Effects of Insulin on Porcine Neonatal Sertoli Cell Responsiveness to FSH In Vitro.

Rossella Cannarella,Catia Bellucci,Cinzia Lilli,Laura M Mongioì,Iva Arato,Giovanni Luca,Aldo E Calogero,Sandro La Vignera,Francesca Mancuso,Rosita A Condorelli

doi:10.3390/jcm8060809

Rossella Cannarella, Catia Bellucci + Show 8 more

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https://doi.org/10.3390/jcm8060809

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Abstract

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.

Highlights

Sertoli cells (SCs), the only somatic constituent of the testicular seminiferous epithelium, are mainly involved in supporting spermatogenesis
As cultures of SCs from pre-pubertal porcine testes have been developed to reproduce an in vitro reliable prototype of pre-pubertal human testicular tissue [16], the purpose of this study was to evaluate the effects of insulin on both basal and follicle-stimulating hormone (FSH)-stimulated SC function in this model to better understand the rationale of the results reported in humans [13,14,15]
Compared with hpFSH stimulation, inhibin B gene expression was significantly downregulated by rInsulin (−89.4%; p < 0.0001) and a trend for lower levels was found after incubation with hpFSH plus rInsulin (−15.8%; p = 0.05)

Summary

Introduction

Sertoli cells (SCs), the only somatic constituent of the testicular seminiferous epithelium, are mainly involved in supporting spermatogenesis They provide structural support to germ cells (GCs), constitute the blood–testicular barrier, assist the movement of GCs within the seminiferous epithelium and guide the maturation of GCs through secretion products. They support a finite number of GCs [1,2]. Immature and actively proliferating SCs may be found in the testis until puberty At this stage, the testis is mainly made up of AMH-secreting SCs. The overall number of SCs is known to impact testicular volume. Concomitant with the onset of spermatogenesis, the testicular volume increases and GCs become the predominant testicular component (for review, see [3,4])

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