Semaphorin 3E‐Plexin‐D1 Pathway Downstream of the Luteinizing Hormone Surge Regulates Ovulation, Granulosa Cell Luteinization, and Ovarian Angiogenesis in Mice
Abstract Ovulation is induced by the luteinizing hormone (LH) surge and accompanied by granulosa cell luteinization and ovarian angiogenesis. Semaphorin 3E (Sema3E)‐Plexin‐D1 pathway regulates angiogenesis in other tissues, but its role in the ovary is unknown. Evidence indicates that Sema3E‐Plexin‐...
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Wiley
2025-08-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202417163 |
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| author | Hanxue Zhang Jimmy Dhillon Paul D. Soloway Bo Shui Seoyeon Lee Jennifer K. Grenier Paul R. Munn M. Cecilia Ljungberg Rebecca B Williams Rainer B. Lanz Yu‐Hsiang Liao Yi A. Ren |
| author_facet | Hanxue Zhang Jimmy Dhillon Paul D. Soloway Bo Shui Seoyeon Lee Jennifer K. Grenier Paul R. Munn M. Cecilia Ljungberg Rebecca B Williams Rainer B. Lanz Yu‐Hsiang Liao Yi A. Ren |
| author_sort | Hanxue Zhang |
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| description | Abstract Ovulation is induced by the luteinizing hormone (LH) surge and accompanied by granulosa cell luteinization and ovarian angiogenesis. Semaphorin 3E (Sema3E)‐Plexin‐D1 pathway regulates angiogenesis in other tissues, but its role in the ovary is unknown. Evidence indicates that Sema3E‐Plexin‐D1 pathway plays an important role in the mouse ovary. The expression of Sema3E and its receptor, Plexin‐D1, is dynamically regulated in the mouse ovary downstream of the LH surge. This regulation requires the modulation of chromatin accessibility by CCAAT/enhancer‐binding proteins α and β. Intraovarian injection of recombinant Sema3E results in reduced ovulation, impaired corpus luteum formation, and aberrant ovarian angiogenesis. These in vivo physiological abnormalities are consistent with altered expression of genes regulating these processes, and with data from in vitro cultured granulosa cells and ovarian stromal tissues treated with Sema3E or neutralizing antibody of Plexin‐D1. The findings pinpoint Sema3E‐Plexin‐D1 pathway as a potential therapeutic target for fertility and infertility management. |
| format | Article |
| id | doaj-art-340888cf3d5e477da2daba2208ef2023 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj-art-340888cf3d5e477da2daba2208ef20232025-08-20T04:01:15ZengWileyAdvanced Science2198-38442025-08-011229n/an/a10.1002/advs.202417163Semaphorin 3E‐Plexin‐D1 Pathway Downstream of the Luteinizing Hormone Surge Regulates Ovulation, Granulosa Cell Luteinization, and Ovarian Angiogenesis in MiceHanxue Zhang0Jimmy Dhillon1Paul D. Soloway2Bo Shui3Seoyeon Lee4Jennifer K. Grenier5Paul R. Munn6M. Cecilia Ljungberg7Rebecca B Williams8Rainer B. Lanz9Yu‐Hsiang Liao10Yi A. Ren11Department of Animal Science College of Agriculture and Life Sciences Cornell University Ithaca NY 14853 USADepartment of Biomedical Sciences College of Veterinary Medicine Cornell University Ithaca NY 14853 USADepartment of Biomedical Sciences College of Veterinary Medicine Cornell University Ithaca NY 14853 USADepartment of Biomedical Sciences College of Veterinary Medicine Cornell University Ithaca NY 14853 USADepartment of Biomedical Sciences College of Veterinary Medicine Cornell University Ithaca NY 14853 USAGenomics Innovation Hub Biotechnology Resource Center Cornell University Ithaca NY 14853 USAGenomics Innovation Hub Biotechnology