NGF and the Male Reproductive System: Potential Clinical Applications in Infertility

Abstract

Infertility is a worldwide health issue defined by the World Health Organization (WHO) as the inability to establish a pregnancy after 12 months or more of regular and unprotected sexual intercourse. Male infertility etiology can be related to either congenital or acquired factors. The therapeutical approach to male infertility depends on the underlying causes and includes medical and surgical treatments. In recent studies, the potential role of nerve growth factor (NGF) in male reproductive physiology has been proposed. It has been hypothesized that neurotrophins might be involved in testis morphogenesis and regulation of several aspects of spermatogenesis. Moreover, it has been shown that NGF exerts its role on gonadotropin-releasing hormone (GnRH) neurons through the activation of the PKC/p–ERK1/2/p–CREB cascade, which leads to the activation of hypothalamic cells and the consequent activation of hypothalamus–pituitary–gonadal axis (HPG) with the secretion of GnRH. Lastly, it has been shown that the physiology of mature sperm is affected by both exogenous and endogenous NGF. The NGF impact on the HPG axis and its effect on GnRH neurons might be exploited in the therapy of male hypogonadism or used as a protective strategy against gonadal dysfunction related to chemotherapeutic agents. Moreover, the improving effect of NGF on sperm motility and vitality could be useful to enhance assisted reproduction outcomes. NGF could be supplemented to cryopreserved sperm samples to counteract the oxidative stress induced by the frozen and thawing processes. Indeed, the potential clinical applications of NGF in male infertility treatment have been discussed.

The role of the pediatrician in the management of the child and adolescent with gender dysphoria

“…From the point of view of neurological mediators, neurotrophins may play key roles [ 63 – 66 ]. Neurotrophins are active not only on nerve cells but also play a key role as endocrine and paracrine regulators of the cardiovascular, immune and endocrine systems to regulate homeostasis in physiological and/or pathological conditions [ 66 – 68 ].…”

“…From the point of view of neurological mediators, neurotrophins may play key roles [ 63 – 66 ]. Neurotrophins are active not only on nerve cells but also play a key role as endocrine and paracrine regulators of the cardiovascular, immune and endocrine systems to regulate homeostasis in physiological and/or pathological conditions [ 66 – 68 ]. Indeed, the brain-derived neurotrophic factor (BDNF) is normally affected under stress conditions [ 69 , 70 ] slightly increased in the serum of individuals with GD compared to the control group, even if in this study, patients with depressive diseases were not excluded which could be the underlying reason for the rise of BDNF [ 71 ].…”

Clinical Management and Therapy of Precocious Puberty in the Sapienza University Pediatrics Hospital of Rome, Italy

“…Girls who start treatment before the age of 6 have better outcomes than patients who start treatment between 6 and 8 years while starting therapy after 8 years of age does not appear to be associated with an increase in height in adulthood [1,11,71]. GnRHa therapy is generally well tolerated in childhood, although the most frequently described adverse events are headache, injection site reactions and hot flushes, which in most cases occur early and are resolved by subsequent GnRHa administrations [11,[78][79][80]. More rare is the occurrence of vaginal discharge, or the development of a sterile abscess at the injection site or at the subcutaneous implant site, which may lead to loss of efficacy of the therapy [3,76].…”

Black Chokeberry (Aronia melanocarpa) Juice Supplementation Improves Oxidative Stress and Aging Markers in Testis of Aged Rats

“…The function of neurotrophins is to maintain the survival and differentiation of neurons, but it has also been demonstrated that all known neurotrophins and their receptors are expressed in the testes [25]. In animals, three members of the tyrosine protein kinase receptor (TRK) family are known: TRK-A, which binds to the nerve growth factor (NGF); TRK-B, which binds to the brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4); and TRK-C, which binds to neurotrophin-3 (NT3) [26].…”