Transition Metal Chelator Induces Progesterone Production in Mouse Cumulus-Oocyte Complexes and Corpora Lutea

Area of Science:

• Reproductive biology
• Endocrinology
• Cellular signaling

Background:

• Progesterone production in granulosa cells increases post-LH surge, but regulatory mechanisms remain unclear.
• Transition metal chelator TPEN has been shown to impair ovarian function.
• Understanding intra-follicular regulation of progesterone is key for reproductive health.

Purpose of the Study:

• To investigate the role of transition metals, specifically zinc, in regulating progesterone production.
• To explore the effects of the transition metal chelator TPEN on ovarian steroidogenesis.
• To elucidate the impact of altered progesterone levels on oocyte developmental potential.

Main Methods:

• Culture of cumulus-oocyte complexes (COC) and luteal tissue with TPEN.
• Dietary zinc deficiency in animal models.
• Quantification of steroidogenic gene mRNA (Cyp11a1, Star, Hsd3b) and protein (STAR).
• Measurement of progesterone production and assessment of oocyte developmental potential (blastocyst formation).
• Inhibition of SMAD2/3 signaling pathway.

Main Results:

• TPEN treatment significantly increased Cyp11a1 and Star mRNA (8-20 fold) and progesterone production (>3 fold) in cultured COC.
• Zinc deficiency for 10 days increased Star, Hsd3b, and Ptgfr mRNA, suggesting TPEN's effect is mediated by zinc availability.
• Progesterone supplementation restored blastocyst formation rates in maturation-blocked oocytes.
• TPEN treatment of luteal tissue also enhanced steroidogenic gene expression and progesterone production.
• TPEN abolished SMAD2/3 signaling, but SMAD2/3 inhibition alone did not induce steroidogenesis.

Conclusions:

• Depletion of transition metals, particularly zinc, acutely enhances progesterone biosynthesis in both cumulus-oocyte complexes and luteal tissue.
• Modulating transition metal availability offers a novel strategy to enhance progesterone production for improved oocyte developmental potential.
• The findings highlight the critical role of transition metals in ovarian steroidogenesis and reproductive function.