Developmental nicotine exposure and masculinization of the rat preoptic area.

dc.contributor.author

Joglekar, Rashmi

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Cauley, Marty

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Lipsich, Taylor

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Corcoran, David L

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Patisaul, Heather B

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Levin, Edward D

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Meyer, Joel N

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McCarthy, Margaret M

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Murphy, Susan K

dc.date.accessioned

2023-12-06T14:25:14Z

dc.date.available

2023-12-06T14:25:14Z

dc.date.issued

2022-03

dc.date.updated

2023-12-06T14:25:13Z

dc.description.abstract

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.

dc.identifier

S0161-813X(22)00013-4

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0161-813X

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1872-9711

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https://hdl.handle.net/10161/29480

dc.language

eng

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Elsevier BV

dc.relation.ispartof

Neurotoxicology

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10.1016/j.neuro.2022.01.005

dc.subject

Preoptic Area

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Animals

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Rats

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Nicotine

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Testosterone

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Sex Differentiation

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Sex Characteristics

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Female

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Male

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Electronic Nicotine Delivery Systems

dc.title

Developmental nicotine exposure and masculinization of the rat preoptic area.

dc.type

Journal article

duke.contributor.orcid

Levin, Edward D|0000-0001-7292-8084|0000-0002-5060-9602

duke.contributor.orcid

Meyer, Joel N|0000-0003-1219-0983

duke.contributor.orcid

Murphy, Susan K|0000-0001-8298-7272

pubs.begin-page

41

pubs.end-page

54

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Duke

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Nicholas School of the Environment

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School of Medicine

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Trinity College of Arts & Sciences

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Pharmacology & Cancer Biology

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Obstetrics and Gynecology

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Pathology

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Psychiatry & Behavioral Sciences

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Duke Cancer Institute

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Psychology & Neuroscience

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Environmental Sciences and Policy

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Institutes and Provost's Academic Units

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University Institutes and Centers

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Duke Global Health Institute

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Duke Institute for Brain Sciences

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Duke Science & Society

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Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences

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Published

pubs.volume

89

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