Experimental polycystic ovarian syndrome is associated with reduced expression and function of P2Y2 receptors in rat

Anaí Del Rocío Campos-Contreras1, Ana Patricia Juárez-Mercado1, Adriana González-Gallardo2

  • 1Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Juriquilla Querétaro, México.

Insights

Polycystic ovary syndrome (PCOS) disrupts ovarian function by altering purinergic signaling. P2Y2 receptor activity, crucial for theca cell proliferation in healthy ovaries, is reduced in PCOS, leading to lost control over cell growth.

Area of Science:

  • Endocrinology
  • Reproductive Biology
  • Cell Signaling

Background:

  • Extracellular purines, acting via specific receptors, are emerging regulators of ovarian function.
  • P2Y2 receptor activity is known to stimulate theca cell proliferation.

Purpose of the Study:

  • To investigate the role of purinergic signaling in polycystic ovary syndrome (PCOS) by analyzing UTP-sensitive P2Y receptors in theca cells (TC).
  • To determine the impact of experimentally-induced PCOS (EI-PCOS) on P2Y receptor expression and TC proliferation.

Main Methods:

  • Polymerase chain reaction (PCR) to detect P2Y receptor transcripts in rat TC.
  • Assessment of extracellular signal-regulated kinases (ERK) phosphorylation in response to UTP.
  • Analysis of TC proliferation in control and EI-PCOS rat models.
  • In silico promoter analysis of P2yr2 and testosterone stimulation experiments.

Main Results:

  • All P2Y receptor transcripts were detected in normal rat TC; UTP induced ERK phosphorylation.
  • EI-PCOS rats exhibited reduced P2Y2 receptor (P2Y2R) expression in TC, while P2Y4R expression remained unchanged.
  • UTP stimulated TC proliferation in control rats but not in EI-PCOS rats, indicating P2Y2R's role.
  • Testosterone significantly reduced P2yr2 transcript expression in TC.

Conclusions:

  • P2Y2R is the primary P2Y receptor mediating UTP-induced proliferation in rat TC.
  • The regulatory role of P2Y2R in TC proliferation is impaired in the context of EI-PCOS.
  • Androgenic influence, via response elements in the P2yr2 promoter, contributes to the altered P2Y2R expression in PCOS.

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