Endometrial injury increases side population cells in the uterine endometrium: a decisive role of estrogen.

Normal endometrial growth is essential for embryonic implantation and maintenance of pregnancy. The uterine endometrium contains stem cells that are involved in tissue regeneration. Side population cells (SP cells) are an emerging cell population that may be responsible for the regeneration process of uterine endometrium. In this study, we investigated the changes in the distribution of SP cells using a mouse model of uterine endometrial injury that was induced by peritoneal injection of lipopolysaccharide (LPS). The uterine horns were collected 0, 6, 12, and 18 hours after LPS injection. ATP-binding cassette and sub-family G member 2 (Abcg2) is highly expressed on the cellular membrane of some stem and progenitor cells, and was used as a marker for SP cells. Immunohistochemistry demonstrated that Abcg2-positive cells were increased around the uterine endometrial glands from 6 to 12 h after LPS injection. The percentage of Abcg2-positive cells was calculated using flow cytometry. The percentage of stromal SP cells was significantly higher at 6 h after LPS injection, compared with the value before the injection (3.01 ± 0.41% vs. 1.63 ± 0.31%, P < 0.05). To evaluate the influence of ovarian hormones, we implanted pellets containing 17ß-estradiol (0.1 mg), progesterone (10 mg), or a combination of 17ß-estradiol and progesterone in the bilaterally ovariectomized mice. Ovariectomy abolished the increase in SP cells, which was restored by estradiol, but not by progesterone or the combination treatment. In conclusion, estrogen is required for the increase of SP cells, thereby leading to the regeneration of the uterine endometrium.

Role of nitric oxide and reactive oxygen species in the pathogenesis of preeclampsia.

AIM: Preeclampsia is characterized by a disruption of general vascular dilatation, which is mainly mediated by nitric oxide (NO) and disturbed by reactive oxygen species (ROS). The present study investigated the roles of NO and ROS in the pathogenesis of preeclampsia. METHODS: Serum samples were obtained prospectively. Serum levels of NO(2)/NO(3) (NOx) and creatol (CTL), the oxidized metabolite of creatine, and flow-mediated dilatation (FMD) of brachial artery were measured in normal pregnant women and preeclamptic patients. To evaluate the effect of circulating factors that control vascular function NO synthase (NOS) and NAD(P)H oxidase mRNA expression was evaluated in cultured human umbilical vein endothelial cells using reverse transcriptase polymerase chain reaction. RESULTS: Serum NOx concentration was decreased and CTL concentration was increased in preeclamptic patients relative to healthy controls during the first trimester of pregnancy. Further, preeclamptic patients exhibited disrupted FMD, which was regulated in part by NO. Immunohistochemistry demonstrated strong expression of nitrotyrosine in the vasculature of preeclamptic placentas. Treatment with sera derived from preeclamptic patients increased endothelial expression of inducible NOS (iNOS) mRNA, and this increase was inhibited by angiotensin II (Ang II) receptor type 2 (AT2) blocker. Endothelial NAD(P)H oxidase subunit gp91(phox) expression was increased by treatment with sera from preeclamptic patients and this increase was attenuated by Ang II receptor type 1 (AT1) blocker. CONCLUSION: The present findings suggest that NO and ROS play important roles in the pathogenesis of preeclampsia and that these roles involve Ang II.

Detection of fetal cells in the maternal kidney during gestation in the mouse.

It has been reported that fetal cells migrate into maternal blood and organs. Since these fetal chimeric cells could be involved in maternal allogeneic tolerance to the fetus, the fetal chimeric cells might be implicated in maternal-fetal immunology and development of maternal autoimmune diseases. However, the mechanism and role of fetal microchimerism remains unclear. We aimed to describe the mechanism by which fetal cells become associated with maternal organs during pregnancy, using a mouse fetal microchimerism model. Non-obese diabetic/severe combined immunodeficiency (NOD/SCID) female mice, which are useful for tracking the behavior of fetal cells in the maternal body, were mated with transgenic males expressing enhanced green fluorescent protein (GFP), and the presence of GFP-positive cells were examined in peripheral blood and organs of pregnant mothers. By flow cytometry, we showed that 0.95 +/- 0.48% of mononuclear cells detected in the maternal peripheral blood were GFP-positive, and thus of fetal origin, during the first gestational week. This value decreased to 0.10 +/- 0.13% during the third gestational week (p < 0.05). GFP-positive cells were detected in the extraglomerular mesangial region and among the epithelial cells of the proximal renal tubule of the maternal kidney. These GFP-positive cells also expressed angiotensin II receptor subtype 2 (AT2), which is known to participate in regulating organogenesis and vasoreactivity. Fetal cells expressing AT2 may therefore be involved in the regulation of vascular tone in the maternal kidney. These observations suggest that fetal cells could influence maternal renal function through activation of the AT2 signaling.