Innervation of the placenta and uterus: competition between cytotrophoblasts and nerves?

In normal pregnancy, invasion of the uterus by trophoblasts is followed by dramatic elimination of the rich uterine innervation present in the non-pregnant state, and by remodeling of maternal spiral arteries. In general, the healthy survival of vascular smooth muscle requires innervation, but whether denervation plays a role in stripping of vascular smooth muscle from spiral arteries in normal pregnancy has not been explored. We propose that the temporal and spatial association of trophoblast invasion with denervation in pregnancy may involve competitive interaction between the invading trophoblast and persisting neurons. We suggest feasible experiments to explore the possible effects of such trophoblast-nerve competition on spiral artery remodeling.

Increased nerve fibers in placental bed myometrium in women with preeclampsia.

Narrowing of the uterine spiral arterioles below the deciduomyometrial junction is 1 of the key pathophysiological changes in women with preeclampsia. The contribution of pelvic autonomic nerves to decidualization and impaired placentation in preeclampsia is not clear. Placental bed biopsies were obtained from 10 women with preeclampsia and 23 nornotensive women at caesarean section. We stained them with anti-S100 and CD34 antibodies to detect the presence of nerve fibers and blood vessels, respectively. We detected S100-immunoactive nerve fibers in the myometrium but not in the decidua in both groups of women. S100-immunoactive nerve fiber density in the placental bed myometrium was significantly increased in women with preeclampsia compared to normotensive women. There was no clear relationship between the densities of nerve fibers and CD34-positive blood vessels in these biopsies. These results suggest increased nerve fibers in the placental bed myometrium may play a role in the pathogenesis of the preeclampsia.

Restricted innervation of uterus and placenta during pregnancy: evidence for a role of the repelling signal Semaphorin 3A.

Because data from the literature suggest a lack of innervation of the placenta, we have investigated placenta, umbilical cord, and uterus to identify the molecules that play a role in regulating innervation in these organs. Neuropilin-1 and Plexin-A1 are cell surface proteins that form a receptor complex for Semaphorin 3A (Sema 3A), a secreted molecule mediating repelling signals for axonal growth cones. We have analyzed the expression of Neuropilin-1, Plexin-A1, and Semaphorin 3A in the above-mentioned tissues on the hypothesis that these molecules could regulate innervation in these organs during gestation. We found that nervous fibers are only present in the proximal part of the umbilical cord, close to the newborn, and in nongestational uterine tissues. In contrast, nervous fibers are not present in the distal segment of the umbilical cord, in the placenta and in the uterine tissues during gestation. We also found that Sema 3A receptors, Neuropilin-1 and Plexin-A1, are expressed by the nervous fibers of the proximal part of the umbilical cord, whereas Sema 3A is secreted in the umbilical cord, in the placenta, and in gestational uterine tissues. We report that a factor secreted in the umbilical cord induces the collapse of neurite growth cones in vitro and provide evidence that this factor is Sema 3A. In summary, our results suggest that the chemorepulsive signals mediated by Sema 3A play an important role in preventing nerve fibers growth in the umbilical cord and in gestational uterine tissues. The inhibition of nerve growth into the myometrium as well as into the placenta could be considered fundamental processes to preserve the fetus from external stressful events.

Human placental cholinergic system.

The occurrence of acetylcholine (ACh)-like activity in human placenta, a tissue without innervation, has been known for more than 60 years. However, the non-neuronal functions of ACh in human placenta are not clearly understood. The components of the cholinergic system-ACh, choline acetyltransferase, acetylcholinesterase, butyrylcholinesterase, muscarinic receptors, and nicotinic receptors--in human placenta have been demonstrated by unequivocal methods. Primate placentae store and release ACh by mechanisms similar to those of nervous tissue. However, there are many gaps in our knowledge, which include: (a) endogenous quaternary ammonium compounds other than ACh in human placental extracts; (b) the specificity of placental enzymes; (c) the subtypes and structures of placental muscarinic and nicotinic receptors; and (d) the significance of placental alpha-bungarotoxin binding proteins, ACh receptor stimulation-cellular signaling by second messengers, and activation of immediate early target genes (C-fos, C-jun) encoding transcription factors. Several hypothetical non-neuronal functions of ACh in placenta have been postulated based upon available experimental evidence. These include: (a) regulation of blood flow and fluid volume in placental vessels; (b) opening and closing of trophoblastic channels; (c) induction of contractile properties to myofibroblasts; (d) facilitation of amino acid transport necessary for fetal growth across placenta; (e) release of placental hormones; and (f) modulation of the formation of myometrial and placental prostaglandins in human parturition. All of these roles are reasonable, and some of these roles mav turn out to be linked to one another to influence or maintain placental function.

[Nervous system of the extraembryonic organs of the white rat fetus]. / Nervnyi apparat vnezarodyshevykh organov plodov belykh krys.

Nervous apparatuses of the fetal membranes have been studied in white rats on the 18th-19th days of embryogenesis. Experimental hypoxia, novocaine and potassium chloride solutions effect ensure better revealing of the nervous system elements. At supravital staining with mythelene blue and at impregnation with silver nitrate, nervous fibers are revealed in the distal part of the umbilical cord and in the placental chorional plate. In the labyrinth part of the placenta certain nervous terminals are revealed. In the amnion certain nervous fibers and terminals are found both in the connective tissue and in the epithelium. On the omphaloplacenta vessels numerous nervous apparatuses are detected. A conclusion is made that at the end of embryogenesis the fetal membranes in the white rats are abundantly innervated. This demonstrates nervous regulation of the fetal membranes functions and of interrelationships of the fetus and the maternal organism.

Neurohistochemical evidence supporting an absence of adrenergic and cholinergic innervation in the human placenta and umbilical cord.

Neurohistochemical techniques were used to determine the distribution of adrenergic and cholinergic nerves in the human placenta and the umbilical cord adjacent to the chorion. These morphologic studies demonstrate the absence of neural elements in these sites. The significance of these findings to the placental innervation controversy is discussed.