Multiple roles of hypoxia in bovine corpus luteum

Nishimura, Ryo; Okuda, Kiyoshi

doi:10.1262/jrd.2020-018

Cited by 11 publications

(6 citation statements)

References 50 publications

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“…This is an important finding implying an active local regulation of HIF1α availability within the ovary, possibly preventing its exaggeratedly high levels and thereby supporting the underlying hypothesis of the present study. Interestingly, the regressing CL in particular seemed to stain more weakly, supporting the higher availability of functionally active HIF1α during luteal regression observed in other species, for example, in the cow or dog (Nishimura et al 2006;Sousa et al 2016;Nishimura and Okuda 2020).…”

Section: Discussionsupporting

confidence: 55%

“…However, during early luteal development, angiogenesis falls behind the intense luteal cell proliferation and the O 2 supply is further limited (Amselgruber et al 1999). Similarly, during luteal regression, reduced vascular density leads again to hypoxia, thereby contributing to functional and structural luteolysis (Meidan et al 2013;Nishimura and Okuda 2020). Cumulatively, hypoxia plays important roles in regulating reproductive events, including follicular and luteal function.…”

Section: Introductionmentioning

confidence: 99%

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The involvement of hypoxia-inducible factor 1α (HIF1α)-stabilising factors in steroidogenic acute regulatory (STAR) protein-dependent steroidogenesis in murine KK1 granulosa cells

Gysin

Kowalewski

2021

Reprod. Fertil. Dev.

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As a component of hypoxia-inducible factor1 (HIF1)-complexes, HIF1α regulates the expression of steroidogenic acute regulatory (STAR) protein in granulosa cells. However, severe hypoxia or exaggeratedly expressed HIF1α have detrimental effects. HIF1α is regulated by factor inhibiting HIF (FIH), prolyl hydroxylases (PHD1, 2, 3) and von Hippel-Lindau (VHL) suppressor protein. In this study, the expression of FIH, PHD1, 2, 3 and VHL was investigated in murine ovaries and immortalised KK1 granulosa cells. We found FIH, VHL and PHD2 transcripts predominantly in growing tertiary follicles. Functional aspects were assessed in KK1 cells exposed to decreasing O2 (20%, 10%, 1%), by determining HIF1α, FIH, VHL, PHD1–3 and STAR expression. The main findings indicated gradually increasing PHD2 under lowered O2. Functional blocking of PHDs revealed biphasic effects on STAR expression; concomitantly with increasing HIF1α, STAR expression, which was initially induced, decreased significantly when HIF1α was strongly stabilised. Finally, PHD2 in particular might act as a specific regulator of HIF1α and, thereby, of STAR availability in granulosa cells.

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Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

The involvement of hypoxia-inducible factor 1α (HIF1α)-stabilising factors in steroidogenic acute regulatory (STAR) protein-dependent steroidogenesis in murine KK1 granulosa cells

Gysin

Kowalewski

2021

Reprod. Fertil. Dev.

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“…Corpus luteum is a transient endocrine gland that develops from residual follicular tissues after ovulation in the presence of active angiogenesis [ 79 ]. The ruptured follicle is under hypoxia conditions after ovulation, when hypoxia-inducible factor-1 (HIF1) is induced and promotes the angiogenesis of corpus luteum via VEGF [ 62 ]. Besides the formation of corpus luteum, VEGF also contributes to progesterone production by corpus luteum [ 63 ].…”

Section: The Role Of Vegf In the Reproductive System During Embryomentioning

confidence: 99%

Role of Vascular Endothelial Growth Factor (VEGF) in Human Embryo Implantation: Clinical Implications

Guo

et al. 2021

Biomolecules

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Vascular endothelial growth factor (VEGF) is a well-known angiogenic factor that plays a critical role in various physiological and pathological processes. VEGF also contributes to the process of embryo implantation by enhancing embryo development, improving endometrial receptivity, and facilitating the interactions between the developing embryo and the endometrium. There is a correlation between the alteration of VEGF expression and reproductive failure, including recurrent implantation failure (RIF) and recurrent miscarriage (RM). In order to clarify the role of VEGF in embryo implantation, we reviewed recent literature concerning the expression and function of VEGF in the reproductive system around the time of embryo implantation and we provide a summary of the findings reported so far. We also explored the effects and the possible underlying mechanisms of action of VEGF in embryo implantation.

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“…Moreover, the acute downregulation of luteotropic mediators (progesterone, oxytocin, IGF) and especially the acute changes of HIF1alpha and angiogenic factors (ANPT2 and VEGF) indicate the modulation of vascular stability in luteal tissue, as a key component in the cascade of action important for functional luteolysis after PGF‐induced regression in cow (Berisha et al, 2010, 2017). Nishimura and Okuda (2020) demonstrated the importance of HIF1‐regulated hypoxia in decreasing of progesterone and increasing of apoptosis of luteal cells during luteolysis.…”

Section: Discussionmentioning

confidence: 99%

Regulatory changes of local produced prostaglandins in corpus luteum after experimentally induced luteolysis in the cow

Berisha

Thaqi

Rodler

et al. 2022

Anat Histol Embryol

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The objective of the study was to evaluate the expression patterns of prostaglandin F2alpha (PGF), prostaglandin E2 (PGE), PGF receptor (FP), PGE receptors (EP2 and EP4), prostaglandin‐endoperoxide synthase 2 (PTGS2) and prostaglandin synthases (PGFS and PGES) in corpora lutea (CL) during experimentally induced luteolysis in cow. The Fleckvieh cows in the mid‐luteal phase (days 8–12, control group) were injected with cloprostenol (PGF analogue), and CL were collected by transvaginal ovariectomy before (days 8–12, control group) and at 0.5, 2, 4, 12, 24, 48 and 64 h after PGF application (n = 5 per group). The mRNA expression was determined by RT‐qPCR, the hormone concentrations by enzyme immunoassay and localization by immunohistochemistry. PTGS2 gene expression increased significantly 2 h after PGF application, followed by continuous and significant downregulation afterwards. The PGF tissue concentration increased significantly just after PGF injection and again during structural luteolysis (after 12 h), whereas PGE concentration significantly decreased during structural luteolysis. The FP receptor mRNA decreased significantly at 2 h and again at 12 h after PGF. In contrast, EP4 receptor mRNA increased significantly just after the PGF application (0.5 h). The immunostaining of PGES and PTGS2 on day 15–17 shows numerous positive luteal cells, followed by lower activity afterwards on day 18 (luteolysis). In conclusion, the changes of examined prostaglandin family members in CL tissue after PGF application may be key components of the local mechanisms regulating the cascade of actions leading to functional and subsequent structural luteolysis in the bovine ovary.

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Multiple roles of hypoxia in bovine corpus luteum

Cited by 11 publications

References 50 publications

The involvement of hypoxia-inducible factor 1α (HIF1α)-stabilising factors in steroidogenic acute regulatory (STAR) protein-dependent steroidogenesis in murine KK1 granulosa cells

The involvement of hypoxia-inducible factor 1α (HIF1α)-stabilising factors in steroidogenic acute regulatory (STAR) protein-dependent steroidogenesis in murine KK1 granulosa cells

Role of Vascular Endothelial Growth Factor (VEGF) in Human Embryo Implantation: Clinical Implications

Regulatory changes of local produced prostaglandins in corpus luteum after experimentally induced luteolysis in the cow

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