Involvement of chemerin and CMKLR1 in the progesterone decrease by PCOS granulosa cells.

Area of Science:

• Reproductive Endocrinology
• Molecular Endocrinology
• Steroidogenesis

Background:

• Polycystic ovary syndrome (PCOS) is a leading cause of female infertility.
• PCOS is associated with impaired progesterone production by human luteinized granulosa cells (hlGCs).
• The molecular mechanisms underlying steroidogenesis dysfunction in PCOS remain unclear.

Purpose of the Study:

• To investigate the role of chemerin and its receptor CMKLR1 in altered progesterone production in PCOS.
• To explore the expression and function of chemerin/CMKLR1 in granulosa cells from PCOS patients.

Main Methods:

• Quantification of progesterone and chemerin levels in plasma and follicular fluid.
• Measurement of STAR mRNA expression in human luteinized granulosa cells (hlGCs).
• In vitro studies using hlGCs treated with chemerin and a CMKLR1-targeting nanobody (VHH CA4910).

Main Results:

• PCOS patients exhibited significantly lower plasma and follicular fluid progesterone levels.
• Higher chemerin, RARRES2, and CMKLR1 mRNA levels were observed in PCOS hlGCs.
• CMKLR1 inactivation with VHH CA4910 blocked chemerin-induced progesterone inhibition; chemerin's inhibitory effect was amplified in PCOS hlGCs.

Conclusions:

• Chemerin, acting through CMKLR1, is implicated in the steroidogenesis alterations observed in PCOS.
• CMKLR1 signaling may represent a therapeutic target for managing infertility associated with PCOS.