Female fertility does not require Bmal1 in suprachiasmatic nucleus neurons expressing arginine vasopressin, vasoactive intestinal peptide, or neuromedin-S
Disruptions to the circadian system alter reproductive capacity, particularly in females. Mice lacking the core circadian clock gene, Bmal1, are infertile and have evidence of neuroendocrine disruption including the absence of the preovulatory luteinizing hormone (LH) surge and enhanced responsivene...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.956169/full |
| _version_ | 1818537084821962752 |
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| author | Karen J. Tonsfeldt Karen J. Tonsfeldt Laura J. Cui Jinkwon Lee Thijs J. Walbeek Liza E. Brusman Ye Jin Michihiro Mieda Michael R. Gorman Michael R. Gorman Pamela L. Mellon Pamela L. Mellon |
| author_facet | Karen J. Tonsfeldt Karen J. Tonsfeldt Laura J. Cui Jinkwon Lee Thijs J. Walbeek Liza E. Brusman Ye Jin Michihiro Mieda Michael R. Gorman Michael R. Gorman Pamela L. Mellon Pamela L. Mellon |
| author_sort | Karen J. Tonsfeldt |
| collection | DOAJ |
| description | Disruptions to the circadian system alter reproductive capacity, particularly in females. Mice lacking the core circadian clock gene, Bmal1, are infertile and have evidence of neuroendocrine disruption including the absence of the preovulatory luteinizing hormone (LH) surge and enhanced responsiveness to exogenous kisspeptin. Here, we explore the role of Bmal1 in suprachiasmatic nucleus (SCN) neuron populations known to project to the neuroendocrine axis. We generated four mouse lines using Cre/Lox technology to create conditional deletion of Bmal1 in arginine vasopressin (Bmal1fl/fl:Avpcre), vasoactive intestinal peptide (Bmal1fl/fl:Vipcre), both (Bmal1fl/fl:Avpcre+Vipcre), and neuromedin-s (Bmal1fl/fl:Nmscre) neurons. We demonstrate that the loss of Bmal1 in these populations has substantial effects on home-cage circadian activity and temperature rhythms. Despite this, we found that female mice from these lines demonstrated normal estrus cycles, fecundity, kisspeptin responsiveness, and inducible LH surge. We found no evidence of reproductive disruption in constant darkness. Overall, our results indicate that while conditional Bmal1 knockout in AVP, VIP, or NMS neurons is sufficient to disrupted locomotor activity, this disruption is insufficient to recapitulate the neuroendocrine reproductive effects of the whole-body Bmal1 knockout. |
| first_indexed | 2024-12-11T18:46:12Z |
| format | Article |
| id | doaj.art-ccc8699a188a4143890678faf2da2f60 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-11T18:46:12Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-ccc8699a188a4143890678faf2da2f602022-12-22T00:54:28ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-08-011310.3389/fendo.2022.956169956169Female fertility does not require Bmal1 in suprachiasmatic nucleus neurons expressing arginine vasopressin, vasoactive intestinal peptide, or neuromedin-SKaren J. Tonsfeldt0Karen J. Tonsfeldt1Laura J. Cui2Jinkwon Lee3Thijs J. Walbeek4Liza E. Brusman5Ye Jin6Michihiro Mieda7Michael R. Gorman8Michael R. Gorman9Pamela L. Mellon10Pamela L. Mellon11Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, United StatesCenter for Circadian Biology, University of California, San Diego, La Jolla, CA, United StatesDepartment of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, United StatesDepartment of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, United StatesDepartment of Psychology, University of California, San Diego, La Jolla, CA, United StatesDepartment of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, United StatesDepartment of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, United StatesDepartment of Integrative Neurophysiology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, JapanCenter for Circadian Biology, University of California, San Diego, La Jolla, CA, United StatesDepartment of Psychology, University of California, San Diego, La Jolla, CA, United StatesDepartment of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, United StatesCenter for Circadian Biology, University of California, San Diego, La Jolla, CA, United StatesDisruptions to the circadian system alter reproductive capacity, particularly in females. Mice lacking the core circadian clock gene, Bmal1, are infertile and have evidence of neuroendocrine disruption including the absence of the preovulatory luteinizing hormone (LH) surge and enhanced responsiveness to exogenous kisspeptin. Here, we explore the role of Bmal1 in suprachiasmatic nucleus (SCN) neuron populations known to project to the neuroendocrine axis. We generated four mouse lines using Cre/Lox technology to create conditional deletion of Bmal1 in arginine vasopressin (Bmal1fl/fl:Avpcre), vasoactive intestinal peptide (Bmal1fl/fl:Vipcre), both (Bmal1fl/fl:Avpcre+Vipcre), and neuromedin-s (Bmal1fl/fl:Nmscre) neurons. We demonstrate that the loss of Bmal1 in these populations has substantial effects on home-cage circadian activity and temperature rhythms. Despite this, we found that female mice from these lines demonstrated normal estrus cycles, fecundity, kisspeptin responsiveness, and inducible LH surge. We found no evidence of reproductive disruption in constant darkness. Overall, our results indicate that while conditional Bmal1 knockout in AVP, VIP, or NMS neurons is sufficient to disrupted locomotor activity, this disruption is insufficient to recapitulate the neuroendocrine reproductive effects of the whole-body Bmal1 knockout.https://www.frontiersin.org/articles/10.3389/fendo.2022.956169/fullcircadian clockfertilityluteinizing hormone surgearginine vasopressinvasoactive intestinal peptideneuromedin-s |
| spellingShingle | Karen J. Tonsfeldt Karen J. Tonsfeldt Laura J. Cui Jinkwon Lee Thijs J. Walbeek Liza E. Brusman Ye Jin Michihiro Mieda Michael R. Gorman Michael R. Gorman Pamela L. Mellon Pamela L. Mellon Female fertility does not require Bmal1 in suprachiasmatic nucleus neurons expressing arginine vasopressin, vasoactive intestinal peptide, or neuromedin-S Frontiers in Endocrinology circadian clock fertility luteinizing hormone surge arginine vasopressin vasoactive intestinal peptide neuromedin-s |
| title | Female fertility does not require Bmal1 in suprachiasmatic nucleus neurons expressing arginine vasopressin, vasoactive intestinal peptide, or neuromedin-S |
| title_full | Female fertility does not require Bmal1 in suprachiasmatic nucleus neurons expressing arginine vasopressin, vasoactive intestinal peptide, or neuromedin-S |
| title_fullStr | Female fertility does not require Bmal1 in suprachiasmatic nucleus neurons expressing arginine vasopressin, vasoactive intestinal peptide, or neuromedin-S |
| title_full_unstemmed | Female fertility does not require Bmal1 in suprachiasmatic nucleus neurons expressing arginine vasopressin, vasoactive intestinal peptide, or neuromedin-S |
| title_short | Female fertility does not require Bmal1 in suprachiasmatic nucleus neurons expressing arginine vasopressin, vasoactive intestinal peptide, or neuromedin-S |
| title_sort | female fertility does not require bmal1 in suprachiasmatic nucleus neurons expressing arginine vasopressin vasoactive intestinal peptide or neuromedin s |
| topic | circadian clock fertility luteinizing hormone surge arginine vasopressin vasoactive intestinal peptide neuromedin-s |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.956169/full |
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