Vascular Endothelial Growth Factor (VEGF) Production by the Monkey Corpus Luteum During the Menstrual Cycle: Isoform-Selective Messenger RNA Expression In Vivo and Hypoxia-Regulated Protein Secretion In Vitro1

Tesone, Marta; Stouffer, Richard L.; Borman, Sherri; Hennebold, Jon D.; Molskness, Theodore A.

doi:10.1095/biolreprod.105.039875

Cited by 54 publications

(42 citation statements)

References 50 publications

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“…The ability of the fallopian tube to increase progesterone production is consistent with some clinical studies that suggest that tubal ligation reduces luteal function (Donnez et al, 1980;Corson et al, 1981;Donnez et al, 1981). VEGF-A, secreted from the fallopian tissue in response to ovarian follicles, may contribute to the enhanced corpus luteal P 4 production (Tesone et al, 2005;Qiu et al, 2012). Using this co-culture system, the factors from fallopian tissue that benefit the corpus luteal function can be further explored.…”

Section: Discussionsupporting

confidence: 68%

Human fallopian tube epithelium co-culture with murine ovarian follicles reveals crosstalk in the reproductive cycle

Zhu

Rashedi

et al. 2016

Mol. Hum. Reprod.

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STUDY QUESTION: Do interactions between human fallopian tube epithelium and murine follicles occur during an artificial reproductive cycle in a co-culture system in vitro?SUMMARY ANSWER: In a co-culture system, human fallopian tissues responded to the menstrual cycle mimetic by changes in morphology and levels of secreted factors, and increasing murine corpus luteum progesterone secretion.WHAT IS KNOWN ALREADY: The entire fallopian tube epithelium, including ciliated and secretory cells, can be regulated in the reproductive cycle. Currently, there are no in vitro culture models that can monitor fallopian tissues in real time in response to factors produced by the ovary. In addition, there are no reports on the impact of fallopian tissue on ovarian function during the menstrual cycle.STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Human fallopian tissue (n = 24) was obtained by routine hysterectomies from women (aged 26-50 years, mean age = 43.6) who had not undergone exogenous hormonal treatment for at least 3 months prior to surgery. CD1 female mice were used for ovarian follicle isolation. The human fallopian epithelium layers were either co-cultured with five murine multilayer secondary follicles (150-180 μm follicles, encapsulated in one alginate gel bead) for 15 days or received stepwise steroid hormone additions for 13 days. The fallopian tissue morphology and cilia beating rate, as measured by an Andor Spinning Disk Confocal, were investigated. Oviduct-specific glycoprotein 1 (OVGP1), human insulin-like growth factor 1 (hIGF1), vascular endothelial growth factor A (VEGF-A) and interleukin 8 (IL8) as biological functional markers were measured either by ELISA or western blot to indicate dynamic changes in the fallopian epithelium during the reproductive cycle generated by mouse follicles or by stepwise steroid hormone induction. Three or four patients in each experiment were recruited for replicates. Data were presented as mean ± SD and further analyzed using one-way ANOVA followed by Tukey's multiple comparisons test. MAIN RESULTS AND THE ROLE OF CHANCE:The cultured fallopian tube epithelium responded to exogenous steroid hormone stimulation, as demonstrated by enhanced cilia beating rate (~25% increase, P = 0.04) and an increase in OVGP1 secretion (P = 0.02) in response to 1 nM estradiol (E 2 ) treatment when compared with 0.1 nM E 2 . Conversely, 10 nM progesterone plus 1 nM E 2 suppressed cilia beating rate by~30% (P = 0.008), while OVGP1 secretion was suppressed by 0.1 nM E 2 plus 50 nM progesterone (P = 0.002 versus 1 nM E 2 alone). Human fallopian tube epithelium was co-cultured with murine secondary follicles to mimic the human menstrual cycle. OVGP1 and VEGF-A secretion from fallopian tissue was similar with stepwise hormone treatment and when cultured with murine follicles. However, the secretion patterns of hIGF1 and IL8 differed in the luteal phase when comparing steroid treatment with follicle co-culture. In co-culture, hIGF1 secretion was suppressed in the luteal versus follicular phase (P = 0.005)...

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Section: Discussionsupporting

confidence: 68%

Human fallopian tube epithelium co-culture with murine ovarian follicles reveals crosstalk in the reproductive cycle

Zhu

Rashedi

et al. 2016

Mol. Hum. Reprod.

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“…Hypoxia is therefore an important physiological cue in the developing CL. It is well established that hypoxia plays an important role in the up-regulation of VEGF that occurs at this stage and is responsible for the angiogenic process in early CL (Tesone et al 2005, Nishimura & Okuda 2010, Meidan et al 2013). The current study shows that the hypoxia-mimetic compound elevated HIF1A protein and EDN2 mRNA levels, whereas HIF1A silencing (employed herein for the first time in GCs) reduced EDN2 expression and ablated its response to hypoxia.…”

Section: Discussionmentioning

confidence: 99%

HIF1A-dependent increase in endothelin 2 levels in granulosa cells: role of hypoxia, LH/cAMP, and reactive oxygen species

