A cAMP-specific phosphodiesterase, phosphodiesterase 8B (PDE8B), affects Sertoli cell proliferation in adult mice

Monday, September 22, 2014 — Poster Session II
4:00 p.m. – 6:00 p.m.	FAES Academic Center	NICHD	MOLBIO-20

* FARE Award Winner

Authors

• E Szarek
• L Ferro Leal
• M Kotula-Balak
• B Bilinska
• CA Stratakis

Abstract

PDE8B, a cAMP-specific PDE, is highly expressed in testis.Genetic aberrations in cAMP-signaling predispose to endocrine tumors and fertility. Testes isolated from wild-type(WT) and Pde8b-/-(knock-out(KO)) mice at 6,9, and 12months(n=3-8/group).Pde8b-/- testis revealed regressive changes in seminiferous tubules(ST),containing increased atrophied tubules, 12 months (WT:0±0.001%vs.KO:11±0.012%),ST diameter significantly decreased(WT: 209.3±6.65um vs. KO: 169.6±4.22um). Atrophied tubules resembled Sertoli-cell only(SCO) syndrome. Sox9-immunostaining: significantly higher numbers of Sertoli cells(SC) in Pde8b-/-testes(KO:27.68±0.15vs.WT:19.20±0.05_Sox9+cells/tubule);SC in Pde8b-/- testes are maintained in immature state.Since spermatogonial differentiation/accumulation of spermatogonia in ST has been shown to induce germ cell death, hypothesized that germ-cell loss resulted from increased apoptosis due to accumulation of spermatogonia undergoing defective spermatogenesis.TUNEL to assess cell death revealed significantly higher numbers in Pde8b-/- testes(6mo:WT4±1.0vsKO30±8.2 cells/tubules; 12mo:WT9±1.9vsKO64±5.4 cells/tubules).Examination of junctional proteins, Cx43 and N-Cadherin, revealed failure to establish junctional characteristics of blood testis barrier,likelihood substantiated by abnormal localization of germ cells.Evaluation of blood biochemistry revealed significant increase in LDH, Pde8b-/- mice(KO:265.5±81.33vsWT:182.50±7.50U/L;P<0.05);LDH is known to be elevated in non-seminomatous germ cell tumors.Serum estradiol was elevated, but no difference in serum testosterone. Conclusion: PDE8B has a previously unknown role in SC function and proliferation;its wider role in fertility remains poorly characterized.PDE8B may be a therapeutic target for male infertility,especially that related to SC dysfunction.

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