Mapping molluscan endocrinology: a systematic and critical appraisal

TL;DR

This paper reviews molluscan endocrinology, highlighting gaps in research and the need for better experimental methods.

Contribution

The study provides a systematic review and critical appraisal of molluscan hormone research, revealing significant methodological shortcomings and research biases.

Findings

95% of studies did not test if hormones bind to their receptors.

83% of studies lacked independent experimental repetition.

Most research focused on vertebrate-type steroids despite weak evidence of their biosynthesis in molluscs.

Abstract

Historically, a vertebrate‐centric paradigm has framed our interpretation of molluscan endocrinology, with considerable research focusing on vertebrate‐type steroid hormones (e.g. oestrogens, testosterone). However, contradictory evidence on the occurrence of vertebrate‐type steroid hormones in molluscan tissues, and a lack of the specific steroidogenesis enzymes involved in producing these steroids has fuelled an ongoing debate about the ability of molluscs to biosynthesise vertebrate‐type steroids de novo. Consequently, the exploration of other hormonal pathways that may exist in the phylum remains a significant knowledge gap. This study systematically identified, combined and evaluated evidence from 147 eligible studies (published between 2012 and 2021) on the occurrence of hormones, hormone receptors and hormone‐metabolising enzymes in Mollusca according to the 2015 PRISMA‐P systematic review guidelines and the 2020 COSTER guidelines. The data collected are holistically summarised and visualised in a fully searchable, interactive and openly accessible online database using Tableau Public 2023.1 software. A critical appraisal assessment (Risk‐of‐Bias tool) accompanied by tailor‐made guidelines as well as a narrative synthesis using comparative endocrinology is presented. Strikingly, 95% of studies measuring hormones in molluscs did not investigate the hormones' ability to bind to their respective receptors. Moreover, many studies either used methods now considered unreliable (e.g. lack specificity) to identify relevant biomolecules (i.e. hormones, receptors, enzymes) or did not employ robust internal validation steps, with 83% of all studies not independently repeating their experiments. This highlights an urgent need for greater experimental rigour in the field. Most studies were also found to be heavily skewed towards vertebrate‐type sex steroidogenesis, with 66% measuring 17β‐oestradiol in mollusc tissues, despite unconvincing evidence that molluscs can biosynthesise vertebrate‐type steroids. By contrast, the retinoic acid signalling pathway, known to be more evolutionarily conserved (and a target of environmental pollution), has received far less attention. However, a limited number of studies are now looking beyond vertebrate‐type sex steroids, notably those looking at thyroid hormones, phytosterols (plant sterols) and ecdysteroids (insect steroids) in molluscs. These studies should act as a catalyst to spark interest in further exploration of understudied or unexplored hormonal pathways in Mollusca to elucidate fully the endocrinology of this important phylum.

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