Nitric oxide synthase distribution during implantation in the mouse

Abstract

The peri-implantation period is a critical time during murine development. Although the importance of nitric oxide has been demonstrated during gestation, its role in implantation has not been fully defined. The aim of this study was to quantify (by Western blotting) two prominent nitric oxide synthase (NOS) isoforms, inducible (iNOS) and endothelial (eNOS) and localize all three forms [iNOS, eNOS, and neuronal (nNOS)] by immunohistochemistry in uterine tissue from days 4 through 8 of pregnancy. By day 6, iNOS values were significantly elevated in implantation sites compared with interimplantation regions and continued to rise through day 8. Analysis of eNOS was similar, but implantation site values peaked by days 6 and 7. Labelled iNOS cells were within the decidua, around myometrial vessels, and within the ectoplacental cone. At implantation, eNOS was conspicuous, displaying label adjacent to the embryo in vessels of the primary decidual zone. nNOS was localized mainly in the mesometrium and myometrium and did not appear to change throughout the peri-implantation period. The increased iNOS and eNOS values following implantation in the embryonic site may imply roles in tissue remodelling, immunosuppression and vasoregulation. Nitric oxide may play an important role in the mechanisms of implantation where these factors are keys to successful pregnancy.

Disruption of the endothelial nitric oxide synthase gene affects ovulation, fertilization and early embryo survival in a knockout mouse model

“…This in vivo evidence confirms previous studies on the role of NOS3 in implantation (Maul et al 2003). In fact, the three NOS isoforms are present within the mouse implantation site; NOS2 and NOS3 being the most important (Purcell et al 1999). NO has been also found to be produced by preimplantation embryos; this production being required for normal embryo development (Gouge et al 1998).…”

“…Later, around 12.5-14.5 day of pregnancy, the period of transition between the stages of late embryo and early fetus occurs (Evans & Sack 1973). In the post-implantation period and early placental development, NO and NOS3 are hypothesized to be involved in tissue remodeling, immunosuppression, and vasoregulation (Purcell et al 1999), and thus contribute to maintaining vasodilatation and preventing coagulation, which are necessary for the success of the early pregnancy (Gagioti et al 2000). In the current study, differences were not found between genotypes in the morphological changes around embryo death; however, this may be related to the ultrasound machine and, specifically, to the frequency of the probes used.…”

“…Several studies have emphasized the role of NO and NOS, and specifically NOS3, in processes of ovulation, fertilization, implantation, and early embryo development (Gouge et al 1998, Purcell et al 1999, Gagioti et al 2000, Maul et al 2003, Thaler & Epel 2003.…”

Protective effects of baicalin on lipopolysaccharide (LPS)-induced implantation failure and the uterine endometrium in mice

“…All the change trends were similar between NO and IFN-with the same treatment. The study reported that NOS may be induced by IFN-or LPS (Purcell et al, 1999). The NOS activities of LPS treatment and low dose baicalin (0.1 mg) groups were high.…”

Nitric oxide modulates murine yolk sac vasculogenesis and rescues glucose induced vasculopathy

“…The importance of NO as a regulator of early developmental events has been established by studies that demonstrated that the oocyte and preimplantation embryo are exposed to NO, and oocyte maturation, preimplantation embryogenesis and implantation require NO (Biswas et al, 1998;Gagioti et al, 2000;Maul et al, 2003;Novaro et al, 1997;Purcell et al, 1999;Sengoku et al, 2001;Shukovski and Tsafriri, 1995;Telfer et al, 1995). Moreover, in vitro and in vivo studies showed that administration of either NOS inhibitors or NO donors hinders development of preimplantation embryos (i.e.…”