Polycystic ovary syndrome: Possible involvement of androgen-induced, chemerin-mediated ovarian recruitment of monocytes/macrophages

Patricia D.A. Lima, Anne Laure Nivet, Qi Wang, Yi An Chen, Arthur Leader, Annie Cheung, Chii Ruey Tzeng, Benjamin K. Tsang

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Polycystic ovary syndrome (PCOS) is a continuum of endocrine and reproductive disorders characterized by hyperandrogenism, antral follicle growth arrest, and chronic inflammation. Macrophages play key role in inflammation, and the balance between M1 (inflammatory) and M2 (anti-inflammatory) macrophages determines physiological/pathological outcomes. Here, we investigated if hyperandrogenism increases ovarian chemerin altering the balance of M1 and M2 macrophages and the granulosa cell death. Ovarian chemerin was upregulated by 5α-dihydrotestosterone (DHT) in lean and overweight rats; while increased serum chemerin levels were only evident in overweight rats, suggesting that the serum chemerin may be reflective of a systemic response and associated with obesity, whereas increased ovarian chemerin expression is a localized response independent of the metabolic status. DHT altered follicle dynamics while increased the M1: M2 macrophages ratio in antral and pre-ovulatory follicles. While ovarian M1 macrophages expressing chemokine-like receptor 1 (CMKLR1) were increased, CMKLR1+ monocytes, which migrated toward chemerin-rich environment, were markedly decreased after 15 days of DHT. Androgen-induced granulosa cell apoptosis was dependent on the presence of macrophages. In humans, chemerin levels in follicular fluid, but not in serum, were higher in lean PCOS patients compared to BMI-matched controls and were associated with increased M1: M2 ratio. Our results support the concept that in PCOS, hyperandrogenemia increases chemerin expression while promotes CMKLR1+ monocytes recruitment and deregulates the immunological niche of ovaries. This study established a new immunological perspective in PCOS at the ovarian level. Hyperandrogenism is associated with upregulation of chemerin and macrophage unbalance in the ovaries.

Original languageEnglish
Pages (from-to)838-852
Number of pages15
JournalBiology of Reproduction
Volume99
Issue number4
DOIs
Publication statusPublished - Oct 1 2018

Fingerprint

Polycystic Ovary Syndrome
Androgens
Monocytes
Macrophages
Hyperandrogenism
Dihydrotestosterone
Chemokine Receptors
Granulosa Cells
Ovary
Serum
Inflammation
Follicular Fluid
Cell Death
Anti-Inflammatory Agents
Up-Regulation
Obesity
Apoptosis
Growth

Keywords

  • androgens
  • chemotaxis
  • female infertility
  • granulosa cells
  • immunology
  • macrophage
  • ovary
  • reproductive immunology

ASJC Scopus subject areas

  • Cell Biology

Cite this

Polycystic ovary syndrome : Possible involvement of androgen-induced, chemerin-mediated ovarian recruitment of monocytes/macrophages. / Lima, Patricia D.A.; Nivet, Anne Laure; Wang, Qi; Chen, Yi An; Leader, Arthur; Cheung, Annie; Tzeng, Chii Ruey; Tsang, Benjamin K.

In: Biology of Reproduction, Vol. 99, No. 4, 01.10.2018, p. 838-852.

Research output: Contribution to journalArticle

Lima, Patricia D.A. ; Nivet, Anne Laure ; Wang, Qi ; Chen, Yi An ; Leader, Arthur ; Cheung, Annie ; Tzeng, Chii Ruey ; Tsang, Benjamin K. / Polycystic ovary syndrome : Possible involvement of androgen-induced, chemerin-mediated ovarian recruitment of monocytes/macrophages. In: Biology of Reproduction. 2018 ; Vol. 99, No. 4. pp. 838-852.
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