Group IVA phospholipase A2 regulates testosterone biosynthesis by murine Leydig cells and is required for timely sexual maturation

Abstract

In the present paper, we report that PLA2G4A (Group IVA phospholipase A2) is important in the development and function of rodent testes. Interstitial cells of rat testes had high PLA2 (phospholipase A2) activity that was very sensitive to the PLA2G4A-preferential inhibitor AACOCF3 (arachidonyl trifluoromethyl ketone). PLA2G4A protein was expressed primarily in the interstitial cells of wild-type mouse testes throughout maturation. Although Pla2g4a knockout (Pla2g4a−/− ) male mice are fertile, their sexual maturation was delayed, as indicated by cauda epididymal sperm count and seminal vesicle development. Delayed function of Pla2g4a−/− mice testes was associated with histological abnormalities including disorganized architecture, swollen appearance and fewer interstitial cells. Basal secretion of testosterone was attenuated significantly and steroidogenic response to hCG (human chorionic gonadotropin) treatment was reduced in Pla2g4a−/− mice compared with their Pla2g4a+/+ littermates during the sexual maturation period. Chemical inhibition of PLA2G4A activity by AACOCF3 or pyrrophenone significantly reduced hCG-stimulated testosterone production in cultured rat interstitial cells. AACOCF3 inhibited forskolin- and cAMP analogue-stimulated testosterone production. These results provide the first evidence that PLA2G4A plays a role in male testes physiology and development. These results may have implications for the potential clinical use of PLA2G4A inhibitors.

Genome‐wide detection of signatures of selection in Korean Hanwoo cattle

“…Another two genes that are worth noting due to their participation in testis development are PLA2G4A (Kurusu et al . ), which also is linked to the ovulation process (Diouf et al . ) and speculatively to prostaglandin F2a reproductive pathways (Ababneh & Troedsson ), and OVOL1, which interacts with ID2 , both regulators of spermatogenesis (Li et al .…”

Group IVA phospholipase A2optimizes ovulation and fertilization in rodents through induction of and metabolic coupling with prostaglandin endoperoxide synthase 2

“…C57BL/6J mice used in the present study were generated previously by gene targeting to disrupt an exon of the Pla2g4a gene that resulted in creation of a null allele (21, 32). Heterozygotes were interbred to produce homozygous null and wild‐type littermate mice.…”

“…In the superovulation model, adult female mice received a single dose of equine chorionic gonadotropin (eCG; 0.2 IU/g of body weight, intraperitoneally; Sigma Chemical Co., St. Louis, MO, USA) and 48 h later, were injected with human CG (hCG; 5 IU/mouse, intraperitoneally; Sigma). Female mice were housed overnight with a fertile male of various Pla2g4a genotypes (21, 32), and mating was confirmed by the presence of a vaginal plug the next morning [day 1 of pregnancy (PRG1)]. Between 9:00 and 11:00 AM on day 2 of pregnancy (PRG2) we sampled blood by cardiac puncture and sacrificed the mice.…”

“…Western blot analysis was performed as previously reported (30, 32). Whole ovarian tissue samples were transferred into lysis buffer (20 mM HEPES, pH7.4; 2 mM EGTA; 1 mM DTT; 1 mM NaVO 4 ; 1% Triton X‐100; 10% glycerol; 2 μM leupeptin; 400 μM PMSF; and 50 μM β‐glycerophosphate), homogenized, and stored at —80°C until processing.…”

Cytosolic phospholipase A2: physiological function and role in disease

“…A more detailed study showed that cPLA 2 ␣ modestly regulates ovulation and fertilization by promoting the induction of COX-2 for PG production ( 153 ). A role for cPLA 2 ␣ in regulating male sexual maturation has also been described ( 154 ). Male cPLA 2 ␣ KO mice are fertile but exhibit abnormal histology of the testes showing a reduced number of interstitial cells.…”