Voltage-dependent anion channels are a key factor of male fertility

• Published in: Fertility and sterility Vol. 99; no. 2; pp. 354 - 361
• Main Authors: Kwon, Woo-Sung, B.S, Park, Yoo-Jin, M.S, Mohamed, El-Sayed A., Ph.D, Pang, Myung-Geol, Ph.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2013
• Subjects: Acrosome - metabolism; acrosome reaction; Animals; calcium; DIDS; embryogenesis; Female; fluorescence; fluorescent antibody technique; human chorionic gonadotropin; in vitro fertilization; Infertility, Male - metabolism; Internal Medicine; Male; male fertility; Mice; Mice, Inbred ICR; Mitochondrial Membrane Transport Proteins - metabolism; Obstetrics and Gynecology; oocytes; phosphorylation; pregnant mare serum gonadotropin; prospective studies; Sperm Capacitation; sperm function; spermatozoa; tyrosine; VDAC; viability; Voltage-Dependent Anion Channel 2 - metabolism; Voltage-Dependent Anion Channels - metabolism; Western blotting; VDAC; sperm function; male fertility; DIDS
• ISSN: 0015-0282; 1556-5653
• DOI: 10.1016/j.fertnstert.2012.09.021

Objective To examine how voltage-dependent anion channels (VDACs) regulate sperm function in capacitation conditions. Design Experimental prospective study. Setting Academic research laboratory. Animal(s) Male ICR and female B6D2F1/CrljOri mice (8–12 weeks old). Intervention(s) Female mice were superovulated with 5 IU of pregnant mare serum gonadotropin given IP and 5 IU of hCG given IP 48 hours later. Oocytes were applied to assess fertilization and embryo development. Main Outcome Measure(s) Immunofluorescence assay, computer-assisted sperm analysis, hypo-osmotic swelling test, combined Hoechst 33258/chlortetracycline fluorescence assessment of capacitation status, measurement of [Ca2+ ]i and [pH]i , Western blotting, and IVF. Result(s) VDAC2 was localized on the acrosomal region and principal piece, while VDAC3 was localized on the acrosomal region and midpiece. Blocking VDAC with DIDS (500 μM) significantly decreased motility, viability, acrosome reaction, capacitation, tyrosine phosphorylation, fertilization, and embryo development regardless of Ca2+ . However, the most severe decreases were observed in the presence (+) of DIDS and absence (−) of Ca2+ , respectively. A significant decrease in [Ca2+ ]i concentration was observed in (−) DIDS, while [pH]i was significantly increased in (−) DIDS regardless of Ca2+ . However, a significantly elevated [pH]i was observed in (+) Ca2+. Conclusion(s) Abnormal regulation of VDACs negatively affected sperm function. Thus, VDACs may be key regulators of the fertilization ability of spermatozoa.