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dc.contributor.authorQiu, Lianglin
dc.contributor.authorChen, Minjie
dc.contributor.authorWang, Xiaoke
dc.contributor.authorChen, Sufang
dc.contributor.authorYing, Zhekang
dc.date.accessioned2021-09-13T13:54:19Z
dc.date.available2021-09-13T13:54:19Z
dc.date.issued2021-09-08
dc.identifier.urihttp://hdl.handle.net/10713/16587
dc.description.abstractEpidemiological studies have shown that exposure to ambient fine particulate matter with aerodynamic diameter less than or equal to 2.5 μm (PM2.5) correlates with a decrease in sperm count, but the biological mechanism remains elusive. Objectives: This study tested whether hypothalamic inflammation, an emerging pathophysiological mediator, mediates the development of lower epididymal sperm count due to PM2.5 exposure. Methods: Inhibitor κB kinase 2 (IKK2) was conditionally knocked out either in all neurons or subtypes of hypothalamic neurons of mice. Effects of concentrated ambient PM2.5 (CAP) exposure on hypothalamic inflammation, the hypothalamic–pituitary–gonadal (HPG) axis, and epididymal sperm count of these mouse models were then assessed. Furthermore, to test whether hypothalamic inflammation is sufficient to decrease sperm production, we overexpressed constitutively active IKK2 (IKK2ca) either in all neurons or subtypes of hypothalamic neurons and assessed hypothalamic inflammation, the HPG axis, and sperm production of these overexpression mouse models. Results: CAP-exposed wild-type control mice vs. filtered air (FA)-exposed wild-type control mice had a higher expression of hypothalamic inflammatory markers, lower functional indexes of the HPG axis, and a lower epididymal sperm count. In contrast, all these measurements for CAP- vs. FA-exposed mice deficient of IKK2 in all neurons were comparable. We also found that overexpression of IKK2ca in either all neurons or pro-opiomelanocortin (POMC) neurons only, but not in Agouti-related protein (AgRP) neurons only, resulted in lower functional indexes of the HPG axis and a lower epididymal sperm count. Moreover, we showed that CAP- vs. FA-exposed mice deficient of IKK2 in POMC neurons had a comparable expression of hypothalamic inflammatory markers, comparable functional indexes of the HPG axis, and a comparable epididymal sperm count. Discussion: This mouse model study shows a causal role of IKK2 of POMC neurons in the development of lower epididymal sperm count due to PM2.5 exposure, providing a mechanistic insight into this emerging pathogenesis.en_US
dc.description.urihttps://doi.org/10.1289/EHP8868en_US
dc.description.urihttp://www.ncbi.nlm.nih.gov/pmc/articles/pmc8425520/en_US
dc.language.isoenen_US
dc.publisherResearch Triangle Park, N. C. National Institute of Environmental Health Sciencesen_US
dc.relation.ispartofEnvironmental Health Perspectivesen_US
dc.subjectinhibitor kB kinase 2 (IKK2)en_US
dc.subject.meshMiceen_US
dc.subject.meshNeuronsen_US
dc.subject.meshParticulate Matter--adverse effectsen_US
dc.subject.meshPro-Opiomelanocortin (POMC)en_US
dc.subject.meshSpermatogenesisen_US
dc.titleExposure of Mice during Spermatogenesis: A Role of Inhibitor Kinase 2 in Pro-Opiomelanocortin Neuronsen_US
dc.typeArticleen_US
dc.identifier.doi10.1289/EHP8868
dc.identifier.pmid34495743
dc.source.volume129
dc.source.issue9
dc.source.beginpage97006
dc.source.endpage
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States


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