Yalu¹,

Oyesiji²,

Eisenberg³

et al. 2015

Reproduction

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Hypoxia-inducible factor 1 alpha (HIF1A) and endothelin 2 (EDN2) are transiently expressed during the same time window in the developing corpus luteum (CL). In this study, we sought to investigate the involvement of LH/cAMP, reactive oxygen species (ROS), and a hypoxia-mimetic compound (CoCl 2 ) on HIF1A expression and how it affected EDN2 levels, using transformed human granulosa cells (thGCs) and primary bovine granulosa cells (GCs). CoCl 2 elevated HIF1A protein levels in thGCs in a dose-dependent manner. Forskolin alone had no significant effect; however, forskolin and CoCl 2 together further induced HIF1A protein and EDN2 mRNA expression in thGCs. Similarly, in primary GCs, LH with CoCl 2 synergistically augmented HIF1A protein levels, which resulted in higher expression of EDN2 and another well-known hypoxia-inducible gene, VEGF (VEGFA). Importantly, LH alone elevated HIF1A mRNA but not its protein. The successful knockdown of HIF1A in thGCs using siRNA abolished hypoxia-induced EDN2 and also the additive effect of forskolin and CoCl 2 . We then examined the roles of ROS in thGCs: hydrogen peroxide (20 and 50 mM) elevated HIF1A protein as well as the expression of EDN2, implying that induction of HIF1A protein levels is sufficient to stimulate the expression of EDN2 (and VEGF) in normoxia. A broad-range ROS scavenger, butylated hydroxyanisole, inhibited CoCl 2 -induced HIF1A protein with a concomitant reduction in the mRNA expression of EDN2 and VEGF in thGCs. The results obtained in this study suggest that HIF1A, induced by various stimuli, is an essential mediator of EDN2 mRNA expression. The results may also explain the rise in the levels of HIF1A-dependent genes (EDN2 and VEGF) in the developing CL.

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“…VEGF is considered to be critical in the regulation of normal and abnormal angiogenesis in the ovary (3,9,(13)(14)(15)(16)(17)25,30), particularly in the newly formed corpus luteum. In primates, VEGF protein is localized in the hormone-producing cells of the corpus luteum, and is highest in the granulosa-derived cells (14)(15)(16)(30)(31)(32)(33)(34)(35). VEGF is fundamental in the physiological angiogenesis and vascularization of the follicular luteinizing granulosa layer during corpus luteum formation (15,16,30,32).…”

Section: Discussionmentioning

confidence: 99%

Expression and contribution of the HIF‑1α/VEGF signaling pathway to luteal development and function in pregnant rats

Zhang

Pan

et al. 2015

Mol Med Report

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Abstract. Vascular endothelial growth factor (VEGF) is vital in normal and abnormal angiogenesis in the ovary, particularly during the early development of the corpus luteum in the ovary. However, the molecular regulation of the expression VEGF during luteal development in vivo remains to be fully elucidated. As the expression of VEGF is mediated by hypoxia-inducible factor (HIF)-1α in luteal cells cultured in vitro, determined in our previous study, the present study was performed to confirm the hypothesis that HIF-1α is induced and then regulates the expression of VEGF and VEGF-dependent luteal development/function in vivo. This was investigated using a pregnant rat model treated with a small-molecule inhibitor of HIF-1α, echinomycin (Ech). The development of the corpus luteum in the pregnant rat ovary was identified via performing assays of the serum progesterone, testosterone and estradiol concentrations by radioimmunoassay, accompanied with determination of the changes in the expression levels of HIF-1α and VEGF by reverse transcription-quantitative polymerase chain reaction at different days of the developmental process. On day 5, serum progesterone levels were markedly increased, whereas serum levels of testosterone and estradiol did not change significantly. On day 17, the highest level of serum progesterone was observed, however, this was not the case for testosterone and estradiol. Further analysis of the expression levels of HIF-1α and VEGF revealed that their changes were consistent with the changes in serum levels of progesterone, which occurred in the development of the corpus luteum in the ovaries of pregnant rats. Further investigation demonstrated that Ech inhibited luteal development through inhibiting the expression of VEGF, mediated by HIF-1α, and subsequent luteal function, which was determined by detecting changes in serum progesterone on days 8 and 14. Taken together, these results demonstrated that HIF-1α-mediated expression of VEGF may be one of the important mechanisms regulating ovarian luteal development in mammals in vivo, which may provide novel strategies in treatment for fertility control and for certain types of ovarian dysfunction, including polycystic ovarian syndrome, ovarian hyperstimulation syndrome and ovarian neoplasia.

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Vascular Endothelial Growth Factor (VEGF) Production by the Monkey Corpus Luteum During the Menstrual Cycle: Isoform-Selective Messenger RNA Expression In Vivo and Hypoxia-Regulated Protein Secretion In Vitro1

Cited by 54 publications

References 50 publications

Human fallopian tube epithelium co-culture with murine ovarian follicles reveals crosstalk in the reproductive cycle

Human fallopian tube epithelium co-culture with murine ovarian follicles reveals crosstalk in the reproductive cycle

HIF1A-dependent increase in endothelin 2 levels in granulosa cells: role of hypoxia, LH/cAMP, and reactive oxygen species

Expression and contribution of the HIF‑1α/VEGF signaling pathway to luteal development and function in pregnant rats

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