"In vitro" Effect of Different Follicle-Stimulating Hormone Preparations on Sertoli Cells: Toward a Personalized Treatment for Male Infertility.

Iva Arato,Giovanni Luca,Francesca Mancuso,Riccardo Calafiore,Meritxell Jodar,Domenico Milardi,Giuseppe Grande,Francesca Mancini,Rafael Oliva,Federica Vincenzoni,Catia Bellucci,Ferran Barrachina,Alfredo Pontecorvi,Cinzia Lilli,Maria Chiara Aglietti

doi:10.3389/fendo.2020.00401

Abstract

Follicle-stimulating hormone (FSH), a major regulator of spermatogenesis, has a crucial function in the development and function of the testis and it is extensively given as a fertility treatment to stimulate spermatogenesis. We analyzed the effects of different FSH preparations (α-follitropin, β-follitropin, and urofollitropin) in combination with testosterone on porcine pre-pubertal Sertoli cells. To study the effect of the different FSH treatments in the Sertoli cell function we performed Real Time PCR analysis of AMH, inhibin B, and FSH-r, an ELISA assay for AMH and inhibin B, and a high-throughput comparative proteomic analysis. We verified that all three preparations induced a reduction of AMH in terms of mRNA and secreted proteins, and an increase of inhibin B in terms of mRNA in all the FSH formulations, while solely α-follitropin produced an increase of secreted inhibin B in the culture medium. Comparative proteomic analysis of the three FSH preparations identified 46 proteins, 11 up-regulated and 2 down-regulated. Surprisingly, the combination of testosterone with β-follitropin specifically induced an up-regulation of eight specific secreted proteins. Our study, showing that the three different FSH preparations induce different effects, could offer the opportunity to shed light inside new applications to a personalized reproductive medicine.

Highlights

Follicle-stimulating hormone (FSH), a glycoprotein hormone secreted by the anterior pituitary gland, plays a key function in the treatment of human infertility
Anti-Müllerian Hormone (AMH) gene expression in Sertoli cell (SC) was significantly down-regulated by treatment with α, β-follitropin, and urofollitropin in combination with testosterone treatment compared with testosterone alone (Figure 2A, p < 0.001)
Inhibin B expression was significantly increased after treatment with α, β-follitropin, and urofollitropin, each other combined with testosterone treatment compared with testosterone alone (Figure 2A, p < 0.001)

Summary

Introduction

Follicle-stimulating hormone (FSH), a glycoprotein hormone secreted by the anterior pituitary gland, plays a key function in the treatment of human infertility. The preparations of FSH available in the market are derived by either recombinant DNA technology (rFSH such as α- and βfollitropin) or post-menopausal urines (urofollitropin). Α- and βfollitropins are synthesized by the same recombinant technology, producing identical dimeric α-FSH and β-FSH subunits, but with differences in the further glycosylation and in the procedures of purification. The low specific activity of this preparation could be explained by the fact that more than 95% of the protein content correspond to non-specific co-purified urinary proteins [1]

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