Uterine distension differentially affects remodelling and distensibility of the uterine vasculature in non-pregnant rats

During pregnancy the mammalian uterine circulation undergoes significant expansive remodelling necessary for normal pregnancy outcome. The underlying mechanisms are poorly defined. The goal of this study was to test the hypothesis that myometrial stretch actively stimulates uterine vascular remodelling by developing a new surgical approach to induce unilateral uterine distension in non-pregnant rats. Three weeks after surgery, which consisted of an infusion of medical-grade silicone into the uterine lumen, main and mesometrial uterine artery and vein length, diameter and distensibility were recorded. Radial artery diameter, distensibility and vascular smooth muscle mitotic rate (Ki67 staining) were also measured. Unilateral uterine distension resulted in significant increases in the length of main uterine artery and vein and mesometrial segments but had no effect on vessel diameter or distensibility. In contrast, there were significant increases in the diameter of the radial arteries associated with the distended uterus. These changes were accompanied by reduced arterial distensibility and increased vascular muscle hyperplasia. In summary, this is the first report to show that myometrial stretch is a sufficient stimulus to induce significant remodelling of uterine vessels in non-pregnant rats. Moreover, the results indicate differential regulation of these growth processes as a function of vessel size and type.

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Reduced NO signaling during pregnancy attenuates outward uterine artery remodeling by altering MMP expression and collagen and elastin deposition

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00519.2011 ◽

2011 ◽

Vol 301 (4) ◽

pp. H1266-H1275 ◽

Cited By ~ 18

Author(s):

Sarah A. Hale ◽

Lindsey Weger ◽

Maurizio Mandala ◽

George Osol

Keyword(s):

Nitric Oxide ◽

Uterine Artery ◽

Vascular Wall ◽

Female Rats ◽

Uterine Arteries ◽

Tissue Inhibitors Of Metalloproteinase ◽

No Signaling ◽

Underlying Mechanisms ◽

Uterine Circulation ◽

Endothelial Nitric Oxide

Recent findings indicate that endothelial nitric oxide (NO) plays a key role in uterine artery outward circumferential remodeling during pregnancy. Although the underlying mechanisms are not known, they likely involve matrix metalloproteinases (MMPs). The goal of this study was to examine the linkage among NO inhibition, expansive remodeling, and MMP expression within the uterine vascular wall. Adult female rats were treated with NG-nitro-l-arginine methyl ester [l-NAME (LPLN)] beginning on day 10 of pregnancy and until death at day 20 and compared with age-matched controls [late pregnant (LP)]. Mean arterial pressure of LPLN rats was significantly higher than controls. LPLN fetal and placental weights were significantly reduced compared with controls. Main uterine arteries (mUA) were collected to determine dimensional properties (lumen area and wall thickness), collagen and elastin content, and levels of endothelial nitric oxide synthase (eNOS) and MMP expression. Circumferential remodeling was attenuated, as evidenced by significantly smaller lumen diameters. eNOS RNA and protein were significantly (>90%) decreased in the LPLN mUA compared with LP. Collagen and elastin contents were significantly increased in LPLN rats by ∼10 and 25%, respectively, compared with LP ( P < 0.05). Both MMP-2 and tissue inhibitors of metalloproteinase-2 as assessed by immunofluorescence were lower in the endothelium (reduction of 60%) and adventitia (reduction of 50%) of LPLN compared with LP mUA. Membrane bound MMP-1 (MT1-MMP) as assessed by immunoblot was significantly decreased in LPLN. These data suggest a novel contribution of MMPs to gestational uterine vascular remodeling and substantiate the linkage between NO signaling and gestational remodeling of the uterine circulation via altered MMP, TIMP-2, and MT1-MMP expression and activity.

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THE PARATHYROIDS IN CORTICOSTEROID-TREATED PREGNANT RATS AND THEIR OFFSPRING

Acta Endocrinologica ◽

10.1530/acta.0.0530547 ◽

1966 ◽

Vol 53 (4) ◽

pp. 547-552 ◽

Cited By ~ 1

Author(s):

C. Göran Hansson ◽

Lennart Angervall

Keyword(s):

Mitotic Rate ◽

Pregnant Rats

ABSTRACT Geometrically increasing doses of cortisone (0.5, 1.5 and 4.5 mg twice daily) were injected into pregnant rats, and the volume, nuclear diameters and mitotic rate of the maternal parathyroids as well as the parathyroid volume and mitotic rate in the foetuses were determined. The nuclear diameters were if anything smaller and the mitotic rate tended to decrease in the cortisone treated groups. There were no significant differences between the parathyroid volumes of the foetuses in the control and cortisone-treated groups. Thus, it seems that the development of the rat foetal parathyroids and the morphology of the maternal parathyroids are little affected if at all, by cortisone.

