Oocyte and cumulus cell cooperativity and metabolic plasticity under the direction of oocyte paracrine factors

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dc.contributor.authorRichani, D.
dc.contributor.authorPoljak, A.
dc.contributor.authorWang, B.
dc.contributor.authorMahbub, S.B.
dc.contributor.authorBiazik, J.
dc.contributor.authorCampbell, J.M.
dc.contributor.authorHabibalahi, A.
dc.contributor.authorStocker, W.A.
dc.contributor.authorMarinova, M.B.
dc.contributor.authorNixon, B.
dc.contributor.authorBustamante, S.
dc.contributor.authorSkerrett-Byrne, D.
dc.contributor.authorHarrison, C.A.
dc.contributor.authorGoldys, E.
dc.contributor.authorGilchrist, R.B.
dc.date.issued2024
dc.description.abstractMammalian oocytes develop and mature in a mutually dependent relationship with surrounding cumulus cells. The oocyte actively regulates cumulus cell differentiation and function by secreting soluble paracrine oocyte-secreted factors (OSFs). We characterized the molecular mechanisms by which two model OSFs, cumulin and BMP15, regulate oocyte maturation and cumulus-oocyte cooperativity. Exposure to these OSFs during mouse oocyte maturation in vitro altered the proteomic and multispectral autofluorescence profiles of both the oocyte and cumulus cells. In oocytes, cumulin significantly upregulated proteins involved in nuclear function. In cumulus cells, both OSFs elicited marked upregulation of a variety of metabolic processes (mostly anabolic), including lipid, nucleotide, and carbohydrate metabolism, whereas mitochondrial metabolic processes were downregulated. The mitochondrial changes were validated by functional assays confirming altered mitochondrial morphology, respiration, and content while maintaining ATP homeostasis. Collectively, these data demonstrate that cumulin and BMP15 remodel cumulus cell metabolism, instructing them to upregulate their anabolic metabolic processes, while routine cellular functions are minimized in the oocyte during maturation, in preparation for ensuing embryonic development. NEW & NOTEWORTHY Oocyte-secreted factors (OSFs) promote oocyte and cumulus cell cooperativity by altering the molecular composition of both cell types. OSFs downregulate protein catabolic processes and upregulate processes associated with DNA binding, translation, and ribosome assembly in oocytes. In cumulus cells, OSFs alter mitochondrial number, morphology, and function, and enhance metabolic plasticity by upregulating anabolic pathways. Hence, the oocyte via OSFs, instructs cumulus cells to increase metabolic processes on its behalf, thereby subduing oocyte metabolism.
dc.description.statementofresponsibilityDulama Richani, Anne Poljak, Baily Wang, Saabah B. Mahbub, Joanna Biazik, Jared M. Campbell, Abbas Habibalahi, William A. Stocker, Maria B. Marinova, Brett Nixon, Sonia Bustamante, David Skerrett-Byrne, Craig A. Harrison, Ewa Goldys, and Robert B. Gilchrist
dc.identifier.citationAmerican Journal of Physiology - Endocrinology and Metabolism, 2024; 326(3):E366-E381
dc.identifier.doi10.1152/AJPENDO.00148.2023
dc.identifier.issn0193-1849
dc.identifier.issn0193-1849
dc.identifier.orcidCampbell, J.M. [0000-0003-0163-4251]
dc.identifier.urihttps://hdl.handle.net/2440/142648
dc.language.isoen
dc.publisherAmerican Physiological Society
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/APP1121504
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/APP1023210
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/APP1117538
dc.rights© 2024 the American Physiological Society.
dc.source.urihttp://dx.doi.org/10.1152/ajpendo.00148.2023
dc.subjectgerm-somatic cell communication; metabolic plasticity; mitochondrial function; oocyte developmental competence; paracrine signaling
dc.subject.meshOocytes
dc.subject.meshAnimals
dc.subject.meshMammals
dc.subject.meshMice
dc.subject.meshProteomics
dc.subject.meshCell Communication
dc.subject.meshEmbryonic Development
dc.subject.meshPregnancy
dc.subject.meshFemale
dc.subject.meshCumulus Cells
dc.subject.meshIn Vitro Oocyte Maturation Techniques
dc.titleOocyte and cumulus cell cooperativity and metabolic plasticity under the direction of oocyte paracrine factors
dc.typeJournal article
pubs.publication-statusPublished

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