This study addresses the role of cAMP hydrolytic isoenzyme phosphodiesterase type 3 (PDE 3) modulation on human oocyte maturation in vitro. Presence of phosphodiesterase type 3 A (PDE 3A) mRNA was confirmed in human germinal vesicle-stage (GV) oocytes. Making use of a selective PDE 3 inhibitor, Org 9935 (10 microM), oocytes retrieved from immature follicles were arrested in prophase I with a high efficiency for up to 72 h. Cumulus oocyte complexes (COCs) were retrieved in the follicular phase of the cycle before or after exposure to endogenous LH or hCG administration in vivo and randomly distributed into maturation medium with or without the PDE 3 inhibitor. Previous exposure of small follicles to LH activity in vivo had no influence on the arresting capacity of the PDE 3 inhibitor. Reversal from pharmacological arrest leads to a progression through meiosis in a normal time frame with formation of a well-aligned metaphase plate. Ultrastructure analysis of COC derived from follicles between 8 and 12 mm showed that the induced extension of prophase I arrest in vitro resulted in cytoplasm changes but not in apparent nuclear changes during culture.
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http://dx.doi.org/10.1095/biolreprod.103.015982 | DOI Listing |
Basic Clin Androl
January 2025
Chair of Endocrinology and Medical Sexology (ENDOSEX), Dept. of Systems Medicine, University of Rome Tor Vergata, via Montpellier 1, Rome, 00133, Italy.
The serendipitous discovery that inhibiting type 5 phosphodiesterase (PDE5) using sildenafil, a potent PDE5 inhibitor (PDE5i) initially developed for cardioprotection, introduced the possibility of orally managing erectile dysfunction (ED) led to an increase in research data, which are currently considered groundbreaking for the new discipline of sexual medicine. Findings from a number of laboratories and clinics around the world unanimously demonstrated the following: (i) the major cause of ED is directly or indirectly related to cardiovascular disease (CVD); (ii) ED and CVDs share the same risk factors, which are related mainly to lifestyle choices; (iii) the first therapeutic approach to both ED and CVDs is to transform harmful lifestyles into virtuous lifestyles; and (iv) PDE5is in general, particularly sildenafil, are very safe, if not protective, for use in CVD patients. However, the use of PDE5is has faced several challenges.
View Article and Find Full Text PDFJ Cereb Blood Flow Metab
January 2025
Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Pontypridd, UK.
To what extent sildenafil, a selective inhibitor of the type-5 phosphodiesterase modulates systemic redox status and cerebrovascular function during acute exposure to hypoxia remains unknown. To address this, 12 healthy males (aged 24 ± 3 y) participated in a randomized, placebo-controlled crossover study involving exposure to both normoxia and acute (60 min) hypoxia (Fi = 0.14), followed by oral administration of 50 mg sildenafil and placebo (double-blinded).
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
January 2025
Division of Molecular Psychiatry, Center of Mental Health, University of Hospital Würzburg, 97080 Würzburg, Germany.
Background: The inheritance of the short allele, encoding the serotonin transporter (SERT) in humans, increases susceptibility to neuropsychiatric and metabolic disorders, with aging and female sex further exacerbating these conditions. Both central and peripheral mechanisms of the compromised serotonin (5-HT) system play crucial roles in this context. Previous studies on SERT-deficient (Sert) mice, which model human SERT deficiency, have demonstrated emotional and metabolic disturbances, exacerbated by exposure to a high-fat Western diet (WD).
View Article and Find Full Text PDFMetab Brain Dis
January 2025
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Hale Building for Transformative Medicine, Room 10006, 60 Fenwood Road, Boston, MA, 02115, USA.
α-Synuclein (αS) is a 140 amino-acid neuronal protein highly enriched in presynaptic nerve terminals. Its progressive accumulation in Lewy bodies and neurites is the hallmark of Parkinson's disease (PD). A growing number of studies highlights a critical interplay between lipid metabolism and αS biology.
View Article and Find Full Text PDFCells
January 2025
Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece.
Phosphodiesterases, particularly the type 5 isoform (PDE5), have gained recognition as pivotal regulators of male reproductive physiology, exerting significant influence on testicular function, sperm maturation, and overall fertility potential. Over the past several decades, investigations have expanded beyond the original therapeutic intent of PDE5 inhibitors for erectile dysfunction, exploring their broader reproductive implications. This narrative review integrates current evidence from in vitro studies, animal models, and clinical research to clarify the roles of PDEs in effecting the male reproductive tract, with an emphasis on the mechanistic pathways underlying cyclic nucleotide signaling, the cellular specificity of PDE isoform expression, and the effects of PDE5 inhibitors on Leydig and Sertoli cell functions.
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