Metabolomic-based analysis reveals bile acid-mediated ovarian failure induced by low temperature in zebrafish

Abstract

As ectotherms, fish are highly sensitive to temperature fluctuations, which can profoundly impact their reproductive cycles. In this study, we investigated the fertility and histological characteristics of zebrafish ( Danio rerio) ovaries exposed to a temperature gradient ranging from the thermopreferendum temperature of the species, 27°C, to lower temperatures of 22°C, 20°C, and 13°C over a period of two weeks. Comparative metabolomic (six biological replicates for each temperature) and transcriptomic (four biological replicates for each temperature) analyses were conducted under the four temperature conditions. Results indicated that lower temperatures inhibited oocyte development and differential metabolites were involved in steroid hormone production, antioxidant function, and lipid and protein catabolism. Disrupted reproductive hormones, increased proteolysis, and lipid degradation significantly impeded oocyte development and egg maturation. Notably, a significant increase in bile acid content was noted in the ovaries of the cold-treated fish, indicating that bile acids play a critical role in ovarian failure. Overall, these findings provide valuable insights into the mechanisms governing the reproductive response of fish to cold stress.

Keywords: Cold stress; Metabolome; Ovarian failure; Zebrafish.

Figure 1

Morphology of ovaries and eggs in zebrafish acclimated to different cold temperatures

Figure 2

Metabolite screening

Figure 3

Cluster analysis of metabolites

Figure 4

Intermediate product of estradiol synthesis and up-regulated PGs

Figure 5

Down-regulated antioxidants, up-regulated amino acids, LPUFAs, and Pearson correlation analysis

Figure 6

Substances involved in bile acid formation at low temperature

Figure 7

Comparation between control and GDCA-treated groups

Figure 8

Model diagram of ovarian abortion in zebrafish induced by low temperature