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Luteinizing hormone induces ovulation via tumor necrosis factor ?-dependent increases in prostaglandin F2? in a nonmammalian vertebrate.

ABSTRACT: Ovulation is induced by the preovulatory surge of luteinizing hormone (LH) that acts on the ovary and triggers the rupture of the preovulatory ovarian follicle by stimulating proteolysis and apoptosis in the follicle wall, causing the release of the mature oocyte. The pro-inflammatory cytokine tumor necrosis factor ? (TNF?) and prostaglandin (PG) F2? (PGF2?) are involved in the control of ovulation but their role mediating the pro-ovulatory actions of LH is not well established. Here we show that Lh induces PGF2? synthesis through its stimulation of Tnf? production in trout, a primitive teleost fish. Recombinant trout Tnf? (rTnf?) and PGF2? recapitulate the stimulatory in vitro effects of salmon Lh (sLh) on contraction, proteolysis and loss of cell viability in the preovulatory follicle wall and, finally, ovulation. Furthermore, all pro-ovulatory actions of sLh are blocked by inhibition of Tnf? secretion or PG synthesis and all actions of rTnf? are blocked by PG synthesis inhibitors. Therefore, we provide evidence that the Tnf?-dependent increase in PGF2? production is necessary for the pro-ovulatory actions of Lh. The results from this study shed light onto the mechanisms underlying the pro-ovulatory actions of LH in vertebrates and may prove important in clinical assessments of female infertility.

SUBMITTER: Crespo D

PROVIDER: S-EPMC4570979 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Luteinizing hormone induces ovulation via tumor necrosis factor α-dependent increases in prostaglandin F2α in a nonmammalian vertebrate.

Crespo Diego D Goetz Frederick W FW Planas Josep V JV

Scientific reports 20150916

Ovulation is induced by the preovulatory surge of luteinizing hormone (LH) that acts on the ovary and triggers the rupture of the preovulatory ovarian follicle by stimulating proteolysis and apoptosis in the follicle wall, causing the release of the mature oocyte. The pro-inflammatory cytokine tumor necrosis factor α (TNFα) and prostaglandin (PG) F2α (PGF2α) are involved in the control of ovulation but their role mediating the pro-ovulatory actions of LH is not well established. Here we show tha ...[more]

PMID: 26374476

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Project description:Objective:To study the best possible luteinizing hormone (LH) threshold to predict ovulation within the 24, 48, and 72?h. Design:Observational study. Setting:Multicenter collaborative study. Patients:A total of 107 women. Interventions:Women collected daily first morning urine for hormonal assessment and underwent serial ovarian ultrasound. This is a secondary analysis of 283 cycles. Main outcome measures:The sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were estimated for varying ranges of LH thresholds. Receiver operating characteristic curves and cost-benefit ratios were used to estimate the best thresholds to predict ovulation. Results:The best scenario to predict ovulation at random was within 24?h after the first single positive test. The false-positive rate was found to increase as (1) the cycle progressed or (2) two or three consecutive tests were used, or (3) ovulation was predicted within 48 or 72?h. Testing earlier in the cycle increases the predictive value of the test. The ideal thresholds to predict ovulation ranged between 25 and 30?mIU/ml with a PPV (50-60%), NPV (98%), LR+ (20-30), and LR- (0.5). At least, one day with LH ?25?mIU/ml followed by three negatives (LH <25) occurred before ovulation in 31% of all cycles. When used throughout the cycle and evaluated together, peak-fertility type mucus with a positive LH test ?25?mIU/ml provides a higher specificity than either mucus or LH testing alone (97-99 vs. 77-95 vs. 91%, respectively). Conclusion:We identified that beginning LH testing earlier in the cycle (day 7) with a threshold of 25-30?mIU/ml may present the best predictive value for ovulation within 24?h. However, prediction by LH testing alone may be affected negatively by several confounding factors so LH testing alone should not be used to define the end of the fertile window. Complementary markers should be further investigated to predict ovulation and identify the fertile window. The use of the peak cervical mucus along with an LH test may provide a higher specificity and predictive value than either of them alone. We recommend that manufacturers disclose their tests' threshold to the public.

Dataset Information

Luteinizing hormone induces ovulation via tumor necrosis factor ?-dependent increases in prostaglandin F2? in a nonmammalian vertebrate.

Publications

Luteinizing hormone induces ovulation via tumor necrosis factor α-dependent increases in prostaglandin F2α in a nonmammalian vertebrate.

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