Abstract
In several species including the buffalo cow, prostaglandin (PG) F2α is the key molecule responsible for regression of corpus luteum (CL). Experiments were carried out to characterize gene expression changes in the CL tissue at various time points after administration of luteolytic dose of PGF2α in buffalo cows. Circulating progesterone levels decreased within 1 h of PGF2α treatment and evidence of apoptosis was demonstrable at 18 h post treatment. Microarray analysis indicated expression changes in several of immediate early genes and transcription factors within 3 h of treatment. Also, changes in expression of genes associated with cell to cell signaling, cytokine signaling, steroidogenesis, PG synthesis and apoptosis were observed. Analysis of various components of LH/CGR signaling in CL tissues indicated decreased LH/CGR protein expression, pCREB levels and PKA activity post PGF2α treatment. The novel finding of this study is the down regulation of CYP19A1 gene expression accompanied by decrease in expression of E2 receptors and circulating and intra luteal E2 post PGF2α treatment. Mining of microarray data revealed several differentially expressed E2 responsive genes. Since CYP19A1 gene expression is low in the bovine CL, mining of microarray data of PGF2α-treated macaques, the species with high luteal CYP19A1 expression, showed good correlation between differentially expressed E2 responsive genes between both the species. Taken together, the results of this study suggest that PGF2α interferes with luteotrophic signaling, impairs intra-luteal E2 levels and regulates various signaling pathways before the effects on structural luteolysis are manifest.
Highlights
Corpus luteum (CL) is a transient endocrine structure formed from the remnants of the ovulating follicle
Analysis of low molecular weight DNA fragments indicated that a slight increase in low molecular weight fragments could be visualized in CL tissues at 6 h post PGF2a treatment compared to untreated CL tissue, but a clear increase of laddering pattern of DNA was observed in CL tissues collected from animals, 18 h post PGF2a treatment (Figure S2C)
These results verified that CL tissue underwent a time related rapid functional loss followed by evidence of structural loss after initiation of PGF2a treatment
Summary
Corpus luteum (CL) is a transient endocrine structure formed from the remnants of the ovulating follicle. Through secretion of progesterone (P4), it plays a pivotal role in the control of reproduction in mammals. During non-pregnant cycles, regression of CL precedes initiation of new reproductive cycle to allow reovulation and another chance for conception to occur [1]. The structure and function of CL are controlled by intricate interplay between luteotrophic and luteolytic factors. In several species including bovines, the influence of lytic factors dominate over luteotropic factors in the control of luteal function. Prostaglandin (PG) F2a molecule is recognized as the physiological luteolysin responsible for luteal regression in mammals [2,3,4]
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