Expression of nerve growth factor and its receptors in the uterus of rabbits: functional involvement in prostaglandin synthesis

Maranesi, Margherita; Parillo, Francesco; Leonardi, Leonardo; Rebollar, Paloma García; Alonso, Beatriz; Petrucci, Linda; Gobbetti, Anna; Boiti, Cristiano; Arruda-Alencar, J; Moura, Arlindo de Alencar Araripe; Zerani, Massimo

doi:10.1016/j.domaniend.2016.02.001

Cited by 26 publications

(22 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NGF, GDNF, and BDNF are the three most abundant neurotrophins existing in the adult brain [54]. These neurotrophins are also highly expressed in the female reproductive system and exert their biological roles in uterine growth and proliferation [55, 56]. In this study, we found that OVX caused a widespread decrease in the expression levels of the three neurotrophins in the prefrontal cortex, hippocampus, and uterus.…”

Section: Discussionmentioning

confidence: 57%

Total Polysaccharides of Lily Bulb Ameliorate Menopause-Like Behavior in Ovariectomized Mice: Multiple Mechanisms Distinct from Estrogen Therapy

Zhou

Zheng

Sharma

et al. 2019

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Our previous study has demonstrated the effects of aqueous extract of lily bulb in alleviating menopause-related psychiatric symptoms in ovariectomized (OVX) mice. This study sought to further investigate the psychotropic effects of total polysaccharides of lily bulb (TPLB) against anxiety, depression, and cognitive deterioration and the underlying mechanisms in OVX mice using behavioral, neurochemical, molecular, and proteomic approaches in comparison with estrogen therapy. While TPLB and estradiol showed similar effects in reducing OVX-induced anxiety, depression, and cognitive impairment, the psychotropic effects of TPLB were more closely associated with the predominant activation of estrogen receptors (ERs) and regulation of brain regional neurotransmitters and neurotrophins with minor effects on the uterus. Estradiol had similar potencies in binding affinity at ERα and ERβ, which caused widespread genetic and epigenetic effects. In contrast, TPLB displayed a higher affinity at ERβ than ERα, triggering the specific Ras/Akt/ERK/CREB signaling pathway without affecting any epigenetic activity. TPLB additionally modulated multiple proteins associated with mitochondrial oxidative stress, but estradiol did not. These results indicate that TPLB has comparable efficacy in reducing menopause-associated neuropsychological symptoms with a better safety profile compared to estrogen therapy. We suggest that TPLB could serve as a novel agent for menopause syndrome.

show abstract

Section: Discussionmentioning

confidence: 57%

Total Polysaccharides of Lily Bulb Ameliorate Menopause-Like Behavior in Ovariectomized Mice: Multiple Mechanisms Distinct from Estrogen Therapy

Zhou

Zheng

Sharma

et al. 2019

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…However, in more recent studies this neuropeptide has been also identified as an ovulation-inducing factor (OIF) present in the seminal plasma (SP) of some reflex ovulating species such as camelids or rabbits [2–5]. In rabbits, the neuropeptide and its receptors (TrkA and p75) have been identified in all male and female reproductive tissues (testes, epididymis and accessory glands [6–10], SP [7, 8, 10, 11], uterus, oviduct and ovary [12–14]). While some studies have suggested a role of β-NGF in the mechanism of ovulation in rabbits [8, 12, 15], evidence of its role as an OIF in this species, as found in camelids, is still scarce.…”

Section: Introductionmentioning

confidence: 99%

“…In rabbits, the neuropeptide and its receptors (TrkA and p75) have been identified in all male and female reproductive tissues (testes, epididymis and accessory glands [6–10], SP [7, 8, 10, 11], uterus, oviduct and ovary [12–14]). While some studies have suggested a role of β-NGF in the mechanism of ovulation in rabbits [8, 12, 15], evidence of its role as an OIF in this species, as found in camelids, is still scarce. Further, while the intramuscular administration of mouse β-NGF [8] or rabbit SP [3, 16] has been unsuccessful for inducing ovulation, an ovarian response in terms of increased numbers of hemorrhagic follicles (non-ruptured blood-filled anovulatory follicles) has been observed.…”

