Unusual suspects: Glial cells in fertility regulation and their suspected role in polycystic ovary syndrome

Abstract

Gonadotropin-releasing-hormone (GnRH) neurons sitting within the hypothalamus control the production of gametes and sex steroids by the gonads, therefore ensuring survival of species. As orchestrators of reproductive function, GnRH neurons integrate information from external and internal cues. This occurs through an extensively studied neuronal network known as the "GnRH neuronal network." However, the brain is not simply composed of neurons. Evidence suggests a role for glial cells in controlling GnRH neuron activity, secretion and fertility outcomes, although numerous questions remain. Glial cells have historically been seen as support cells for neurons. This idea has been challenged by the discovery that some neurological diseases originate from glial dysfunction. The prevalence of infertility disorders is increasing worldwide, with one in four couples being affected; therefore, it remains essential to understand the mechanisms by which the brain controls fertility. The "GnRH glial network" could be a major player in infertility disorders and represent a potential therapeutic target. In polycystic ovary syndrome (PCOS), the most common infertility disorder of reproductive aged women worldwide, the brain is considered a prime suspect. Recent studies have demonstrated pathological neuronal wiring of the "GnRH neuronal network" in PCOS-like animal models. However, the role of the "GnRH glial network" remains to be elucidated. In this review, I aim to propose glial cells as unusual suspects in infertility disorders such as PCOS. In the first part, I state our current knowledge about the role of glia in the regulation of GnRH neurons and fertility.In the second part, based on our recent findings, I discuss how glial cells could be implicated in PCOS pathology.

SEMA6A drives GnRH neuron-dependent puberty onset by tuning median eminence vascular permeability

“…5a). To identify the source of SEMA6A in the ME, additional staining with markers for different cell types (secretory neurons, astrocytes, β-tanycytes and oligodendrocytes (OLs)) involved in ME homeostasis were performed 43,44 . SEMA6A was not detected in the Synaptophysin + terminals of neurosecretory neurons (Fig.…”

“…4). These cells are known to play key roles in GnRH neuron plasticity 43,44 . Instead, we identified maturing OLs as the source of SEMA6A in the ME (Fig.…”

Investigation of the Effects of Metallic Nanoparticles on Fertility Outcomes and Endocrine Modification of the Hypothalamic-Pituitary-Gonadal Axis

“…The results presented herein were obtained using T98G cells, a multiformal human glioblastoma and not in neurons that could secrete GnRH. It should be noted that GnRH neurons do not express the male and female steroid hormone receptors needed for the feedback regulation of the HPGA (Figure 2) [25]. Thus, the action of other cells in HPGA regulation is needed.…”

“…These other cells are glial cells, as we used in our previous experiments [17][18][19]. Indeed, these cells have been suspected of causing infertility disorders, such as polycystic ovary syndrome [25]. It is suggested that glia is able to release soluble factors as transforming factors and neurorregulins, which may affect neurons and other glial cells for regulating the GnRH pathway [26].…”