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Maternal Neutrophil Depletion Fails to Avert Systemic Lipopolysaccharide-Induced Early Pregnancy Defects in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms22157932 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7932

Author(s):

Sourav Panja ◽

John T. Benjamin ◽

Bibhash C. Paria

Keyword(s):

Early Pregnancy ◽

Normal Pregnancy ◽

Mrna Levels ◽

Interesting Approach ◽

Blastocyst Implantation ◽

Neutrophil Depletion ◽

Underlying Mechanisms ◽

Myd88 Signaling ◽

Induced Defects ◽

Dose Dependent

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.

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Altered offspring neurodevelopment in an arginine vasopressin preeclampsia model

Translational Psychiatry ◽

10.1038/s41398-021-01205-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Serena Banu Gumusoglu ◽

Akanksha Sri Satya Chilukuri ◽

Benjamin Wen Qing Hing ◽

Sabrina Marie Scroggins ◽

Sreelekha Kundu ◽

...

Keyword(s):

Arginine Vasopressin ◽

Ventricular Zone ◽

Vessel Diameter ◽

Female Offspring ◽

Cell Number ◽

Differentially Expressed ◽

Adult Males ◽

Social Approach ◽

Caudate Putamen ◽

Underlying Mechanisms

AbstractPreeclampsia is a severe gestational hypertensive condition linked to child neuropsychiatric disorders, although underlying mechanisms are unclear. We used a recently developed, clinically relevant animal model of preeclampsia to assess offspring. C57BL/6J mouse dams were chronically infused with arginine vasopressin (AVP) or saline (24 ng/h) throughout pregnancy. Adult offspring were behaviorally tested (Y-maze, open field, rotarod, social approach, and elevated plus maze). Offspring brain was assessed histologically and by RNA sequencing. Preeclampsia-exposed adult males exhibited increased anxiety-like behavior and social approach while adult females exhibited impaired procedural learning. Adult AVP-exposed males had reduced total neocortical volume. Adult AVP-exposed females had increased caudate–putamen volume, increased caudate–putamen cell number, and decreased excitatory synapse density in hippocampal dentate gyrus (DG), CA1, and CA3. At postnatal day 7 (P7), AVP-exposed male and female offspring both had smaller neocortex. At P7, AVP-exposed males also had smaller caudate–putamen volume, while females had increased caudate–putamen volume relative to neocortical size. Similar to P7, E18 AVP-exposed offspring had smaller dorsal forebrain, mainly in reduced intermediate, subventricular, and ventricular zone volume, particularly in males. Decreased volume was not accounted for by cell size or cerebrovascular vessel diameter changes. E18 cortical RNAseq revealed 49 differentially-expressed genes in male AVP-exposed offspring, over-representing cytoplasmic translation processes. In females, 31 genes were differentially-expressed, over-representing collagen-related and epithelial regulation pathways. Gene expression changes in E18 AVP-exposed placenta indicated potential underlying mechanisms. Deficits in behavior and forebrain development in this AVP-based preeclampsia model were distinctly different in males and females, implicating different neurobiological bases.

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Uterine artery Doppler measurement and pro-inflammatory cytokines in normal pregnancy

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2005.10.658 ◽

2005 ◽

Vol 193 (6) ◽

pp. S165

Author(s):

Jennifer Donnelly ◽

Sharon Cooley ◽

Joanna Balding ◽

Ciaran Murphy ◽

Tom Walsh ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Uterine Artery ◽

Normal Pregnancy ◽

Doppler Measurement ◽

Uterine Artery Doppler ◽

Pro Inflammatory Cytokines

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Maternal Uterine Vascular Remodeling During Pregnancy

Physiology ◽

10.1152/physiol.00033.2008 ◽

2009 ◽

Vol 24 (1) ◽

pp. 58-71 ◽

Cited By ~ 183

Author(s):

