Several lines of evidence suggest that insulin-like growth factor 1 (IGF1) is involved in Sertoli cell (SC) proliferation and that its receptor (IGF1R) could mediate follicle-stimulating hormone (FSH) effects. To examine the role of the growth hormone (GH)-IGF1 axis on SC function, we evaluated the effects of GH and IGF1 on basal and FSH-modulated SC proliferation, as well as on anti-Müllerian hormone (AMH) and inhibin B expression and secretion in-vitro. SCs from neonatal pigs were incubated with (1) placebo, (2) 100 nM highly purified urofollitropin (hpFSH), (3) 100 nM recombinant GH (rGH), (4) 100 nM recombinant IGF1 (rIGF1), (5) 100 nM hpFSH plus 100 nM rGH, (6) 100 nM hpFSH plus 100 nM rIGF1, for 48 h. We found that IGF1, but not FSH nor GH, stimulated SC proliferation. Furthermore, an inhibitory effect of FSH, GH and IGF1 on AMH secretion, and a stimulatory role of FSH and IGF1, but not GH, on inhibin B secretion were found. These results suggest that the GH-IGF1 axis influences basal and FSH-modulated SC proliferation and function. We speculate that SC proliferation occurring in childhood might be supported by the increased serum IGF1 levels observed during this period of life.

Experimental evidence has shown that the IGF1 receptor (IGF1R) is involved in testicular development during embryogenesis. More recently, data gathered from mice granulosa cells and zebrafish spermatogonia suggest that IGF1R has a role in Follicle-stimulating hormone (FSH) signaling. No evidence has been reported on this matter in Sertoli cells (SCs) so far. The aim of the study was to evaluate the role, if any, of the IGF1R in FSH signaling in SCs. The effects of FSH exposure on myosin-phosphatase 1 (MYPT1), ERK 1/2, AKT308, AKT473, c-Jun N-terminal kinase (JNK) phosphorylation and on anti-Müllerian hormone (AMH), inhibin B and FSH receptor (FSHR) mRNA levels were assessed with and without the IGF1R inhibitor NVP-AEW541 in purified and functional porcine neonatal SCs. Pre-treatment with NVP-AEW541 inhibited the FSH-induced MYPT1 and ERK 1/2 phosphorylation, decreased the FSH-dependent Protein kinase B (AKT)308 phosphorylation, but did not affect the FSH-induced AKT473 and JNK phosphorylation rate. It also interfered with the FSH-induced AMH and FSHR down-regulation. No influence was observed on the FSH-stimulated Inhibin B gene expression. Conclusion. These findings support the role of theIGF1R in FSH signaling in porcine SCs. The possible influence of IGF1 stimulation on the FSH-mediated effects on SCs should be further explored.

There is ongoing debate as to whether the decline of sperm production in recent times may be related to a parallel increase in the rate of obesity and diabetes. Lower anti-Müllerian hormone (AMH) and inhibin B secretion have been observed in young hyperinsulinemic patients compared to healthy controls, suggesting a Sertoli cell (SC) dysfunction. The pathophysiological mechanisms underlying SC dysfunction in these patients are poorly understood. To the best of our knowledge, no evidence is available on the effects of insulin on SC function. Therefore, this study was undertaken to assess the effects of insulin on basal and follicle-stimulating hormone (FSH)-stimulated SC function in vitro. To accomplish this, we evaluated the expression of AMH, inhibin B and FSHR genes, the secretion of AMH and inhibin B and the phosphorylation of AKT473 and SC proliferation on neonatal porcine SC after incubation with FSH and/or insulin. We found that similar to FSH, the expression and secretion of AMH is suppressed by insulin. Co-incubation with FSH and insulin decreased AMH secretion significantly more than with FSH alone. Insulin had no effect on the expression and secretion of the inhibin B gene, but co-incubation with FSH and insulin had a lower effect on inhibin B secretion than that found with FSH alone. FSH and/or insulin increased AKT473 phosphorylation and SC proliferation. In conclusion, the results of this study showed that insulin modulates SC function. We hypothesize that hyperinsulinemia may therefore influence testicular function even before puberty begins. Therefore, particular care should be taken to avoid the onset of hyperinsulinemia in children to prevent a future deleterious effect on fertility.

