Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo

Abstract

Male exposure to cigarette smoke is associated with seminal defects and with congenital anomalies and childhood cancers in offspring. In mice, paternal exposure to cigarette smoke condensate (CSC) causes molecular defects in germ cells and phenotypic effects in their offspring. Here we used an testicular explant model and exposure to determine the concentration at which CSC impairs spermatogenesis and offspring development. We explanted testis tissue at postnatal day (P)5.5 and cultured it until P11.5. Assessment of growth parameters by analyzing expression of cell-specific markers revealed that the explant system maintained structural and functional integrity. We exposed the P5.5 to -11.5 explants to various concentrations (40-160 µg/ml) of CSC and confirmed that nicotine in the CSC was metabolized to cotinine. We assessed various growth and differentiation parameters, as well as testosterone production, and observed that many spermatogenesis features were impaired at 160 µg/ml CSC. The same parameters were impaired by a similar CSC concentration Finally, females mated to males that were exposed to 160 µg/ml CSC neonatally had increased rates of pup resorption. We conclude that male exposure to CSC impairs offspring development and that the concentration at which CSC impairs spermatogenesis is similar and Given that the concentrations of CSC we used contained similar doses of nicotine as human smokers are exposed to, we argue that our model mimics human male reproductive effects of smoking.-Esakky, P., Hansen, D. A., Drury, A. M., Felder, P., Cusumano, A., Moley, K. H. Testicular cells exhibit similar molecular responses to cigarette smoke condensate and .

Paternal Exposure to Cigarette Smoke alters Behavior and Gene and miRNA Expression in Offspring

“…To determine whether paternal exposure to CSC affects growth of offspring, we used our mouse model (Esakky et al 2018) in which we intraperitoneally delivered 100 mg of CSC (or vehicle) per day to adult male mice for 40 days, which encompasses one full cycle of spermatogenesis. This treatment had no effect on the males' body weights (Fig.…”

Dysregulation of the miR-30a/BiP axis by cigarette smoking accelerates oral cancer progression

“…When the tumors reached a volume of 100 mm 3 , the mice were randomly divided into vehicle control and treatment groups (n = 5 per group). CSC (20 mg/kg body weight) or PBS (vehicle control) was administered intraperitoneally every other day for 3 weeks as previously described [ 42 , 43 ]. Tumor growth was monitored once a week using Vernier calipers, and the tumor volume was calculated according to the formula: V = (width 2 × length)/2.…”

Downregulation of Sostdc1 in Testicular Sertoli Cells is Prerequisite for Onset of Robust Spermatogenesis at Puberty

“…The streptavidin-horseradish peroxidase and diaminobenzidine tetra hydrochloride system was used to visualize for the apoptotic cells under light microscope. The number of TUNEL-positive cells per total number of seminiferous tubules within each testis cross-section was counted to determine the incidence of apoptosis in the WT and Tg testes as described previously 49–51 . A total of three cross sections per animal was analyzed for TUNEL assay at a total magnification of 20X.…”