Effects of IGF-1 on the Three-Dimensional Culture of Ovarian Preantral Follicles and Superovulation Rates in Mice

Abstract

Insulin-like growth factor-1 (IGF-1) plays a crucial role during folliculogenesis, which has been demonstrated by previous research. However, the optimal IGF-1 dosage in the three-dimensional (3D) culture system is unknown. Mouse secondary follicles (140–150 µm) were cultured for 6 days within an alginate bead in a medium supplemented with 0 (G0), 5 ng/mL (G5), 10 ng/mL (G10), or 50 ng/mL IGF-1 (G50). Secretions of 17β-estradiol and progesterone were significantly increased in G10 and G50 (p < 0.05). However, G50 significantly inhibited follicular growth (p < 0.05), while G10 showed a higher oocyte maturation rate. Thus, the 10 ng/mL IGF-1 was used in subsequent experiments. IGF-1 enhanced the function of granulosa cells (GCs) by upregulating expressions of Star, Cyp19a1, Hsd3b1, Fshr, and Lhcgr. Oocyte secretory function was promoted by upregulating expressions of Bmp-15, Gdf-9, and Fgf-8. Addition of IGF-1 showed anti-apoptotic effect. However, G10 did not improve fertilization rate of MII oocytes compared to G0. In an intraperitoneal injection experiment in mice, IGF-1 significantly increased the number of ovulated oocytes (p < 0.05). In conclusion, 10 ng/mL IGF-1 can promote the production of mature oocytes in the 3D culture medium and injection of IGF-1 before superovulation increases the number of ovulated oocytes.

Polymorphisms within the <em>IGF1</em> and <em>IGF1R</em> genes associated with superovulation-related traits in Holstein dairy cows managed in a semiarid environment

“…IGF1 acting through its receptor IGF1R has a synergistic effect with follicle-stimulating hormone (FSH) to regulate ovarian synthesis of progesterone, aromatase, estradiol, LHR, and inhibin, which are crucial hormones in the ovulatory process (Baumgarten et al 2017). IGF1 plays a critical role in both the ovarian response and embryo production in cows subjected to SPO by participating in follicular growth, oocyte competence acquisition, oocyte secretion of hormones and growth factors, synthesis of gonadotropin receptors, and embryo development and viability (Velazquez et al 2009;Dai et al 2022).…”

A PCOS Paradox: Does Inositol Therapy Find a Rationale in All the Different Phenotypes?

“…Recently, an in vitro study revealed that the stimulation of 3D follicles from mouse models with insulin-like growth factor-1 (IGF-1) causes the arrest of follicle growth when excessive IGF-1 amounts were used [ 17 ]. The authors investigated the effect of three different concentrations of IGF-1 and observed that the treatment with the highest concentration inhibited follicle growth.…”

Androgen excess: a hallmark of polycystic ovary syndrome

“…Decreased endometrial Glut4 gene expression is also regulated by ARs through binding to the GLUT promoter in rat models ( 15 ). Interestingly, one three-dimensional culture of mouse follicles in vitro demonstrated that high concentrations of insulin-like growth factor-1 (IGF-1) could inhibit mouse follicular development and maturation, which provides a possible explanation for the involvement of IGF-1 in the pathogenesis of ovulatory disorders in phenotype D in the absence of HA ( 2 , 16 ). Moreover, enhanced CYP17 activity in TCs is regulated by the PI3K/AKT pathway ( 17 ).…”