ArticleDevelopmental biology2018
Luteinizing hormone signaling phosphorylates and activates the cyclic GMP phosphodiesterase PDE5 in mouse ovarian follicles, contributing an additional component to the hormonally induced decrease in cyclic GMP that reinitiates meiosis.
Article in Developmental biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 32 citations in OpenAlex.
- Intercellular cyclic nucleotide dynamics mediate oocyte meiosis in mammalian preovulatory follicles.Current topics in developmental biology · 2026Review
- Intercellular diffusion of cyclic nucleotides followed by gap junction closure restarts meiosis in mouse preovulatory follicles.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Investigating SMYD3 role during oocyte maturation in a 3D follicle-enclosed oocyteFrontiers in cell and developmental biology · 2025Article
- Phosphatases modified by LH signaling in ovarian follicles: testing their role in regulating the NPR2 guanylyl cyclase†.Biology of reproduction · 2024Article
- Application of amphiregulin in IVM culture of immature human oocytes and pre-insemination culture for COCs in IVF cycles.Frontiers in endocrinology · 2024Article
- Decreased HAT1 expression in granulosa cells disturbs oocyte meiosis during mouse ovarian aging.Reproductive biology and endocrinology : RB&E · 2023Article
- Phosphatases modified by LH signaling in ovarian follicles: testing their role in regulating the NPR2 guanylyl cyclase.bioRxiv : the preprint server for biology · 2023Article
- Article
- Effect ofBiology · 2023Article
- SphK-produced S1P in somatic cells is indispensable for LH-EGFR signaling-induced mouse oocyte maturation.Cell death & disease · 2022Article
- Epitope-tagged and phosphomimetic mouse models for investigating natriuretic peptide-stimulated receptor guanylyl cyclases.Frontiers in molecular neuroscience · 2022Article
- The mRNA-destabilizing protein Tristetraprolin targets "meiosis arrester"Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Cellular Heterogeneity of the Luteinizing Hormone Receptor and Its Significance for Cyclic GMP Signaling in Mouse Preovulatory Follicles.Endocrinology · 2020Article
- Granulosa secreted factors improve the developmental competence of cumulus oocyte complexes from small antral follicles in sheep.PloS one · 2020Article
- The art of oocyte meiotic arrest regulation.Reproductive biology and endocrinology : RB&E · 2019Review
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Authors and funding
3 authors at 1 institution in 1 country.
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Abstract
Prior to birth, oocytes within mammalian ovarian follicles initiate meiosis, but then arrest in prophase until puberty, when with each reproductive cycle, one or more follicles are stimulated by luteinizing hormone (LH) to resume meiosis in preparation for fertilization. Within preovulatory follicles, granulosa cells produce high levels of cGMP, which diffuses into the oocyte to maintain meiotic arrest. LH signaling restarts meiosis by rapidly lowering the levels of cGMP in the follicle and oocyte. Part of this decrease is mediated by the dephosphorylation and inactivation the NPR2 guanylyl cyclase in response to LH, but the mechanism for the remainder of the cGMP decrease is unknown. At least one cGMP phosphodiesterase, PDE5, is activated by LH signaling, which would contribute to lowering cGMP. PDE5 exhibits increased cGMP-hydrolytic activity when phosphorylated on serine 92, and we recently demonstrated that LH signaling phosphorylates PDE5 on this serine and increases its activity in rat follicles. To test the extent to which this mechanism contributes to the cGMP decrease that restarts meiosis, we generated a mouse line in which serine 92 was mutated to alanine (Pde5-S92A), such that it cannot be phosphorylated. Here we show that PDE5 phosphorylation is required for the LH-induced increase in cGMP-hydrolytic activity, but that this increase has only a modest effect on the LH-induced cGMP decrease in mouse follicles, and does not affect the timing of meiotic resumption. Though we show that the activation of PDE5 is among the mechanisms contributing to the cGMP decrease, these results suggest that another cGMP phosphodiesterase is also activated by LH signaling.
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