Abstract

BackgroundThe use of multiwalled carbon nanotubes (MWCNT) is increasing due to a growing use in a variety of products across several industries. Thus, occupational exposure is also of increasing concern, particularly since airway exposure to MWCNTs can induce sustained pulmonary acute phase response and inflammation in experimental animals, which may affect female reproduction. This proof-of-principle study therefore aimed to investigate if lung exposure by intratracheal instillation of the MWCNT NM-400 would affect the estrous cycle and reproductive function in female mice.ResultsEstrous cycle regularity was investigated by comparing vaginal smears before and after exposure to 67 μg of NM-400, whereas reproductive function was analyzed by measuring time to delivery of litters after instillation of 2, 18 or 67 μg of NM-400. Compared to normal estrous cycling determined prior to exposure, exposure to MWCNT significantly prolonged the estrous cycle during which exposure took place, but significantly shortened the estrous cycle immediately after the exposed cycle. No consistent effects were seen on time to delivery of litter or other gestational or litter parameters, such as litter size, sex ratio, implantations and implantation loss.ConclusionLung exposure to MWCNT interfered with estrous cycling. Effects caused by MWCNTs depended on the time of exposure: the estrous stage was particularly sensitive to exposure, as animals exposed during this stage showed a higher incidence of irregular cycling after exposure. Our data indicates that MWCNT exposure may interfere with events leading to ovulation.

Highlights

  • The use of multiwalled carbon nanotubes (MWCNT) is increasing due to a growing use in a variety of products across several industries

  • We have investigated the effects on female reproduction following pulmonary exposure to the MWCNT NM-400

  • The first experiment investigated whether exposure to MWCNT could disrupt estrous cycling, whereas the second experiment assessed if time to delivery of litter, and establishment of pregnancy, was affected by MWCNT exposure

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Summary

Introduction

The use of multiwalled carbon nanotubes (MWCNT) is increasing due to a growing use in a variety of products across several industries. Occupational exposure is of increasing concern, since airway exposure to MWCNTs can induce sustained pulmonary acute phase response and inflammation in experimental animals, which may affect female reproduction. It has been shown that airway exposure to MWCNTs can induce sustained pulmonary acute phase response and inflammation in the lungs This is characterized by influx of neutrophilic granulocytes, as well as the production of acute phase protein (Serum Amyloid A, SAA) and cytokines such as IL-1β, IL6 and TNF-α [3, 4], which may lead to systemic inflammation if secreted into the circulation [5,6,7,8,9]. A series of in vivo studies on ewes exposed to endotoxin has shown that inflammation can disrupt the female reproductive axis by for instance disrupting hypothalamic or pituitary signaling leading to impaired reproductive capacity [15,16,17,18]

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