Expression and Localization of NO Synthase Isoenzymes (iNOS and eNOS) in Development of the Rabbit Placenta

Abstract

Abstract. Nitric oxide synthase (NOS) is a key regulator of angiogenesis and embryogenesis in the mammalian reproductive process. Here, we attempted to clarify the expression and localization of inducible and endothelial NOS (iNOS and eNOS) in the developing rabbit placenta. Real-time RT-PCR analysis indicated that iNOS mRNA was significantly upregulated till the complete development of the placenta (d18), and then significantly decreased at the end of fetal growth stage (d28) during successful pregnancy. The eNOS mRNA was also enhanced in the pregnant uteri and gradually decreased near the term of pregnancy. Western blot analysis also showed elevation of the iNOS and eNOS protein levels during the course of successful pregnancy till the functional maturation of the placenta (d18). Immunohistochemical study revealed distinct localizations of iNOS along the radial arteries and eNOS at the spiral arteries and arterial sinuses in the developing placenta. This may reflect that iNOS and eNOS participate in pregnancy success through placentation-specific vascular formation and by supporting adequate blood circulation in the rabbit placenta. Key words: eNOS, iNOS, Rabbit placenta, Vascular formation (J. Reprod. Dev. 58: [231][232][233][234][235][236] 2012) I n pregnant mammals, the placenta acts as exchange interface for nutrients and waste products between the fetal and maternal circulation. The placenta is a very fast growing tissue with corresponding high metabolic demand from the embryo or fetus that requires an active blood supply and rapid vascular development [1][2][3]. Failure of placental growth during early and mid pregnancy is directly associated with inadequate uterine and umbilical blood flow, which adversely affects transportation of fetal nutrients [4]. Extensive increase of the transplacental exchange during the last half of gestation is closely dependent upon the dramatic growth of the vascular architecture and the resultant large volume of uterine and umbilical blood flow [1].Nitric oxide (NO), a multifunctional biomolecule, is produced from the essential amino acid L-arginine via nitric oxide synthase (NOS), which is classified into the calcium-independent or constitutive calcium/calmodulin-sensitive isoforms. The former is represented by inducible NOS (iNOS), and the latter is represented by the endothelial and neuronal NOS (eNOS and nNOS) [5]. NO plays crucial roles in the mediation of a wide variety of physiological processes including vasodilation, angiogenesis, platelet aggression, immune functions, connective tissue remodeling and smooth muscle activity [6]. iNOS and eNOS are known to dynamically regulate normal physiological events during successful pregnancy such as ovulation, implantation, trophoblast invasion, placental formation, fetal development and delivery [7][8][9].In the developing placenta, specific vascular formation occurs through the processes of destruction of preexisting vessels, de novo angiogenesis and convergence of blood path in association with the invitation of plenty ...

Improvements in the conception rate, milk composition and embryo quality of rabbit does after dietary enrichment with n-3 polyunsaturated fatty acids

“…Other positive result obtained in the current study was that pregnant animals fed enriched diet showed increased plasma progesterone concentrations at 7 and 14 days of pregnancy. In this period, embryo implantation and immediately placenta formation occur (Khan et al, 2012), therefore, the higher the progesterone concentrations, the better implantation and placentation process would take place, with an improved survival post-implantation of foetuses (Froment et al, 2006). In this regard, similar progesterone results have been obtained in previous work (Rebollar et al, 2014) at 7 days of pregnancy and in additional trials with the same supplement (Rodríguez et al, 2016) we have observed more born alive in enriched does.…”

“…Nonetheless, although there were no differences in the weight of neonates, PUFA supplementation had a favourable effect on the individual kits body size. That was evident the day of parturition, probably due to the higher plasma progesterone concentration when placenta formation occurs (Khan et al, 2012). In this connection, several evidences from animals and humans suggest that the dietary n-3 PUFA during pregnancy promotes early neural and retinal tissues development and regulates behavioural and neurochemical aspects related to stress responses, growth and cognitive functions, being very important in order to vitality of newborns (Bernardi et al, 2012).…”

The effects of sildenafil citrate on feto–placental development and haemodynamics in a rabbit model of intrauterine growth restriction

“…has a high expression level of NOS, especially NOS3 (Khan et al 2012), which may facilitate sildenafil citrate function. Both processes would be expected to stimulate neoangiogenesis and may also improve maternal blood flow to the placenta, thereby facilitating nutrient and oxygen delivery to the fetus.…”

Competition for Materno-Fetal Resource Partitioning in a Rabbit Model of Undernourished Pregnancy

“…In this sense, lipid peroxides and oxygen radicals can alter endothelial cells, resulting in fibrin deposition in the vessel walls [67]. Consequently, the arterial sinuses system in the rabbit, which can be identified within this period of gestation [78] and is responsible to retain maternal blood flow and then supply it to fetal area could be altered, resulting in IUGR. On the other hand, the reduction in decidua size could be a mechanism of these placentas to support fetal demands for growth by depletion of their glycogen reserves allocated in the small uninucleated cells of this placental section [79], and therefore may explain the increase in placental efficiency and the reduction in weight.…”