Resource Center Cornell University Ithaca NY 14853 USADepartment of Pediatrics Baylor College of Medicine Houston TX 77030 USABiotechnology Resource Center Imaging Facility Cornell University Ithaca NY 14853 USADepartment of Molecular and Cellular Biology Baylor College of Medicine Houston TX 77030 USADepartment of Animal Science College of Agriculture and Life Sciences Cornell University Ithaca NY 14853 USADepartment of Animal Science College of Agriculture and Life Sciences Cornell University Ithaca NY 14853 USAAbstract Ovulation is induced by the luteinizing hormone (LH) surge and accompanied by granulosa cell luteinization and ovarian angiogenesis. Semaphorin 3E (Sema3E)‐Plexin‐D1 pathway regulates angiogenesis in other tissues, but its role in the ovary is unknown. Evidence indicates that Sema3E‐Plexin‐D1 pathway plays an important role in the mouse ovary. The expression of Sema3E and its receptor, Plexin‐D1, is dynamically regulated in the mouse ovary downstream of the LH surge. This regulation requires the modulation of chromatin accessibility by CCAAT/enhancer‐binding proteins α and β. Intraovarian injection of recombinant Sema3E results in reduced ovulation, impaired corpus luteum formation, and aberrant ovarian angiogenesis. These in vivo physiological abnormalities are consistent with altered expression of genes regulating these processes, and with data from in vitro cultured granulosa cells and ovarian stromal tissues treated with Sema3E or neutralizing antibody of Plexin‐D1. The findings pinpoint Sema3E‐Plexin‐D1 pathway as a potential therapeutic target for fertility and infertility management.https://doi.org/10.1002/advs.202417163granulosa cell luteinizationovarian angiogenesispreovulatoryPlexin‐D1Semaphorin 3E |
| spellingShingle | Hanxue Zhang Jimmy Dhillon Paul D. Soloway Bo Shui Seoyeon Lee Jennifer K. Grenier Paul R. Munn M. Cecilia Ljungberg Rebecca B Williams Rainer B. Lanz Yu‐Hsiang Liao Yi A. Ren Semaphorin 3E‐Plexin‐D1 Pathway Downstream of the Luteinizing Hormone Surge Regulates Ovulation, Granulosa Cell Luteinization, and Ovarian Angiogenesis in Mice Advanced Science granulosa cell luteinization ovarian angiogenesis preovulatory Plexin‐D1 Semaphorin 3E |
| title | Semaphorin 3E‐Plexin‐D1 Pathway Downstream of the Luteinizing Hormone Surge Regulates Ovulation, Granulosa Cell Luteinization, and Ovarian Angiogenesis in Mice |
| title_full | Semaphorin 3E‐Plexin‐D1 Pathway Downstream of the Luteinizing Hormone Surge Regulates Ovulation, Granulosa Cell Luteinization, and Ovarian Angiogenesis in Mice |
| title_fullStr | Semaphorin 3E‐Plexin‐D1 Pathway Downstream of the Luteinizing Hormone Surge Regulates Ovulation, Granulosa Cell Luteinization, and Ovarian Angiogenesis in Mice |
| title_full_unstemmed | Semaphorin 3E‐Plexin‐D1 Pathway Downstream of the Luteinizing Hormone Surge Regulates Ovulation, Granulosa Cell Luteinization, and Ovarian Angiogenesis in Mice |
| title_short | Semaphorin 3E‐Plexin‐D1 Pathway Downstream of the Luteinizing Hormone Surge Regulates Ovulation, Granulosa Cell Luteinization, and Ovarian Angiogenesis in Mice |
| title_sort | semaphorin 3e plexin d1 pathway downstream of the luteinizing hormone surge regulates ovulation granulosa cell luteinization and ovarian angiogenesis in mice |
| topic | granulosa cell luteinization ovarian angiogenesis preovulatory Plexin‐D1 Semaphorin 3E |
| url | https://doi.org/10.1002/advs.202417163 |
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