1. Leptin A deficiency affecting the mitochondrial dynamics of aged oocytes in medaka (Oryzias latipes).
- Author
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Yang J, Wang Y, Wang G, Guo Z, Li X, Lu J, Tu H, Li S, Wan J, Guan G, and Chen L
- Subjects
- Animals, Female, Autophagy genetics, Mitochondria metabolism, Mitochondria ultrastructure, Fertility genetics, Aging genetics, Aging metabolism, Ovary metabolism, Oryzias genetics, Oryzias metabolism, Oocytes metabolism, Leptin metabolism, Leptin genetics, Mitochondrial Dynamics genetics
- Abstract
Mitochondrial dysfunction and metabolic disorder have been associated to age-related subfertility, however, the precise molecular mechanism controlling the development of fertile oocytes in aging females remains elusive. Leptin plays an important role in the maintenance of energy homeostasis, as both excessive or insufficient levels can affect the body weight and fertility of mice. Here, we report that leptin A deficiency affects growth and shortens reproductive lifespan by reducing fertility in medaka (Oryzias latipes). Targeted disruption of lepa (lepa
-/- ) females reduced their egg laying and fertility compared to normal 3-month-old females (lepa+/+ sexual maturity), with symptoms worsening progressively at the age of 6 months and beyond. Transcriptomic analysis showed that differentially expressed genes involved in metabolic and mitochondrial pathways were significantly altered in lepa-/- ovaries compared with the normal ovaries at over 6 months old. The expression levels of the autophagy-promoting genes ulk1a, atg7 and atg12 were significantly differentiated between normal and lepa-/- ovaries, which were further confirmed by quantitative polymerase chain reaction analysis, indicating abnormal autophagy activation and mitochondrial dysfunction in oocyte development lacking lepa. Transmission electron microscopy observations further confirmed these mitochondrial disorders in lepa-deficient oocytes. In summary, these research findings provide novel insights into how leptin influences female fertility through mitochondrial-mediated oocyte development., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest regarding the contents of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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