Abstract
Recent studies have shown hypoxia to be an endocrine disruptor that impairs sex differentiation and reproductive function, leading to male-biased F1 populations in fish. However, the molecular mechanisms through which hypoxia alters fish sex differentiation and therefore sex ratios remain poorly understood. In order to understand the potential role of miRNAs in mediating hypoxia-altered sex determination and differentiation in fish, we conducted small RNA sequencing and transcriptome sequencing on marine medaka (Oryzias melastigma) embryos that were exposed to hypoxia (2.0 ± 0.2 mg O2 L–1) for 40 h (encompassing a critical window of sex determination). We identified dysregulated miRNAs and mRNAs in the hypoxia-exposed embryo, and bioinformatic analysis of the integrative small RNA sequencing and transcriptome sequencing results revealed hypoxia to cause alterations of genes related to embryonic development through miRNA regulation. Importantly, we have identified miRNA-mRNA pairs that were reported to play roles in gonad development (novel miR-145-col9a3 and novel miRNA-94- arid5b), in sex hormone response (novel miRNA-210-ca2, novel miRNA-106-nr2f2, nbr-miR-29c-nr4a1, and ola-miR-92b-akr1d1), and in sex characteristic development (novel miRNA-145-mns1, nle-miR-20-sord, and ipu-miR-219b-abcc8). Our findings highlighted the possible roles of miRNA–mRNA in regulation of embryonic development and sex determination in response to hypoxic stress.
Highlights
Hypoxia is a widespread and pressing environmental concern in aquatic habitats, causing severe habitat damage and major disruption to aquatic ecosystems worldwide
Using marine medaka embryos as a model, together with integrative omics analysis, including small-RNA sequencing and transcriptome sequencing, we investigated the role of specific hypoxia-responsive miRNAs in directly targeting sex determination genes
We identified miRNA-mRNA pairs that may be involved in biological functions related to sex determination and differentiation including novel miR-145-col9a3 and novel miRNA-94- arid5b in gonad development, novel miRNA210-ca2, novel miRNA-106-nr2f2, nbr-miR-29c-nr4a1, and ola-miR-92b-akr1d1 in sex hormone response, and novel miRNA-145-mns1, nle-miR-20-sord, and ipu-miR-219b-abcc8 in sex characteristic development (Figure 3C)
Summary
Hypoxia is a widespread and pressing environmental concern in aquatic habitats, causing severe habitat damage and major disruption to aquatic ecosystems worldwide. Previous studies from our group have shown that hypoxia is an endocrine disruptor that impairs reproductive activities and affects sexual differentiation in fish, leading to male-biased F1 generations (Shang et al, 2006; Cheung et al, 2014). A largescale field study from the Gulf of Mexico, one of the largest hypoxic dead zones in the world, reported similar endocrine disruption phenomena − extensive reproductive disruption, ovarian masculinization and male-biased Atlantic croaker sex ratios − occurring in natural fish populations (Thomas and Rahman, 2012). Distinct subsets of miRNAs have been observed in both male and female Nile tilapia embryos (Eshel et al, 2014) and gonads (Wang et al, 2016), indicating potential regulatory roles for miRNAs in the sexual differentiation of fish. The abovementioned studies strongly implicate miRNAs as a new and important class of effector molecules controlling gonadal development and sexual differentiation in vertebrates
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