In healthy human pregnancies, placental growth factor (PGF) concentrations rise in maternal plasma during early gestation, peak over Weeks 26-30, then decline. Because PGF in nongravid subjects participates in protection against and recovery from cardiac pathologies, we asked if PGF contributes to pregnancy-induced maternal cardiovascular adaptations. Cardiovascular function and structure were evaluated in virgin, pregnant, and postpartum C56BL/6-Pgf(-) (/) (-) (Pgf(-) (/) (-)) and C57BL/6-Pgf(+/+) (B6) mice using plethysmography, ultrasound, quantitative PCR, and cardiac and renal histology. Pgf(-/-) females had higher systolic blood pressure in early and late pregnancy but an extended, abnormal midpregnancy interval of depressed systolic pressure. Pgf(-/-) cardiac output was lower than gestation day (gd)-matched B6 after midpregnancy. While Pgf(-) (/) (-) left ventricular mass was greater than B6, only B6 showed the expected gestational gain in left ventricular mass. Expression of vasoactive genes in the left ventricle differed at gd8 with elevated Nos expression in Pgf(-) (/) (-) but not at gd14. By gd16, Pgf(-) (/) (-) kidneys were hypertrophic and had glomerular pathology. This study documents for the first time that PGF is associated with the systemic maternal cardiovascular adaptations to pregnancy.

Preeclampsia, a hypertensive syndrome occurring in 3-5% of human pregnancies, has lifelong health consequences for fetuses. Cognitive ability throughout life is altered, and adult stroke risk is increased. One potential etiological factor for altered brain development is low concentrations of proangiogenic placental growth factor (PGF). Impaired PGF production may promote an antiangiogenic fetal environment during neural and cerebrovascular development. We previously reported delayed vascularization of the hindbrain, altered retinal vascular organization, and less connectivity in the circle of Willis in Pgf mice. We hypothesized Pgf mice would have impaired cognition and altered brain neuroanatomy in addition to compromised cerebrovasculature. Cognitive behavior was assessed in adult Pgf and Pgf mice by four paradigms followed by postmortem high-resolution MRI of neuroanatomy. X-ray microcomputed tomography imaging investigated the three-dimensional cerebrovascular geometry in another cohort. Pgf mice exhibited poorer spatial memory, less depressive-like behavior, and superior recognition of novel objects. Significantly smaller volumes of 10 structures were detected in the Pgf compared with Pgf brain. Pgf brain had more total blood vessel segments in the small-diameter range. Lack of PGF altered cognitive functions, brain neuroanatomy, and cerebrovasculature in mice. Pgf mice may be a preclinical model for the offspring effects of low-PGF preeclampsia gestation.

Uterine natural killer (uNK) cells are the dominant lymphocytes of pregnant mammals' uterus. Studies have identified four differentiation stage of mouse uNK cells based on Dolichos biflorus lectin cytochemistry, and their distribution showed preferential domain in the uterus through out the pregnancy. This work was done to investigate the expression of alpha5, alpha6, and beta7 integrins on uNK cells and their ligands distribution. Section of mouse uterus from sixth to seventeenth gestational days were submitted to immunocytochemistry and positive reactions for alpha5, alpha6, and beta7 integrins were found on uNK from eighth to tenth gestational days but not after twelfth gestational days. Fibronectin reactions were seemed from sixth to tenth gestational days around uNK from the myometrium and endometrium close to the myometrium. No reaction for fibronectin was seen in the decidualized and nondecidualized endometrium near the placenta. Laminin reaction was seen just in the antimesometrial side. beta7 integrin seems to be the active receptor to bind with VCAM-1 or MAdCAM-1 of endothelial cells, promoting the uNK cross through the vessels. The absence of laminin in an uNK domain suggests these cells are not dependent of laminin and alpha6 integrin for their establishment. However, fibronectin seems to support uNK migration, proliferation, differentiation, and survival in the uterus by binding with alpha5 integrin. The loss of alpha5 integrin ligation by the down regulation of fibronectin could inhibits these events and further studies are need to investigate whether unligated alpha5 can actively and initiate apoptosis, maybe in a caspase 8-dependent way that has been called integrin-mediated death.

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Uterine natural killer (uNK) cells are the dominant lymphocytes found in pregnant mammals that develop uterine decidualization.

Introduction: Androgenic anabolizing steroids (AAS) are a group of natural and synthetic compounds deriving from testosterone or one of its sub-products which are more and more used by young people for improving physical performance or for aesthetic reason. Complications, such as arteriosclerosis and acute myocardium infarction (AMI), have been reported in AAS' users, but the records about the ventricular anatomical structure of those users are few. Because of that, this study aimed to verify morphologic and quantitative morphometric possible alterations on mice's left ventricular myocardium submitted to their use. Materials and Methods: Thirty mice were divided into three 10-animals groups (group 1: received Deca-Durabolin  ; group 2: received Potenay  ; and group 3: received saline solution), each one of them composed by five males and five females, treated once a week and put to swimming thrice a week during one month. Results: Results revealed that there were no significant alterations in the quantity of muscle fibers in the animals treated with AAS but there were significant differences when comparing male-to-female mice and left ventricular area (µm2). It was observed that mice in group 1 (Deca-Durabolin  ) presented a lesser left ventricular area when compared to those in group 3 (control) but, when analyzing cardiac muscle fibers morphologically, it was verified that the myocardium was looser and softer in drug-submitted animals, especially those in group 1 (Deca-Durabolin  ). Conclusion: There are effective significant differences when a morphologic and quantitative morphometric analysis is done concerning mice's left ventricular myocardium submitted to AAS.

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One of the most abundant immunologic cell types in early decidua is the uterine natural killer (UNK) cell that despite the presence of cytoplasmic granules rich in perforin and granzymes does not degranulate in normal pregnancy. UNK cells are important producers of angiogenic factors that permit normal dilation of uterine arteries to provide increased blood flow for the growing feto-placental unit. Gram-negative bacteria lipopolysaccharide (LPS) administration can trigger an imbalance of pro-inflammatory and anti-inflammatory cytokines impairing the normal immune cells activity as well as uterine homeostasis. The present study aimed to evaluate by immunohistochemistry the reactivity of perforin and α-actin on UNK cell from LPS-treated pregnant mice. For the first time, we demonstrate that LPS injection in pregnant mice causes α-actin down regulation, concomitantly with perforin loss in UNK cells. This suggests that LPS alters UNK cell migration and activates cytotoxic granule release.