Leukemia inhibitory factor is necessary for ovulation in female rhesus macaques

Melinda J. Murphy, Nathan G. Halow, Pamela A. Royer, Jon Hennebold

    Research output: Contribution to journalArticle

    7 Citations (Scopus)

    Abstract

    Although the requirement of pituitary-derived LH for ovulation is well documented, the intrafollicular paracrine and autocrine processes elicited by LH necessary for follicle rupture are not fully understood. Evaluating a published rhesus macaque periovulatory transcriptome database revealed thatmRNAencoding leukemia inhibitory factor (LIF) and its downstream signaling effectors are up-regulated in the follicle after animals receive an ovulatory stimulus (human chorionic gonadotropin [hCG]). Follicular LIF mRNA and protein levels are below the limit of detection before the administration of hCG but increase significantly 12 hours thereafter. Downstream LIF receptor (LIFR) signaling components including IL-6 signal transducer, the receptor associated Janus kinase 1, and the transcription factor signal transducer and activator of transcription 3 also exhibit increased expression in the rhesus macaque follicle 12 hours after administration of an ovulatoryhCG bolus. A laparoscopic ovarian evaluation 72 hours after the injection of a LIF antagonist (soluble LIFR) into the rhesus macaque preovulatory follicle and hCG administration revealed blocking LIF action prevented ovulation (typically occurs 36-44 h after hCG). Moreover, ovaries removed 52 hours after both hCG and intrafollicular soluble LIFR administration confirmed ovulation was blocked asevidencedbythepresenceofanintact follicleandatrappedcumulus-oocytecomplex.Thesefindings give new insight into the role of LIF in the primate ovary and could lead to the development of new approaches for the control of fertility.

    Original languageEnglish (US)
    Pages (from-to)4378-4387
    Number of pages10
    JournalEndocrinology
    Volume157
    Issue number11
    DOIs
    StatePublished - Nov 1 2016

    Fingerprint

    Leukemia Inhibitory Factor
    Chorionic Gonadotropin
    Ovulation
    Macaca mulatta
    OSM-LIF Receptors
    Ovary
    Janus Kinase 1
    STAT3 Transcription Factor
    Transducers
    Contraception
    Transcriptome
    Primates
    Limit of Detection
    Rupture
    Interleukin-6
    Transcription Factors
    Databases
    Messenger RNA
    Injections
    Proteins

    ASJC Scopus subject areas

    • Endocrinology

    Cite this

    Leukemia inhibitory factor is necessary for ovulation in female rhesus macaques. / Murphy, Melinda J.; Halow, Nathan G.; Royer, Pamela A.; Hennebold, Jon.

    In: Endocrinology, Vol. 157, No. 11, 01.11.2016, p. 4378-4387.

    Research output: Contribution to journalArticle

    Murphy, Melinda J. ; Halow, Nathan G. ; Royer, Pamela A. ; Hennebold, Jon. / Leukemia inhibitory factor is necessary for ovulation in female rhesus macaques. In: Endocrinology. 2016 ; Vol. 157, No. 11. pp. 4378-4387.
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    abstract = "Although the requirement of pituitary-derived LH for ovulation is well documented, the intrafollicular paracrine and autocrine processes elicited by LH necessary for follicle rupture are not fully understood. Evaluating a published rhesus macaque periovulatory transcriptome database revealed thatmRNAencoding leukemia inhibitory factor (LIF) and its downstream signaling effectors are up-regulated in the follicle after animals receive an ovulatory stimulus (human chorionic gonadotropin [hCG]). Follicular LIF mRNA and protein levels are below the limit of detection before the administration of hCG but increase significantly 12 hours thereafter. Downstream LIF receptor (LIFR) signaling components including IL-6 signal transducer, the receptor associated Janus kinase 1, and the transcription factor signal transducer and activator of transcription 3 also exhibit increased expression in the rhesus macaque follicle 12 hours after administration of an ovulatoryhCG bolus. A laparoscopic ovarian evaluation 72 hours after the injection of a LIF antagonist (soluble LIFR) into the rhesus macaque preovulatory follicle and hCG administration revealed blocking LIF action prevented ovulation (typically occurs 36-44 h after hCG). Moreover, ovaries removed 52 hours after both hCG and intrafollicular soluble LIFR administration confirmed ovulation was blocked asevidencedbythepresenceofanintact follicleandatrappedcumulus-oocytecomplex.Thesefindings give new insight into the role of LIF in the primate ovary and could lead to the development of new approaches for the control of fertility.",
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