CNC-exposed paternal reproductive toxicity affects the placenta.

Details

• Personal Author:
  Campagnolo L ; Kagan VE ; Kisin ER ; Pietroiusti A ; Shrivastava I ; Shvedova AA ; Somma G ; Yanamala N
• Description:
  Exposure of mice to nanocellulose crystals (CNC) is known to affect male reproductivity caused by alterations in sperm properties such as concentration, motility, morphology and DNA integrity. Mechanisms driving these malfunctioning reproductive responses to CNC exposure are unclear. Published results support the idea that epigenetic changes contributing to male infertility have the potential for transgenerational transfer. We explored if epigenetic changes in testis affect both male reproductive function and gene/protein expression in placental tissue of unexposed females impregnated by CNC exposed males. A group of C57/ BL6J male mice was sub-chronically exposed to CNC (40ug/mouse/twice a week/3 weeks) by pharyngeal aspiration; the control group was exposed to the vehicle (USP grade water). Three months post exposure, mice were mated with naïve females and the testis and placenta tissues (exposed and control) were evaluated for gene-expression data. The CNC-exposed mice showed a significant difference in sperm cell counts, motility and immotile spermatozoa compared to non-exposed control mice. Post-weaning, 8 pups from CNC-exposed fathers died, while no death was observed in the litters from unexposed fathers, suggesting a higher fragility of pups from the CNC-exposed fathers. Differentially expressed genes (DEGs) that overlap between exposed testis and placenta of mice plugged by the exposed males was identified, resulting in a gene-set of 63 DEGs. Hierarchical clustering identified EIF3A, FXR1, LUZP1 in testis and EIF3A, TGFBR3 in placenta as significantly upregulated. The top enriched pathways and network using IPA for the same gene-set was PTEN-Signaling and Organismal Injury and Abnormalities, respectively. In conclusion, our data support the hypothesis that paternal exposure to CNC reflects adverse effects on the progeny, probably via placental mediated pathways. Disclaimer: The findings and conclusions of this report are those of the authors and do not necessarily represent the official position of National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention. [Description provided by NIOSH]
• Subjects:
  Animals Environmental Exposure Genetics Laboratories Occupational Health Risk Assessment Risk Factors Safety Urogenital System
• Keywords:
  Exposure levels; Risk factors; Animals; Laboratory animals; Reproductive effects; Genes; Proteins; Health effects
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  New Jersey ; OSHA Region 2 ; OSHA Region 3 ; Pennsylvania ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  186
• NIOSHTIC Number:
  nn:20064943
• Citation:
  Toxicologist 2022 Mar; 186(S1):220
• Federal Fiscal Year:
  2022
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 61st Annual Meeting & ToxExpo, March 27-31, 2022, San Diego, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d2bc17b8e58dad1f48f79b169921c27bbc026d32dd7a16a8a353602ecb1ee0beb7f5298bb7352fefe217fafd8590d45bb17cd0224131bf7659fccb5e3a76e812
• Download URL:
  https://stacks.cdc.gov/view/cdc/248766/cdc_248766_DS1.pdf
• File Type:
  [PDF - 240.55 KB ]