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The central CO\n                    <jats:sub>2<\/jats:sub>\n                    chemoreflex is a critical component of respiratory neural circuitry, as defects in these sensors cause hypoventilation syndromes, which are typically difficult to manage pharmacologically. Progesterone has long been known to stimulate breathing in both sexes, and remarkably, a potent progestin drug, etonogestrel (ETO), has been shown to enhance CO\n                    <jats:sub>2<\/jats:sub>\n                    \u2010chemosensitivity in animal models and in a subset of female patients affected by congenital central hypoventilation syndrome. Our recent work shows that systemic chronic ETO treatment recovered the CO\n                    <jats:sub>2<\/jats:sub>\n                    chemoreflex in female rats in which &lt;80% of neurons of the key CO\n                    <jats:sub>2<\/jats:sub>\n                    chemosensory structure of the retrotrapezoid nucleus (RTN) were eliminated, whereas male rats with similar lesions and ETO serum levels did not show recovery of the CO\n                    <jats:sub>2<\/jats:sub>\n                    chemoreflex. Interestingly, female respiratory recovery was associated with increased expression of the pH sensors\n                    <jats:italic>Task2<\/jats:italic>\n                    and\n                    <jats:italic>Gpr4<\/jats:italic>\n                    mRNA in the surviving RTN neurons, suggesting that progestin drugs may recover the CO\n                    <jats:sub>2<\/jats:sub>\n                    chemoreflex responses in a sex\u2010specific fashion.\n                  <\/jats:p>","DOI":"10.1111\/jne.70256","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:09:51Z","timestamp":1788865791000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["When\n                    <scp>\n                      CO\n                      <sub>2<\/sub>\n                    <\/scp>\n                    sensing fails: Protective effects of sex hormones and potential mechanisms"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2824-9487","authenticated-orcid":false,"given":"Tara A.","family":"Janes","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Dentistry University of Alberta  Edmonton Alberta Canada"},{"name":"Women and Children's Health Research Institute University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9758-2649","authenticated-orcid":false,"given":"Silvia","family":"Cardani","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Dentistry University of Alberta  Edmonton Alberta Canada"},{"name":"Women and Children's Health Research Institute University of Alberta  Edmonton Alberta 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