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Publication : Reproductive, Physiological, and Molecular Outcomes in Female Mice Deficient in Dhh and Ihh.

First Author  Liu C Year  2018
Journal  Endocrinology Volume  159
Issue  7 Pages  2563-2575
PubMed ID  29788357 Mgi Jnum  J:263773
Mgi Id  MGI:6188819 Doi  10.1210/en.2018-00095
Citation  Liu C, et al. (2018) Reproductive, Physiological, and Molecular Outcomes in Female Mice Deficient in Dhh and Ihh. Endocrinology 159(7):2563-2575
abstractText  Ovarian development requires coordinate communications among oocytes, granulosa cells, and theca cells. Two Hedgehog (Hh) pathway ligands, Desert hedgehog (Dhh) and Indian hedgehog (Ihh), are produced by the granulosa cells and work together to regulate theca cell specification and development. Mice lacking both Dhh and Ihh had loss of normal ovarian function, which raised the question of which biological actions are specifically controlled by each ligand during folliculogenesis. By comparing the reproductive fitness, hormonal profiles, and ovarian transcriptomes among control, Dhh single-knockout (KO), Ihh KO, and Dhh/Ihh double-knockout (DKO) mice, we examined the specific roles of Dhh and Ihh in these processes. Dhh/Ihh DKO female mice were infertile because of a lack of theca cells and their steroid product androgen. Although Dhh and Ihh KO mice were fertile with normal folliculogenesis, they had decreased androgen production and alterations in their ovarian transcriptomes. Absence of Ihh led to aberrant steroidogenesis and elevated inflammation responses, which were not found in Dhh KO mouse ovaries, implicating that IHH has a greater impact than DHH on the activation of the Hh signaling pathway in the ovary. Our findings provide insight into not only how the Hh pathway influences folliculogenesis but also the distinct and overlapping roles of Dhh and Ihh in supporting ovarian development.
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