Towards a physiological role for cytochrome P450 aromatase in ejaculated human sperm

• Published in: Human reproduction (Oxford) 2003-08, Vol.18 (8), p.1650-1659
• Main Authors: Aquila, Saveria, Sisci, Diego, Gentile, Mariaelena, Carpino, Amalia, Middea, Emilia, Catalano, Stefania, Rago, Vittoria, Andò, Sebastiano
• Format: Article
• Language: English
• Subjects: Acrosin - metabolism; Acrosome Reaction - physiology; Aromatase - genetics; Aromatase - physiology; Base Sequence; Biological and medical sciences; DNA, Complementary - genetics; Ejaculation; Estradiol - pharmacology; Estradiol - physiology; Fundamental and applied biological sciences. Psychology; Hormone metabolism and regulation; Humans; In Vitro Techniques; Key words: acrosome reaction/aromatizable androgens/cytochrome P450 aromatase/ejaculated sperm/estrogen; Male; Mammalian male genital system; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sperm Capacitation - physiology; Sperm Motility - drug effects; Sperm Motility - physiology; Spermatozoa - enzymology; Staining and Labeling; Substrate Specificity; Vertebrates: reproduction
• ISSN: 0268-1161; 1460-2350; 1460-2350
• DOI: 10.1093/humrep/deg340

BACKGROUND: Advances in the definition of the function and the mechanism of estrogen action in different tissues have come from human and animal models of estrogen insufficiency. Recently we have demonstrated that aromatase is present and biologically active in human ejaculated sperm, suggesting that autonomous estradiol sperm production may influence sperm functions. In the present study we investigate a possible physiological role for enzymatically active P450 aromatase in human ejaculated sperm. METHODS AND RESULTS: To confirm the presence of mRNA coding for P450 aromatase, total RNA isolated from human sperm underwent RT–PCR and then Southern blot analysis. In non‐capacitating medium, we observed that only estradiol and aromatizable steroids were able to increase sperm motility/migration; concomitantly they enhanced protein tyrosine phosphorylation and increased p‐44/42 extracellular signal‐regulated kinase activity. When we tested acrosin activity, it emerged that estradiol and aromatizable androgens were also able to induce the acrosome reaction evaluated by two different cytological staining techniques (triple‐stain and fluorescein isothiocyanate–Pisum sativum agglutinin). All these events were enhanced by the 2′‐O‐dibutyryladenosine‐3′,5′‐cyclic monophosphate and inhibited in the presence of the specific aromatase inhibitor, letrozole. CONCLUSIONS: From this study, it appears that a link exists between the locally produced estradiol (from ejaculated sperm), sperm capacitation and the acrosome reaction. The induction of both events by aromatizable androgens in the absence of exogenous mediators suggests that estrogen biosynthesis in ejaculated sperm is a process that may influence the intrinsic sperm fertilizing capability.