title: Direct effects of the algal toxin, domoic acid, on ovarian function: Bovine granulosa and theca cells as an in vitro model.
abstract: Domoic acid (DA) is a potent neurotoxin produced by alga Pseudo-nitzschia spp. and has been associated with reproductive disorders in mammals. The aim of this study was to investigate if DA can affect the reproductive system via direct action on ovarian function. Bovine granulosa and theca cells were used as in vitro models for evaluating DA effects on ovarian cell proliferation and steroid production. In small-follicle granulosa cells (SMGC), cell proliferation and estradiol (E2) production was not affected (P>0.05) while progesterone (P4) production was inhibited (P<0.05) by DA at all doses tested. In large-follicle granulosa cells (LGGC), DA had no effect (P>0.05) on cell proliferation or P4 production while E2 production was stimulated by 1 and 5 µg/ml DA (P<0.05). DA (1 µg/ml) attenuated (P<0.05) insulin-like growth factor 1 (IGF-1)-induced P4 production by large-follicle theca cells (LGTC), but did not affect androstenedione (A4) production or proliferation of LGTC. In glutamate-free medium, DA inhibited (P<0.05) SMGC E2 production and this inhibition was similar to inhibition of E2 by trans-(±)-1-amino-1,3-cyclopentanedicarboxylic acid monohydrate (ACPD; a selective metabotropic glutamate receptor subtype agonist) while kainic acid (KA; an ionotropic glutamate receptor subtype agonist) had no effect (P>0.10) on E2 production. Collectively, these results show for the first time that DA has direct effects on ovarian GC and TC steroidogenesis. Because DA inhibited E2 and P4 production, DA has the potential to be an endocrine disruptor.
authors.affiliation: Department of Health, Animal Science and Food Safety, Università degli Studi di Milano, Via Celoria, 10 20133 Milan, Italy.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Pizzo
authors.affiliation: Department of Health, Animal Science and Food Safety, Università degli Studi di Milano, Via Celoria, 10 20133 Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Caloni
authors.affiliation: Department of Animal Science, Oklahoma State University, Stillwater, OK 74078, USA.
authors.forename: Nicole B
authors.initials: NB
authors.lastname: Schreiber
authors.affiliation: Department of Animal Science, Oklahoma State University, Stillwater, OK 74078, USA.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Schutz
authors.affiliation: Department of Animal Science, Oklahoma State University, Stillwater, OK 74078, USA.
authors.forename: Morgan L
authors.initials: ML
authors.lastname: Totty
authors.affiliation: Department of Health, Animal Science and Food Safety, Università degli Studi di Milano, Via Celoria, 10 20133 Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Albonico
authors.affiliation: Department of Animal Science, Oklahoma State University, Stillwater, OK 74078, USA. Electronic address: leon.spicer@okstate.edu.
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Spicer
mesh_terms: D000735:Androstenedione / Q000096:biosynthesis; D000818:Animals; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004958:Estradiol / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists; D005260:Female; D018698:Glutamic Acid; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D006080:Ovarian Follicle; D011374:Progesterone / Q000096:biosynthesis; D013256:Steroids / Q000378:metabolism; D013799:Theca Cells / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018690:Excitatory Amino Acid Agonists; D013256:Steroids; D018698:Glutamic Acid; D000735:Androstenedione; D011374:Progesterone; D004958:Estradiol; C012301:domoic acid; D007608:Kainic Acid
keywords: Cell proliferation; Domoic acid; In vitro effects; Steroidogenesis