Therefore, it is possible that EDS may exert direct effects on both LCs and the seminiferous tubule. Alternatively, the effects on the LCs may represent indirect action resulting from direct seminiferous tubule toxicity. Finally, the effects on the seminiferous tubules may represent an indirect action resulting from direct LC toxicity. Regardless, it is now clear that prenatal exposure to EDS results in reduced fetal T and persistent alterations in LC development. Whether the permanent alterations in the seminiferous tubule, i.e., spermatogenesis, manifest from the reduced fetal T peak, are independent of the LC, or the result of alterations in LC paracrine function remains unknown. Preliminary results (G. Klinefelter, unpublished) of a proteomic evaluation of PND 1 testes from control and EDS-exposed males reveal that three proteins potentially implicated in LC steroidogenesis are diminished by gestational exposure to EDS: apolipoprotein A-1, phosphatidylethanolamine, and thioredoxin-like protein.
Future efforts will be made to follow proteomic changes at subsequent time points (i.e., PND 7 and 14) to determine whether and when putative paracrine changes might occur. Moreover, it will be important to compare changes in protein expression between isolated (i.e., laser capture and/or in vitro purification methods) fetal and progenitor LCs to changes that are observed in whole testis parenchyma.
In summary, male mice exposed to EDS from GD 1117 manifest a significant reduction in the fetal T peak, body weight-independent decreases in testis and epididymal weights, decreased epididymal sperm reserves, altered steroidogenic potential of LC, incomplete spermatogenesis, and deficits in mating and fertility. Given that LCs are fewer and smaller in the testis of EDS-exposed males, the gestational EDS exposure clearly led to a permanent lesion in the development of the LC and spermatogenesis.