñiga-Escobar
Keyword(s):  
Stomatal Conductance ◽  
Water Potential ◽  
Biomass Accumulation ◽  
Lower Surface ◽  
Tomato Plants ◽  
Treated Water ◽  
Fresh Biomass ◽  
Physiological Processes ◽  
Underlying Mechanisms ◽  
Hydroponic Conditions

AbstractMagnetically-treated water (MTW) has been reported to enhance biomass accumulation in plants. However, the underlying mechanisms are not fully understood, and the existing reports only deal with soil-grown plants. Thus, the purpose of this experiment was to assess whether or not MTW affects main physiological processes (gas exchange, biomass accumulation and water potential) in tomato plants whose water supply was only MTW. Two experiments were done in hydroponic semi-controlled conditions, consisting of a loop system with permanent recirculation of water through a non-uniform magnet. The plants grown under MTW showed a significant increase in chlorophyll content, photosynthesis and transpiration at high light irradiances, although the increase in stomatal conductance was less significant. MTW also increased fruit fresh biomass, number of fruits and root dry biomass in 61.7 %, 85.3 % and 30.3 % respectively, but this was only achieved at natural sunlight conditions. Moreover, treated plants showed higher root hydraulic conductance and leaf water potential, which is thought to be related with a lower surface tension of MTW, an effect that is consistent with previous studies. The higher biomass accumulation in tomato plants under MTW is likely explained because of a faster water transport from the roots to the leaves via xylem, which in turn increases H2O efflux and CO2 assimilation in the leaves, thanks to a higher stomatal conductance.

scholarly journals Dual functions of Rack1 in regulating Hedgehog pathway

2020 ◽  
Vol 27 (11) ◽  
pp. 3082-3096 ◽  
Author(s):  
Yan Li ◽  
Xiaohan Sun ◽  
Dongqing Gao ◽  
Yan Ding ◽  
Jinxiao Liu ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Cellular Localization ◽  
Multiple Roles ◽  
Dual Roles ◽  
Cubitus Interruptus ◽  
Trimeric Complex ◽  
Physiological Processes ◽  
Underlying Mechanisms ◽  
The Stability ◽  
Fine Tune

Abstract Hedgehog (Hh) pathway plays multiple roles in many physiological processes and its dysregulation leads to congenital disorders and cancers. Hh regulates the cellular localization of Smoothened (Smo) and the stability of Cubitus interruptus (Ci) to fine-tune the signal outputs. However, the underlying mechanisms are still unclear. Here, we show that the scaffold protein Rack1 plays dual roles in Hh signaling. In the absence of Hh, Rack1 promotes Ci and Cos2 to form a Ci–Rack1–Cos2 complex, culminating in Slimb-mediated Ci proteolysis. In the presence of Hh, Rack1 dissociates from Ci–Rack1–Cos2 complex and forms a trimeric complex with Smo and Usp8, leading to Smo deubiquitination and cell surface accumulation. Furthermore, we find the regulation of Rack1 on Hh pathway is conserved from Drosophila to mammalian cells. Our findings demonstrate that Rack1 plays dual roles during Hh signal transduction and provide Rack1 as a potential drug target for Hh-related diseases.

scholarly journals The Cell Type–Specific Functions of miR-21 in Cardiovascular Diseases

2020 ◽  
Vol 11 ◽  
Author(s):  
Beibei Dai ◽  
Feng Wang ◽  
Xiang Nie ◽  
Hengzhi Du ◽  
Yanru Zhao ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Vascular System ◽  
Cardiac Fibroblasts ◽  
Pressure Overload ◽  
Cell Type ◽  
Physiological Processes ◽  
A Cell ◽  
Cell Type Specific ◽  
Underlying Mechanisms ◽  
Endothelial Nitric Oxide

Cardiovascular diseases are one of the prime reasons for disability and death worldwide. Diseases and conditions, such as hypoxia, pressure overload, infection, and hyperglycemia, might initiate cardiac remodeling and dysfunction by inducing hypertrophy or apoptosis in cardiomyocytes and by promoting proliferation in cardiac fibroblasts. In the vascular system, injuries decrease the endothelial nitric oxide levels and affect the phenotype of vascular smooth muscle cells. Understanding the underlying mechanisms will be helpful for the development of a precise therapeutic approach. Various microRNAs are involved in mediating multiple pathological and physiological processes in the heart. A cardiac enriched microRNA, miR-21, which is essential for cardiac homeostasis, has been demonstrated to act as a cell–cell messenger with diverse functions. This review describes the cell type–specific functions of miR-21 in different cardiovascular diseases and its prospects in clinical therapy.

scholarly journals Melatonin Promotes the Proliferation of Chicken Sertoli Cells by Activating the ERK/Inhibin Alpha Subunit Signaling Pathway

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1230 ◽  
Author(s):  
Ke Xu ◽  
Jun Wang ◽  
Hongyu Liu ◽  
Jing Zhao ◽  
Wenfa Lu
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Sertoli Cells ◽  
Cell Counting ◽  
Erk Signaling ◽  
Alpha Subunit ◽  
Nuclear Antigen ◽  
Physiological Processes ◽  
Underlying Mechanisms ◽  
And Function

Melatonin influences physiological processes such as promoting proliferation and regulating cell development and function, and its effects on chicken Sertoli cells are unknown. Therefore, we investigated the effects of melatonin on cell proliferation and its underlying mechanisms in chicken Sertoli cells. Chicken Sertoli cells were exposed to varying melatonin concentrations (1, 10, 100, and 1000 nM), and the melatonin-induced effects on cell proliferation were measured by Cell Counting Kit 8 (CCK-8), 5-ethynyl-2’-deoxyuridine (EdU), real-time qPCR, and western blotting. We found that 1000 nM melatonin significantly (p < 0.05) promoted cell proliferation in chicken Sertoli cells. Furthermore, melatonin significantly (p < 0.05) increased the expression of inhibin alpha subunit (INHA), and the silencing of INHA reversed the melatonin-induced effects on Sertoli cell proliferation. We also found that melatonin activates the extracellular-regulated protein kinase (ERK) signaling pathway. To explore the role of the ERK signaling pathway in melatonin-induced cell proliferation, PD98059 (an inhibitor of EKR1/2) was used to pre-treat chicken Sertoli cells. The melatonin-induced proliferation of chicken Sertoli cells was reversed by PD98059, with decreased cell viability, weakened cell proliferation, and down-regulated expression of the proliferating cell nuclear antigen (PCNA), cyclin D1 (CCND1) and INHA. In summary, our results indicate that melatonin promotes the proliferation of chicken Sertoli cells by activating the ERK/inhibin alpha subunit signaling pathway.

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