George Osol ◽

Maurizio Mandala

Keyword(s):

Extracellular Matrix ◽

Blood Flow ◽

Vascular Remodeling ◽

Normal Pregnancy ◽

Uterine Blood Flow ◽

Growth And Remodeling ◽

Cellular Mechanisms ◽

Cellular Processes ◽

Uteroplacental Blood Flow ◽

Uterine Circulation

Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodeling of the entire uterine circulation, as well as the creation of a new fetal vascular organ: the placenta. The process of remodeling involves a number of cellular processes, including hyperplasia and hypertrophy, rearrangement of existing elements, and changes in extracellular matrix. In this review, we provide information on uterine blood flow increases during pregnancy, the influence of placentation type on the distribution of uterine vascular resistance, consideration of the patterns, nature, and extent of maternal uterine vascular remodeling during pregnancy, and what is known about the underlying cellular mechanisms.

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MORPHOLOGICAL CHANGES IN THE ENDOCRINE PANCREAS IN PREGNANT RATS WITH EXPERIMENTAL DIABETES

Journal of Endocrinology ◽

10.1677/joe.0.0800175 ◽

1979 ◽

Vol 80 (2) ◽

pp. 175-179 ◽

Cited By ~ 14

Author(s):

F. A. VAN ASSCHE ◽

L. AERTS ◽

W. GEPTS

Keyword(s):

Endocrine Pancreas ◽

Experimental Diabetes ◽

Morphological Changes ◽

Normal Pregnancy ◽

Β Cells ◽

Pregnant Rats ◽

Pregnant Rat ◽

Human Pregnancy ◽

The Individual

This present study has demonstrated that during normal pregnancy in the rat the number of β-cells is increased (hyperplasia) and the volume of the individual β-cells is increased (hypertrophy). During experimental diabetes, however, the endocrine pancreas has an impaired capacity to compensate during pregnancy. In the experimental diabetic pregnant rat the β-cells cannot replicate due to the unfavourable metabolic environment. This could reflect the complications caused by diabetes during human pregnancy.

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Pregnancy decreases immunoreactive parathyroid hormone level in rats with chronic renal failure

Clinical Science ◽

10.1042/cs0960427 ◽

1999 ◽

Vol 96 (4) ◽

pp. 427-430 ◽

Cited By ~ 4

Author(s):

M. BLUM ◽

Y. WEISMAN ◽

S. TURGEMAN ◽

S. CABILI ◽

Y. WOLLMAN ◽

...

Keyword(s):

Renal Failure ◽

Parathyroid Hormone ◽

Chronic Renal Failure ◽

Virgin Female ◽

Normal Pregnancy ◽

High Serum ◽

Female Rats ◽

Pregnant Rats ◽

Serum Ipth ◽

Immunoreactive Parathyroid Hormone

Normal pregnancy is associated with an increase in serum parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol). The effect of pregnancy on these hormones in chronic renal failure (CRF) is unknown. The present work was undertaken to study the changes of serum immunoreactive parathyroid hormone (iPTH) and calcitriol in pregnant rats with CRF. The following experimental groups were studied: CRF1 (5/6 nephrectomized virgin female rats), CRF2 (5/6 nephrectomized pregnant rats at day 20–21 of pregnancy), CRF3 (5/6 nephrectomized rats 2 weeks after delivery) and their respective sham-operated control groups: N1, N2 and N3. The 5/6 nephrectomy (CRF1) resulted in renal failure with very high serum iPTH (100±18 pg/ml) and low calcitriol levels (10.6±4.3 pg/ml) compared with normal rats [N1: 14±2.5 pg/ml (P< 0.001) and 18.2±4.2 pg/ml (P< 0.01) respectively]. The pregnancy in CRF rats (CRF2) resulted in normalization of serum iPTH levels (18.2±5.41 pg/ml), which was associated with a parallel increase in serum calcitriol (29.4±8.0 pg/ml) similar to that in pregnancy of normal rats (N2). Two weeks after delivery the CRF rats (CRF3) once again had high serum iPTH (87±17 pg/ml) and low calcitriol levels (9.3±1.2 pg/ml), similar to those observed in non-pregnant uraemic rats (CRF1). It is concluded that pregnancy decreases serum iPTH in 5/6 nephrectomized CRF rats most probably by the increased level of calcitriol synthesized by the feto-placental unit.

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