Vitamin K (VK) is a fat-soluble vitamin that vertebrates have to acquire from the diet, since they are not able to de novo synthesize it. VK has been historically known to be required for the control of blood coagulation, and more recently, bone development and homeostasis. Our understanding of the VK metabolism and the VK-related molecular pathways has been also increased, and the two main VK-related pathways—the pregnane X receptor (PXR) transactivation and the co-factor role on the γ-glutamyl carboxylation of the VK dependent proteins—have been thoroughly investigated during the last decades. Although several studies evidenced how VK may have a broader VK biological function than previously thought, including the reproduction, little is known about the specific molecular pathways. In vertebrates, sex differentiation and gametogenesis are tightly regulated processes through a highly complex molecular, cellular and tissue crosstalk. Here, VK metabolism and related pathways, as well as how gametogenesis might be impacted by VK nutritional status, will be reviewed. Critical knowledge gaps and future perspectives on how the different VK-related pathways come into play on vertebrate’s reproduction will be identified and proposed. The present review will pave the research progress to warrant a successful reproductive status through VK nutritional interventions as well as towards the establishment of reliable biomarkers for determining proper nutritional VK status in vertebrates.
Vitamin K (VK) is a key nutrient for several biological processes (e.g., blood clotting and bone metabolism). To fulfill VK nutritional requirements, VK action as an activator of pregnane X receptor (Pxr) signaling pathway, and as a co-factor of γ-glutamyl carboxylase enzyme, should be considered. In this regard, VK recycling through vitamin K epoxide reductases (Vkors) is essential and should be better understood. Here, the expression patterns of vitamin K epoxide reductase complex subunit 1 (vkorc1) and vkorc1 like 1 (vkorc1l1) were determined during the larval ontogeny of Senegalese sole (Solea senegalensis), and in early juveniles cultured under different physiological conditions. Full-length transcripts for ssvkorc1 and ssvkorc1l1 were determined and peptide sequences were found to be evolutionarily conserved. During larval development, expression of ssvkorc1 showed a slight increase during absence or low feed intake. Expression of ssvkorc1l1 continuously decreased until 24 h post-fertilization, and remained constant afterwards. Both ssvkors were ubiquitously expressed in adult tissues, and highest expression was found in liver for ssvkorc1, and ovary and brain for ssvkorc1l1. Expression of ssvkorc1 and ssvkorc1l1 was differentially regulated under physiological conditions related to fasting and re-feeding, but also under VK dietary supplementation and induced deficiency. The present work provides new and basic molecular clues evidencing how VK metabolism in marine fish is sensitive to nutritional and environmental conditions.
Rising global temperatures threaten species with environmental sex determination by skewing population sex ratios. However, predictions of demographic collapse often overlook the potential for multigenerational adaptation mechanisms. Here, we investigated the transgenerational impacts of elevated temperature on sex ratios and reproductive physiology in the European sea bass ( Dicentrarchus labrax ), a modern teleost with a polygenic sex determination system highly sensitive to temperature. Over more than a decade and using > 3000 fish, we reared three successive generations (F0–F2) under control or elevated temperatures. In this study, we report detailed data from ~1500 juveniles of the F2 generation distributed across eight groups with unique thermal histories. Direct developmental exposure consistently induced masculinization, but we uncovered a novel compensatory parental effect. The influence of ancestral thermal exposure did not follow a simple cumulative pattern. Instead, its direction depends on the line's inherent sex tendency. Paternal lines with baseline sex biases produced offspring with a sex ratio skewed in the opposite direction when exposed to elevated temperatures. This significant plasticity suggests a potential adaptive mechanism that may counteract extreme demographic imbalances. Gonad histological analysis further revealed a significant delay in spermatogenesis in heat‐exposed males at one year, whereas female gonadal development and chemical composition were unaffected by temperature. Our findings demonstrate that predicting the impacts of climate change requires a multigenerational perspective. Transgenerational plasticity can generate complex compensatory responses that may enhance demographic resilience, whereas genetic variability among lines can modulate these effects on sex ratios. Whether this phenomenon is unique to sea bass or widespread among other temperature‐sensitive species remains to be determined. By integrating ancestral thermal exposure into eco‐evolutionary models, our results expand the discussion on population responses to global warming, and highlight the need for comparable multigenerational studies across taxa.