Subfertility and reduced progestin synthesis in Pgrmc2 knockout zebrafish

Area of Science:

• Reproductive Biology
• Molecular Endocrinology
• Zebrafish Models

Background:

• Progestin receptor membrane component 1 (Pgrmc1) is a heme-binding protein implicated in steroidogenesis and protein transfer.
• The physiological roles of its paralog, Progestin receptor membrane component 2 (Pgrmc2), remain largely unexplored.

Purpose of the Study:

• To investigate the function of Pgrmc2 in female fertility and oocyte maturation using a zebrafish model.
• To elucidate the molecular mechanisms underlying Pgrmc2's role in reproductive processes.

Main Methods:

• Generation and analysis of a zebrafish pgrmc2 knockout mutant line (pgrmc2^-/-).
• Assessment of reproductive parameters including spawning frequency and embryo production.
• Evaluation of oocyte maturation in vivo and in vitro.
• Quantitative analysis of gene and hormone expression in ovaries.

Main Results:

• Female pgrmc2^-/- zebrafish exhibit reduced spawning and embryo production, indicative of subfertility.
• Oocyte maturation (germinal vesicle breakdown) is impaired in pgrmc2^-/- zebrafish in vivo.
• Expression of key hormones, receptors (lhcgr, egfra, ar, esr2), and steroidogenic enzymes (cyp11a1, hsd3b1) is significantly decreased in pgrmc2^-/- ovaries.
• Ovarian levels of 17α,20β-dihydroxy-4-pregnen-3-one (DHP) are significantly lower in pgrmc2^-/- compared to wildtype.

Conclusions:

• Pgrmc2 plays a crucial role in regulating female fertility and oocyte maturation in zebrafish.
• The subfertility phenotype is associated with impaired steroidogenesis and altered expression of reproductive hormone signaling pathways.
• Pgrmc2 likely functions by modulating ovarian steroid and receptor levels, thereby influencing oocyte maturation.