Section: Introductionmentioning

confidence: 99%

Recombinant rabbit beta nerve growth factor production and its biological effects on sperm and ovulation in rabbits

et al. 2019

View full text Add to dashboard Cite

In some induced-ovulating species, beta nerve growth factor (β-NGF) has important roles in ovulation, though data for rabbits are still inconclusive. In this study we first synthesized functional recombinant β-NGF from rabbit tissue (rrβ-NGF) to address the following objectives: 1) to compare rabbit β-NGF amino acid sequence with those of other induced- or spontaneous-ovulating species; 2) to assess the effects of rrβ-NGF on rabbit sperm viability and motility, and 3) to examine the in vivo ovulation inducing effect of rrβ-NGF added to the seminal dose in rabbit does. The NGF gene in rabbit prostate tissue was sequenced by Rapid Amplification of cDNA Ends and annotated in GenBank (KX528686). Recombinant rβ-NGF was produced in CHO cells and purified by affinity chromatography. Once confirmed by Western blotting and mass spectrometry (MALDI-TOF) that the amino acid sequence of the recombinant protein corresponded to β-NGF, its functionality was validated in PC12 cells in a successful dose-response study over 8 days. The amino acid sequence of prostate rabbit NGF differed to that of other species mainly in its receptor binding sites. In all the spontaneous ovulating species examined, compared with rabbit, alanine and proline residues, which interact with the high-affinity receptor, were replaced by a serine. In rabbits, asparagine and methionine were substituted by lysine at the low-affinity receptor binding site. In time- and dose-response experiments, the in vitro addition of rrβ-NGF to the ejaculate did not affect sperm viability whereas sperm motility parameters were enhanced by the addition of 1 μg/mL of the neuropeptide. Addition of this same concentration of rrβ-NGF to the seminal dose administered via the intravaginal route in does induced ovulation with a delayed LH peak, leading to a plasma progesterone increase, gestation and delivery. Our findings suggest that rrβ-NGF could be a useful option for biotechnological and reproduction assisted techniques in rabbits but further studies are needed.

show abstract

“…On the other hand, NGF expression is present in epithelial and stromal cells in the rabbit uterus (81), as well as in human uterus (82), but its expression is lower than in the ovary (13). In addition, NGF expression seems to be necessary to ensure maternal tolerance in healthy pregnancies in mice, but an excess of NGF results in fetal rejection due to exacerbated inflammation (83).…”

Section: Role Of Neurotrophins In Gynecological Cancer Angiogenesis: mentioning

confidence: 99%

Angiogenesis in Gynecological Cancers: Role of Neurotrophins

et al. 2019

View full text Add to dashboard Cite

Angiogenesis, or generation of new blood vessels from other pre-existing, is a key process to maintain the supply of nutrients and oxygen in tissues. Unfortunately, this process is exacerbated in pathologies such as retinopathies and cancers with high angiogenesis as ovarian cancer. Angiogenesis is regulated by multiple systems including growth factors and neurotrophins. One of the most studied angiogenic growth factors is the vascular endothelial growth factor (VEGF), which is overexpressed in several cancers. It has been recently described that neurotrophins could regulate angiogenesis through direct and indirect mechanisms. Neurotrophins are a family of proteins that include nerve growth factor (NGF), brain-derived growth factor (BDNF), and neurotrophins 3 and 4/5 (NT 3, NT 4/5). These molecules and their high affinity receptors (TRKs) regulate the development, maintenance, and plasticity of the nervous system. Furthermore, it was recently described that they display essential functions in non-neuronal tissues, such as reproductive organs among others. Studies have shown that several types of cancer overexpress neurotrophins such as NGF and BDNF, which might contribute to tumor progression and angiogenesis. Besides, in recent years the FDA has approved the use of pharmacologic inhibitors of pan-TRK receptors in patients with TRKs fusion-positive cancers. In this review, we discuss the mechanisms by which neurotrophins stimulate tumor progression and angiogenesis, with emphasis on gynecological cancers.

show abstract

Expression of nerve growth factor and its receptors in the uterus of rabbits: functional involvement in prostaglandin synthesis

Cited by 26 publications

References 42 publications

Total Polysaccharides of Lily Bulb Ameliorate Menopause-Like Behavior in Ovariectomized Mice: Multiple Mechanisms Distinct from Estrogen Therapy

Total Polysaccharides of Lily Bulb Ameliorate Menopause-Like Behavior in Ovariectomized Mice: Multiple Mechanisms Distinct from Estrogen Therapy

Recombinant rabbit beta nerve growth factor production and its biological effects on sperm and ovulation in rabbits

Angiogenesis in Gynecological Cancers: Role of Neurotrophins

Contact Info

Product

Resources

About