Inactivation of the IGF-I receptor gene in primary Sertoli cells highlights the autocrine effects of IGF-I

Abstract

IGF-I regulates pituitary and gonadal functions, and is pivotal for sexual development and fertility in mammalian species. To better understand the function of autocrine IGF-I in Sertoli cell physiology, we established a system for Cre-mediated conditional inactivation of the IGF-I receptor (IGF-IR) in cultured Sertoli cells. We show here that loss of IGF-IR decreased the number of viable Sertoli cells as a consequence of diminished Sertoli cell proliferation and increased Sertoli cell death.Furthermore, the lack of IGF-IR altered the morphology of cultured Sertoli cells and decreased lactate and transferrin secretions. Collectively, our data indicate that autocrine IGF-I contributes significantly to Sertoli cell homeostasis. The described in vitro system for loss-of-function analysis of the IGF-IR can be readily transposed to study the role of other intratesticular growth factors involved in spermatogenesis.

Differential organ phenotypes after postnatal Igf1r gene conditional deletion induced by tamoxifen in UBC-CreERT2; Igf1r fl/fl double transgenic mice

“…The testes were the most affected organ, showing a strong reduction in germ cell content and spermatogenesis progression, which would explain their growth deficit. Since similar phenotypes were previously described in mice with a conditional deletion of Igf1r in Sertoli cells, our results help emphasize the essential role of this receptor in mediating cell signaling in the aforementioned testicular cells (Froment et al 2007;Pitetti et al 2013). Histological changes were also found in liver and alveolar lung parenchyma, perceived as abundant mitotic figures in the liver and increased cell density in alveolar areas, most probably a consequence of their increased proliferation rates.…”

The role of microenvironment in testicular germ cell tumors

“…2). [45][46][47] These factors regulate testicular function at several levels. IGF-I enhances the testosterone production in Leydig cells, 45 guarantees Sertoli cell homeostasis 46 and stimulates spermatogonia proliferation.…”

“…[45][46][47] These factors regulate testicular function at several levels. IGF-I enhances the testosterone production in Leydig cells, 45 guarantees Sertoli cell homeostasis 46 and stimulates spermatogonia proliferation. 47 It has been also proven that the IGF-I is required for the appropriate migration of primordial germ cells; more precisely, IGF1R1b-deficient mice present a reduced number of germ would occur through a process known as reprogramming, which occurs through the upregulation of several genes important for maintaining anundifferentiated state (Fig.…”

The Effects of Local and Systemic Growth Hormone Treatment on Germ Cell Population and Fertility in an Experimental Unilateral Testicular Torsion and Orchiectomy Model

“…15e18,28 GH receptor has been found at all stages of Leydig cell development and it stimulates the maturation of Leydig cells. 17,19 Studies of the somatotropic axis in mutants showed that decreased stimulation due to GH can lead to delayed sexual maturation, malfunction of gonads in both genders and a decrease in fertility. 16,29 Therefore, GH may increase the function of survived germ cells as well as subsequent fertility and fecundity in an experimental testicular torsion model.…”