Changes in MicroRNA Expression During Maturation of the Bovine Corpus Luteum: Regulation of Luteal Cell Proliferation and Function by MicroRNA-34a.

Biol Reprod

Department of Animal Science, Center for Reproductive Biology and Health, The Pennsylvania State University, University Park, Pennsylvania

Published: March 2016

AI Article Synopsis

  • The corpus luteum (CL) is crucial for maintaining pregnancy in mammals by producing progesterone, and its development involves the transformation of granulosal and thecal cells into luteal cells.
  • As the CL matures, it can regress in response to prostaglandin F2alpha, but the regulatory mechanisms of this process are not well understood.
  • This study aimed to analyze the expression of microRNAs (miRNAs) in developing versus mature bovine CL and found that specific miRNAs play roles in luteal cell survival, function, and the transition from a growth phase to a maintenance phase.

Article Abstract

The corpus luteum (CL) develops from the remnants of the ovulatory follicle and produces progesterone, required for maintenance of pregnancy in mammals. The differentiation of granulosal and thecal cells into luteal cells is accompanied by hypertrophy and hyperplasia of cells. As the CL matures, growth ceases and in ruminants, the tissue acquires the ability to undergo regression in response to prostaglandin F2alpha. The regulators of this transition are poorly understood. MicroRNA, which are posttranscriptional regulators of tissue development and function, are expressed in the CL. However, the pattern of their expression and their function during the transition from developing to functional CL is not known. The objectives of this study were to profile the expression of miRNA in developing versus mature bovine CL and determine effects of miRNA on bovine luteal cell survival and function. Knockdown of Drosha in midcycle (MC) luteal cells decreased progesterone and increased luteal cell apoptosis in the presence or absence of proinflammatory cytokines. Microarray analysis demonstrated that a greater number of miRNA were expressed in MC compared to D4 CL. Ingenuity pathway analysis (IPA) predicted that D4-specific miRNA regulate pathways related to carbohydrate metabolism, while MC-specific miRNA regulate pathways related to cell cycle and apoptosis signaling. Both predictions are consistent with a switch in the CL from a growing phase to a maintenance phase. One of the MC specific miRNA, miR-34a, was selected for further analysis. Increased concentrations of miR-34a in MC luteal cells resulted in decreased luteal cell proliferation, increased progesterone production, and inhibition of Notch1 and YY1 translation, but had no effect on luteal cell apoptosis. In conclusion, these data support a role for miRNA in general, and miR-34a in particular, in luteal formation and function.

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Source
http://dx.doi.org/10.1095/biolreprod.115.135053DOI Listing

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