Brain Endothelial Cells Control Fertility through Ovarian-Steroid–Dependent Release of Semaphorin 3A

Giacobini, Paolo; Parkash, Jyoti; Campagne, Céline; Messina, Andréa; Casoni, Filippo; Vanacker, Charlotte; Langlet, Fanny; Hobo, Barbara; Cagnoni, Gabriella; Gallet, Sarah; Hanchate, Naresh K.; Mazur, Danièle; Taniguchi, Masahiko; Mazzone, Massimiliano; Verhaagen, Joost; Ciofi, Philippe; Bouret, Sébastien G.; Tamagnone, Luca; Prévot, Vincent

doi:10.1371/journal.pbio.1001808

Cited by 59 publications

(66 citation statements)

References 63 publications

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“…A study from our group has shown that in the adult rodent brain, vascular endothelial cells of the ME express and release Sema3A (fig. 4b-d) and that the amount released is regulated by the ovulatory cycle [132]. In particular, this study highlights a new mechanism through which the fenestrated endothelial cells of the ME release the 65-kDa isoform of Sema3A (p65-Sema3A) with precise timing during the ovarian cycle, being maximal during proestrus under the influence of circulating estradiol (E 2 ), and that Nrp1 is expressed in GnRH axons.…”

Section: Semaphorins and Neuroglial Plasticity In The Adult Hypothalamentioning

confidence: 97%

“…g Quantitative analysis of the percentage of GnRH nerve terminals located <1 μm from the pericapillary space in the external zone of the ME in explants from diestrous (left panel) and proestrous (right panel) rats treated with Sema3A, a Nrp1-neutralizing antibody (Nrp1-Ab) and in controls. Illustrations in b-g were adapted with permission from Giacobini et al [132]. h Schematic highlighting morphological changes in GnRH terminals and tanycytic end feet during the different phases of the ovulatory cycle.…”

Section: Semaphorins and Neuroglial Plasticity In The Adult Hypothalamentioning

confidence: 99%

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Shaping the Reproductive System: Role of Semaphorins in Gonadotropin-Releasing Hormone Development and Function

Giacobini¹

2015

Neuroendocrinology

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The semaphorin proteins, which contribute to the morphogenesis and homeostasis of a wide range of systems, are among the best-studied families of guidance cues. Much recent research has focused on the role of semaphorins in the development and adult activity of hormone systems and, reciprocally, how circulating reproductive hormones regulate their expression and function. Specifically, several reports have focused on the molecular mechanisms underlying the effects of semaphorins on the migration, survival and structural and functional plasticity of neurons that secrete gonadotropin-releasing hormone (GnRH), essential for the acquisition and maintenance of reproductive competence in mammals. Alterations in the development of this neuroendocrine system lead to anomalous or absent GnRH secretion, resulting in heterogeneous reproductive disorders such as congenital hypogonadotropic hypogonadism (CHH) or other conditions characterized by infertility or subfertility. This review summarizes current knowledge of the role of semaphorins and their receptors on the development, differentiation and plasticity of the GnRH system. In addition, the involvement of genetic deficits in semaphorin signaling in some forms of CHH in humans is discussed.

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Section: Semaphorins and Neuroglial Plasticity In The Adult Hypothalamentioning

confidence: 97%

Section: Semaphorins and Neuroglial Plasticity In The Adult Hypothalamentioning

confidence: 99%

Shaping the Reproductive System: Role of Semaphorins in Gonadotropin-Releasing Hormone Development and Function

Giacobini¹

2015

Neuroendocrinology

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“…The present study implicated the synergistic role of Nrp1 in DDR2-induced osteoblastogenesis. Together with other commence in teeth formation [31,32], wound healing [33,34], and regulation of reproductive cycle [35,36,37], it could be deduced that DDR2 and Nrp1 are not only structurally but also functionally related proteins. It is probably that DDR2 also forms complex with Nrp1 and this two molecules act in concert with each other in other aspects.…”

Section: Discussionmentioning

confidence: 99%

“…Due to the similar structural characteristics, Nrp1 has functions in common with DDR2, such as roles in angiogenesis [28,29,30], teeth formation [31,32], wound healing [33,34], and female reproductive cycle [35,36,37]. In this study, we aimed to examine the function of Nrp1 in osteoblast differentiation, and to test whether there is a close correlation between Nrp1 and DDR2.…”

Section: Introductionmentioning

confidence: 99%

Nrp1, a Neuronal Regulator, Enhances DDR2-ERK-Runx2 Cascade in Osteoblast Differentiation via Suppression of DDR2 Degradation

Zhang

Teng

Zhang

et al. 2015

Cell Physiol Biochem

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Background: Osteoblastogenesis is under delicate control by multiple factors and hormones. Recent reports indicated the involvement of immunological and neuronal regulators. However, the role of neuropilin 1 (Nrp1) in osteoblastogenesis remains obscure. Methods: Real-time PCR was carried out to detect the mRNA of osteoblastic markers, Nrp1, and discoidin domain receptor 2 (DDR2). Immunoblot was performed to test the protein of Nrp1 and DDR2. Osteogenic differentiation was evaluated by mRNA analysis of osteogenic markers, and determination of ALP activity and OCN secretion. The intercellular signaling effectors were examined by immunoblot. Immunofluorescent assays were performed to detect the localization of Nrp1 and DDR2. Half-life determination assay was executed to test the DDR2 stability. Results: The expression of Nrp1 paralleled with that of DDR2 during osteoblastogensis. Nrp1 overexpression enhanced DDR2-induced stimulation of osteoblastogensis, whereas Nrp1 silencing caused attenuation. Nrp1 overexpression increased the phosphorylation of DDR2, ERK1/2 and Runx2. Nrp1 co-localized with DDR2 in the cellular membrane of differentiated MC3T3-E1. Enhanced or attenuated Nrp1 expression did not alter the mRNA transcript of DDR2. Nrp1 overexpression prolonged the half-life of DDR2 protein. Conclusion: Our results originally demonstrated the stimulatory role of Nrp1 in DDR2-induced osteoblast differentiation, providing molecular evidence for exploiting Nrp1 and DDR2 as targets to treat bone-related disease.

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“…2). By contrast, fenestrated rat endothelial cells of the hypothalamic-hypophyseal portal vessels release semaphorin-3A, which is thought to induce GnRH neuron axonal growth and sprouting within the ME as a function of the oestrous cycle 61 . These mechanisms are likely to enable the generation of high concentrations of GnRH, which evoke the GnRH/LH surge, to be released into the pituitary portal circulation 62,63 .…”

Section: [H3] Gnrh and Lh Surge Generationmentioning

confidence: 97%

An updated view of hypothalamic–vascular–pituitary unit function and plasticity

et al. 2016

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Brain Endothelial Cells Control Fertility through Ovarian-Steroid–Dependent Release of Semaphorin 3A

Abstract: Endothelial-cell–derived Sema3A promotes axonal outgrowth and plasticity and thereby regulates neurohormone release in the adult rodent brain in response to the ovarian cycle.

Cited by 59 publications

References 63 publications

Shaping the Reproductive System: Role of Semaphorins in Gonadotropin-Releasing Hormone Development and Function

Shaping the Reproductive System: Role of Semaphorins in Gonadotropin-Releasing Hormone Development and Function

Nrp1, a Neuronal Regulator, Enhances DDR2-ERK-Runx2 Cascade in Osteoblast Differentiation via Suppression of DDR2 Degradation

An updated view of hypothalamic–vascular–pituitary unit function and plasticity

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