Estradiol Reverses Ovariectomy-Induced Disruption of Hypothalamic Gene Expression and Behavior via Modulation of Gonadotropin Releasing Hormone and Calcium Signaling Pathways
Estrogen plays a crucial role in regulating reproductive and neuroendocrine functions, yet the molecular mechanisms underlying its effects on the hypothalamus remain incompletely understood. This study investigates the transcriptional and behavioral changes induced by ovariectomy (OVX) and estradiol...
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2025-05-01
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| author | Asim Muhammad Mubashir Muhammad Xiaohuan Chao Chunlei Zhang Jiahao Chen Huan Yang Shuhan Liu Yuan Ding Ziming Wang Hongwei Bi Wen Guo Junhong Fan Bo Zhou |
| author_facet | Asim Muhammad Mubashir Muhammad Xiaohuan Chao Chunlei Zhang Jiahao Chen Huan Yang Shuhan Liu Yuan Ding Ziming Wang Hongwei Bi Wen Guo Junhong Fan Bo Zhou |
| author_sort | Asim Muhammad |
| collection | DOAJ |
| description | Estrogen plays a crucial role in regulating reproductive and neuroendocrine functions, yet the molecular mechanisms underlying its effects on the hypothalamus remain incompletely understood. This study investigates the transcriptional and behavioral changes induced by ovariectomy (OVX) and estradiol (E2) supplementation in female C57BL/6J mice. RNA sequencing was performed to identify differentially expressed genes (DEGs) across control (CK), E2, OVX, and OVX+E2 groups, followed by functional enrichment and pathway analyses. Behavioral assessments, including open field, Y-maze, and elevated plus maze tests, were conducted to evaluate anxiety-like and cognitive behaviors. Results revealed significant alterations in GnRH signaling, neurotransmission, and inflammatory pathways, with key genes such as <i>Elk1</i>, <i>Prkcb</i>, and <i>Camk2a</i> differentially expressed in response to estrogen modulation. OVX-induced neuroendocrine disruptions were partially reversed by E2 treatment, as evidenced by transcriptomic and behavioral outcomes. Pearson correlation analysis further linked gene expression patterns with phenotypic traits, providing insights into estrogen’s regulatory mechanisms in the hypothalamus. These findings enhance our understanding of estrogen-mediated neuroendocrine regulation and may have implications for hormone replacement therapies in postmenopausal disorders. |
| format | Article |
| id | doaj-art-6612d7fe7b5944a1b3ec99302a3cba8e |
| institution | OA Journals |
| issn | 2076-2615 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Animals |
| spelling | doaj-art-6612d7fe7b5944a1b3ec99302a3cba8e2025-08-20T02:33:39ZengMDPI AGAnimals2076-26152025-05-011510146710.3390/ani15101467Estradiol Reverses Ovariectomy-Induced Disruption of Hypothalamic Gene Expression and Behavior via Modulation of Gonadotropin Releasing Hormone and Calcium Signaling PathwaysAsim Muhammad0Mubashir Muhammad1Xiaohuan Chao2Chunlei Zhang3Jiahao Chen4Huan Yang5Shuhan Liu6Yuan Ding7Ziming Wang8Hongwei Bi9Wen Guo10Junhong Fan11Bo Zhou12College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaEstrogen plays a crucial role in regulating reproductive and neuroendocrine functions, yet the molecular mechanisms underlying its effects on the hypothalamus remain incompletely understood. This study investigates the transcriptional and behavioral changes induced by ovariectomy (OVX) and estradiol (E2) supplementation in female C57BL/6J mice. RNA sequencing was performed to identify differentially expressed genes (DEGs) across control (CK), E2, OVX, and OVX+E2 groups, followed by functional enrichment and pathway analyses. Behavioral assessments, including open field, Y-maze, and elevated plus maze tests, were conducted to evaluate anxiety-like and cognitive behaviors. Results revealed significant alterations in GnRH signaling, neurotransmission, and inflammatory pathways, with key genes such as <i>Elk1</i>, <i>Prkcb</i>, and <i>Camk2a</i> differentially expressed in response to estrogen modulation. OVX-induced neuroendocrine disruptions were partially reversed by E2 treatment, as evidenced by transcriptomic and behavioral outcomes. Pearson correlation analysis further linked gene expression patterns with phenotypic traits, providing insights into estrogen’s regulatory mechanisms in the hypothalamus. These findings enhance our understanding of estrogen-mediated neuroendocrine regulation and may have implications for hormone replacement therapies in postmenopausal disorders.https://www.mdpi.com/2076-2615/15/10/1467ovariectomyestradiol interventionhypothalamic transcriptomicsGnRH signaling pathwaycalcium signaling pathwayreproductive aging |
| spellingShingle | Asim Muhammad Mubashir Muhammad Xiaohuan Chao Chunlei Zhang Jiahao Chen Huan Yang Shuhan Liu Yuan Ding Ziming Wang Hongwei Bi Wen Guo Junhong Fan Bo Zhou Estradiol Reverses Ovariectomy-Induced Disruption of Hypothalamic Gene Expression and Behavior via Modulation of Gonadotropin Releasing Hormone and Calcium Signaling Pathways Animals ovariectomy estradiol intervention hypothalamic transcriptomics GnRH signaling pathway calcium signaling pathway reproductive aging |
| title | Estradiol Reverses Ovariectomy-Induced Disruption of Hypothalamic Gene Expression and Behavior via Modulation of Gonadotropin Releasing Hormone and Calcium Signaling Pathways |
| title_full | Estradiol Reverses Ovariectomy-Induced Disruption of Hypothalamic Gene Expression and Behavior via Modulation of Gonadotropin Releasing Hormone and Calcium Signaling Pathways |
| title_fullStr | Estradiol Reverses Ovariectomy-Induced Disruption of Hypothalamic Gene Expression and Behavior via Modulation of Gonadotropin Releasing Hormone and Calcium Signaling Pathways |
| title_full_unstemmed | Estradiol Reverses Ovariectomy-Induced Disruption of Hypothalamic Gene Expression and Behavior via Modulation of Gonadotropin Releasing Hormone and Calcium Signaling Pathways |
| title_short | Estradiol Reverses Ovariectomy-Induced Disruption of Hypothalamic Gene Expression and Behavior via Modulation of Gonadotropin Releasing Hormone and Calcium Signaling Pathways |
| title_sort | estradiol reverses ovariectomy induced disruption of hypothalamic gene expression and behavior via modulation of gonadotropin releasing hormone and calcium signaling pathways |
| topic | ovariectomy estradiol intervention hypothalamic transcriptomics GnRH signaling pathway calcium signaling pathway reproductive aging |
| url | https://www.mdpi.com/2076-2615/15/10/1467 |
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