Oral Nicotine Alters Uterine Histo-Morphology but Does Not Disrupt the Estrous Cycle in Female Rats

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The primary goal of nicotine replacement therapy (NRT) is to reduce smoking related harms by introducing low nicotine products. In spite of being a potential mode of NRT, there is lack of information on the risks and safety of long term oral nicotine usage on the female reproductive system.


We evaluated the effects of 30 µg/mL oral nicotine consumption on the estrous cycle, circulating estradiol levels, and uterine and ovarian morphology after 2 or 7 weeks of intake by female Sprague-Dawley rats.


Estrous phase frequencies were similar between nicotine treated and control groups throughout the study, no changes were detected in nicotine-treated animals before and during the nicotine exposure period, and circulating estradiol levels were comparable between animals in both groups after 2 weeks of nicotine consumption. Histological examination of uteri from the nicotine group revealed a significant decrease in the height of uterine surface epithelium and an increase in the height of glandular epithelium compared to control animals; yet, the ovaries did not show attrition or changes in follicular appearance due to nicotine.


These preclinical studies suggest that nicotine intake results in structural changes in uterine tissues without disrupting estrous cyclicity or estradiol hormone levels. Though oral nicotine may not be totally risk-free, continuing research on this mode of nicotine administration is worthwhile to determine optimal dosing and duration of consumption for its potential use as an NRT.

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