Expression of a mitochondrial progesterone receptor in human spermatozoa correlates with a progestin‐dependent increase in mitochondrial membrane potential

• Published in: Andrology (Oxford) Vol. 2; no. 6; pp. 875 - 883
• Main Authors: Tantibhedhyangkul, J., Hawkins, K. C., Dai, Q., Mu, K., Dunn, C. N., Miller, S. E., Price, T. M.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-11-2014
• Subjects: human spermatozoa; Humans; immunocytochemistry; immunoelectron microscopy; Male; Membrane Potential, Mitochondrial - drug effects; Microscopy, Fluorescence; Microscopy, Immunoelectron; Mitochondria - metabolism; mitochondrial membrane potential; mitochondrial progesterone receptor; Progestins - pharmacology; Receptors, Progesterone - metabolism; Spermatozoa - metabolism; immunocytochemistry; immunoelectron microscopy; human spermatozoa; mitochondrial progesterone receptor; mitochondrial membrane potential
• ISSN: 2047-2919; 2047-2927
• DOI: 10.1111/j.2047-2927.2014.00263.x

Summary
The hyperactivation of human spermatozoa necessary for fertilization requires a substantial increase in cellular energy production. The factors responsible for increasing cellular energy remain poorly defined. This article proposes a role for a novel mitochondrial progesterone receptor (PR‐M) in modulation of mitochondrial activity. Basic science studies demonstrate a 38 kDa protein with western blot analysis, consistent with PR‐M; whereas imaging studies with confocal and immunoelectron microscopy demonstrate a PR on the mitochondria. Treatment with a PR‐specific progestin shows increased mitochondrial membrane potential, not related to induction of an acrosome reaction. The increase in mitochondrial membrane potential was inhibited by a specific PR antagonist, but not affected by an inhibitor to the progesterone‐dependent Catsper voltage‐activated channel. In conclusion, these studies suggest expression of a novel mitochondrial PR in human spermatozoa with a progestin‐dependent increase in mitochondrial activity. This mechanism may serve to enhance cellular energy production as the spermatozoa traverse the female genital tract being exposed to increasing concentrations of progesterone.