{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:52:18Z","timestamp":1787237538266,"version":"build-2736575974"},"reference-count":60,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T00:00:00Z","timestamp":1574121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Brains & Behavior Seed Grant from Georgia State University"},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Georgia State University Next Generation New Scholars Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Many neural sex differences are differences in the number of neurons of a particular phenotype. For example, male rodents have more calbindin-expressing neurons in the medial preoptic area (mPOA) and bed nucleus of the stria terminalis (BNST), and females have more neurons expressing estrogen receptor alpha (ER\u03b1) and kisspeptin in the ventromedial nucleus of the hypothalamus (VMH) and the anteroventral periventricular nucleus (AVPV), respectively. These sex differences depend on neonatal exposure to testosterone, but the underlying molecular mechanisms are unknown. DNA methylation is important for cell phenotype differentiation throughout the developing organism. We hypothesized that testosterone causes sex differences in neurochemical phenotype via changes in DNA methylation, and tested this by inhibiting DNA methylation neonatally in male and female mice, and in females given a masculinizing dose of testosterone. Neonatal testosterone treatment masculinized calbindin, ER\u03b1 and kisspeptin cell number of females at weaning. Inhibiting DNA methylation with zebularine increased calbindin cell number only in control females, thus eliminating sex differences in calbindin in the mPOA and BNST. Zebularine also reduced the sex difference in ER\u03b1 cell number in the VMH, in this case by increasing ER\u03b1 neuron number in males and testosterone-treated females. In contrast, the neonatal inhibition of DNA methylation had no effect on kisspeptin cell number. We conclude that testosterone normally increases the number of calbindin cells and reduces ER\u03b1 cells in males through orchestrated changes in DNA methylation, contributing to, or causing, the sex differences in both cell types.<\/jats:p>","DOI":"10.1210\/endocr\/bqz022","type":"journal-article","created":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T06:29:18Z","timestamp":1574144958000},"source":"Crossref","is-referenced-by-count":32,"title":["Neonatal Inhibition of DNA Methylation Disrupts Testosterone-Dependent Masculinization of Neurochemical Phenotype"],"prefix":"10.1210","volume":"161","author":[{"given":"Carla D","family":"Cisternas","sequence":"first","affiliation":[{"name":"Neuroscience Institute, Georgia State University, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura R","family":"Cortes","sequence":"additional","affiliation":[{"name":"Neuroscience Institute, Georgia State University, Atlanta, 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