To evaluate whether the follicle-stimulating hormone (FSH) receptor (FSHR) is expressed in human spermatozoa and the effects of FSH incubation on sperm function. Twenty-four Caucasian men were recruited. Thirteen patients had asthenozoospermia, and the remaining 11 had normal sperm parameters (controls). After confirming FSHR expression, spermatozoa from patients and controls were incubated with increasing concentrations of human purified FSH (hpFSH) to reassess FSHR expression and localization and to evaluate progressive and total sperm motility, the mitochondrial membrane potential, and protein kinase B (AKT) 473 and 308 phosphorylation. FSHR is expressed in the post-acrosomal segment, neck, midpiece, and tail of human spermatozoa. Its localization does not differ between patients and controls. Incubation with hpFSH at a concentration of 30 mIU/mL appeared to increase FSHR expression mainly in patients. Incubation of human spermatozoa with hpFSH overall resulted in an overall deterioration of both progressive and total motility in patients and controls and worse mitochondrial function only in controls. Finally, incubation with FSH increased AKT⁴⁷³/tubulin phosphorylation to a greater extent than AKT³⁰⁸. FSHR is expressed in the post-acrosomal region, neck, midpiece, and tail of human spermatozoa. Contrary to a previous study, we report a negative effect of FSH on sperm motility and mitochondrial function. FSH also activates the AKT⁴⁷³ signaling pathway.

This study aimed to evaluate the intrinsic in vitro performance of naïve porcine prepubertal Sertoli cells (SCs) and SCs loaded with blank poly(lactic acid) microparticles (MP) or amphotericin B poly(lactic acid) microparticles (AmB-MP) against Candida tropicalis, a prevalent pathogenic non-albicans species. The objective was to assess their impact on biofilm formation and the cellular response mechanisms involved, building on previous findings that highlight SCs’ potential as anti-infective agents and drug carriers. Our results demonstrated that SCs successfully internalized Candida tropicalis while maintaining viability and exhibited a strong anti-infective effect, inhibiting biofilm formation by 70%. This inhibition increased to 80–90% when SCs were combined with AmB-MP. The interaction between SCs (both naïve and MP-loaded) and Candida tropicalis triggered the activation of MAPK, AKT, and NF-kB signaling pathways, leading to the upregulated expression of innate immune factors such as MHC-II, TLR-4, TGF-β, IDO, and β-defensin 123. These findings reinforce the role of SCs in infection control and drug delivery. Furthermore, their anti-infective and scavenging activity is linked to a tolerogenic phenotype, suggesting a potential dual therapeutic role at the host–pathogen interface.

Moringa oleifera is widely recognized for its pharmacological properties and has recently attracted interest for its potential anticancer effects. In this study, we investigated the in vitro activity of Moringa oleifera leaf extract on the human prostate cancer PC3 cell line, focusing on the insulin-like growth factor 1 receptor (IGF1R) signaling pathway, a central regulator of prostate cancer progression. PC3 cells were treated with Moringa oleifera extract, IGF-1, the IGF1R inhibitor NVP-AEW541, and their combinations. Cell migration, apoptosis, cell cycle distribution, gene expression, and protein regulation were evaluated using scratch assays, flow cytometry, RT-PCR, and Western blotting. Under our experimental conditions, Moringa oleifera extract was associated with reduced IGF1R expression and phosphorylation, together with decreased activation of downstream ERK/MAPK and AKT signaling pathways. These changes were accompanied by increased apoptosis, G0/G1 cell cycle accumulation, and reduced migratory capacity of PC3 cells. In addition, Moringa oleifera modulated the expression of genes involved in epithelial–mesenchymal transition, tumor progression, and extracellular matrix remodeling, suppressing pro-invasive markers while enhancing anti-metastatic factors. The extract also reduced the expression of bone metastasis–associated markers, including osteocalcin and alkaline phosphatase. Overall, these findings indicate that Moringa oleifera exposure is associated with modulation of IGF1R-related signaling and cellular programs relevant to aggressive prostate cancer. Further studies will be required to determine pharmacological feasibility and translational relevance.