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Developmental nicotine exposure and masculinization of the rat preoptic area.

Publication ,  Journal Article
Joglekar, R; Cauley, M; Lipsich, T; Corcoran, DL; Patisaul, HB; Levin, ED; Meyer, JN; McCarthy, MM; Murphy, SK
Published in: Neurotoxicology
March 2022

Nicotine is a neuroteratogenic component of tobacco smoke, e-cigarettes, and other products and can exert sex-specific effects in the developing brain, likely mediated through sex hormones. Estradiol modulates expression of nicotinic acetylcholine receptors in rats, and plays critical roles in neurodevelopmental processes, including sexual differentiation of the brain. Here, we examined the effects of developmental nicotine exposure on the sexual differentiation of the preoptic area (POA), a brain region that normally displays robust structural sexual dimorphisms and controls adult mating behavior in rodents. Using a rat model of gestational exposure, developing pups were exposed to nicotine (2 mg/kg/day) via maternal osmotic minipump (subcutaneously, sc) throughout the critical window for brain sexual differentiation. At postnatal day (PND) 4, a subset of offspring was analyzed for epigenetic effects in the POA. At PND40, all offspring were gonadectomized, implanted with a testosterone-releasing capsule (sc), and assessed for male sexual behavior at PND60. Following sexual behavior assessment, the area of the sexually dimorphic nucleus of the POA (SDN-POA) was measured using immunofluorescent staining techniques. In adults, normal sex differences in male sexual behavior and in the SDN-POA area were eliminated in nicotine-treated animals. Using novel analytical approaches to evaluate overall masculinization of the adult POA, we identified significant masculinization of the nicotine-treated female POA. In neonates (PND4), nicotine exposure induced trending alterations in methylation-dependent masculinizing gene expression and DNA methylation levels at sexually-dimorphic differentially methylated regions, suggesting that developmental nicotine exposure is capable of triggering masculinization of the rat POA via epigenetic mechanisms.

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Published In

Neurotoxicology

DOI

EISSN

1872-9711

Publication Date

March 2022

Volume

89

Start / End Page

41 / 54

Location

Netherlands

Related Subject Headings

  • Toxicology
  • Testosterone
  • Sex Differentiation
  • Sex Characteristics
  • Rats
  • Preoptic Area
  • Nicotine
  • Male
  • Female
  • Electronic Nicotine Delivery Systems
 

Citation

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Joglekar, R., Cauley, M., Lipsich, T., Corcoran, D. L., Patisaul, H. B., Levin, E. D., … Murphy, S. K. (2022). Developmental nicotine exposure and masculinization of the rat preoptic area. Neurotoxicology, 89, 41–54. https://doi.org/10.1016/j.neuro.2022.01.005
Joglekar, Rashmi, Marty Cauley, Taylor Lipsich, David L. Corcoran, Heather B. Patisaul, Edward D. Levin, Joel N. Meyer, Margaret M. McCarthy, and Susan K. Murphy. “Developmental nicotine exposure and masculinization of the rat preoptic area.Neurotoxicology 89 (March 2022): 41–54. https://doi.org/10.1016/j.neuro.2022.01.005.
Joglekar R, Cauley M, Lipsich T, Corcoran DL, Patisaul HB, Levin ED, et al. Developmental nicotine exposure and masculinization of the rat preoptic area. Neurotoxicology. 2022 Mar;89:41–54.
Joglekar, Rashmi, et al. “Developmental nicotine exposure and masculinization of the rat preoptic area.Neurotoxicology, vol. 89, Mar. 2022, pp. 41–54. Pubmed, doi:10.1016/j.neuro.2022.01.005.
Joglekar R, Cauley M, Lipsich T, Corcoran DL, Patisaul HB, Levin ED, Meyer JN, McCarthy MM, Murphy SK. Developmental nicotine exposure and masculinization of the rat preoptic area. Neurotoxicology. 2022 Mar;89:41–54.

Published In

Neurotoxicology

DOI

EISSN

1872-9711

Publication Date

March 2022

Volume

89

Start / End Page

41 / 54

Location

Netherlands

Related Subject Headings

  • Toxicology
  • Testosterone
  • Sex Differentiation
  • Sex Characteristics
  • Rats
  • Preoptic Area
  • Nicotine
  • Male
  • Female
  • Electronic Nicotine Delivery Systems