Files
Abstract
It is estimated that 1 in 6 adults struggle with infertility worldwide. Of these cases, nearly 50% are attributed in part to male factors, yet female factors are most often scrutinized. Over the past 50 years, global semen parameters have rapidly declined, and these abnormal changes can be linked to up to 35% of infertility cases. While these and other male factor infertility cases can be attributed to a known cause, others cannot be attributed to a causal factor. However, the literature suggests that some unknown causes may be linked to lifestyle choices and environmental exposures. One lifestyle factor particularly popular amongst men is cigarette smoking. In 2020 it was estimated that 1.18 billion people smoked tobacco with a prevalence rate of 32.6% of men globally. Cigarette smoke contains over 5000 chemicals, including toxicants and carcinogens. Studies have suggested that smoking decreases male fertility factors including semen parameters, testicular volume, reproductive hormones, and sexual function. However, there is limited knowledge of the direct impacts of smoking and its mechanism of harm on spermatogenesis and the microenvironment that supports the production of germ cells.
In these studies, we utilized 3 in vitro cell culture models to analyze the impacts of tobacco smoke extract exposure (TSE) on human spermatogenesis and the Sertoli cell blood-testis barrier (BTB). Utilizing 2 stem cell-based in vitro spermatogenesis models, we demonstrated significant alterations in reactive oxygen species for two cell lines, although the results differed among lines. We noted no change in cell viability or cell cycle for our differentiating stem cells. In the immortalized Sertoli cells and BTB model we demonstrated significant alterations to the cell cytotoxicity, damage, and apoptosis rates of TSE treated cells with significant changes in the integrity and permeability of the BTB. Interesting variations among the stem cell and Sertoli cell studies indicate significant alterations to cells exposed to TSE, however the results differ among cell lines and assays. These models provided an effective way to test the impacts of toxic exposures on spermatogenesis and the testis microenvironment. Utilizing these models, we demonstrated potential concerns for smoking on male fertility in vitro.