Prenatal nicotine exposure induces thymic hypoplasia in mice offspring from neonatal to adulthood

Toxicol Lett. 2019 Apr:304:30-38. doi: 10.1016/j.toxlet.2018.12.015. Epub 2018 Dec 31.

Abstract

Clinical study showed that smoking during pregnancy deceased the thymus size in newborns. However, the long-term effect remains unclear. This study was aimed to observe the effects of prenatal nicotine exposure (PNE) on the development of thymus and the T-lymphocyte subpopulation in mice offspring from the neonatal to adulthood. Both the thymus weight and cytometry data indicated that PNE caused persistent thymic hypoplasia in male offspring from neonatal to adult period and transient changes in female offspring from neonatal to prepuberal period. Flow cytometry analysis disclosed a permanent decreased proportion and number of mature CD4 single-positive (SP) T cells in thymus of both sex. In addition, the PNE male offspring showed a more serious thymus atrophy in the ovalbumin (OVA)-sensitized model. Moreover, increased autophagic vacuole and elevated mRNA expression of Beclin 1 were noted in PNE fetal thymus. In conclusion, PNE offspring showed thymus atrophy and CD 4 SP T cell reduction at different life stages. Mechanically, PNE induced excessive autophagy in fetal thymocytes might be involved in these changes. All the results provided evidence for elucidating the PNE-induced programmed immune diseases.

Keywords: Autophagy; Prenatal nicotine exposure; Thymic hypoplasia; Thymus.

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Autophagy / drug effects
  • Beclin-1 / genetics
  • Beclin-1 / metabolism
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • Female
  • Immune System Diseases / chemically induced*
  • Immune System Diseases / immunology
  • Immune System Diseases / metabolism
  • Immune System Diseases / pathology
  • Male
  • Maternal Exposure
  • Mice, Inbred BALB C
  • Nicotine / toxicity*
  • Nicotinic Agonists / toxicity*
  • Ovalbumin / immunology
  • Phenotype
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Thymocytes / drug effects*
  • Thymocytes / immunology
  • Thymocytes / metabolism
  • Thymocytes / pathology
  • Thymus Gland / drug effects*
  • Thymus Gland / immunology
  • Thymus Gland / metabolism
  • Thymus Gland / pathology

Substances

  • Beclin-1
  • Becn1 protein, mouse
  • Nicotinic Agonists
  • Nicotine
  • Ovalbumin