4.3 Article

Per- and polyfluoroalkyl substances impact human spermatogenesis in a stem-cell-derived mode

期刊

SYSTEMS BIOLOGY IN REPRODUCTIVE MEDICINE
卷 64, 期 4, 页码 225-239

出版社

TAYLOR & FRANCIS INC
DOI: 10.1080/19396368.2018.1481465

关键词

Perfluorooctanesulfonic acid (PFOS); perfluorooctanoic acid (PFOA); perfluorononanoic acid (PFNA); in vitro spermatogenesis; male reproductive toxicity

资金

  1. National Science Foundation [DGE-1444932]
  2. National Institutes of Health [1K22 ES025418-01, P30 ES019776-01-A1]
  3. Emory University's Atlanta Clinical & Translational Science Institute and University Research Committee (ACTSI/URC) award
  4. NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [K22ES025418, P30ES019776] Funding Source: NIH RePORTER
  5. OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [P51OD011132] Funding Source: NIH RePORTER

向作者/读者索取更多资源

Per- and polyfluoroalkyl substances (PFASs) represent a highly ubiquitous group of synthetic chemicals used in products ranging from water and oil repellents and lubricants to firefighting foam. These substances can enter and accumulate in multiple tissue matrices in up to 100% of people assessed. Though animal models strongly identify these compounds as male reproductive toxicants, with exposed rodents experiencing declines in sperm count, alterations in hormones, and DNA damage in spermatids, among other adverse outcomes, human studies report conflicting conclusions as to the reproductive toxicity of these chemicals. Using an innovative, human stem-cell-based model of spermatogenesis, we assessed the effects of the PFASs perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and a mixture of PFOS, PFOA, and PFNA for their impacts on human spermatogenesis in vitro under conditions relevant to the general and occupationally exposed populations. Here, we show that PFOS, PFOA, PFNA, and a mixture of PFOS, PFOA, and PFNA do not decrease in vitro germ cell viability, consistent with reports from human studies. These compounds do not affect mitochondrial membrane potential or increase reactive oxygen species generation, and they do not decrease cell viability of spermatogonia, primary spermatocytes, secondary spermatocytes, or spermatids in vitro under the conditions examined. However, exposure to PFOS, PFOA, and PFNA reduces expression of markers for spermatogonia and primary spermatocytes. While not having direct effects on germ cell viability, these effects suggest the potential for long-term impacts on male fertility through the exhaustion of the spermatogonial stem cell pool and abnormalities in primary spermatocytes.

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