Developmental nicotine exposure and masculinization of the rat preoptic area.

Joglekar, Rashmi

Cauley, Marty

Lipsich, Taylor

Corcoran, David L

Patisaul, Heather B

Levin, Edward D

Meyer, Joel N

McCarthy, Margaret M

Murphy, Susan K

2023-12-06T14:25:14Z

2023-12-06T14:25:14Z

2022-03

2023-12-06T14:25:13Z

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.

S0161-813X(22)00013-4

0161-813X

1872-9711

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

eng

Elsevier BV

Neurotoxicology

10.1016/j.neuro.2022.01.005

Preoptic Area

Animals

Rats

Nicotine

Testosterone

Sex Differentiation

Sex Characteristics

Female

Male

Electronic Nicotine Delivery Systems

Developmental nicotine exposure and masculinization of the rat preoptic area.

Journal article

Levin, Edward D|0000-0002-5060-9602

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

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

41

54

Duke

Nicholas School of the Environment

School of Medicine

Trinity College of Arts & Sciences

Basic Science Departments

Clinical Science Departments

Institutes and Centers

Pharmacology & Cancer Biology

Obstetrics and Gynecology

Pathology

Psychiatry & Behavioral Sciences

Duke Cancer Institute

Psychology & Neuroscience

Environmental Sciences and Policy

Institutes and Provost's Academic Units

University Institutes and Centers

Duke Global Health Institute

Duke Institute for Brain Sciences

Initiatives

Duke Science & Society

Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences

Obstetrics and Gynecology, Reproductive Sciences

Published

89