Here, we have adhered to the RepOrting standards for Systematic Evidence Syntheses for systematic map protocols in environmental research (ROSES) [26] (shown in Additional file 1: Appendix S1).
For our Map of Systematic Reviews, we will also report our systematic search and literature selection following (ROSES) [26]. See Fig. 2 for a 'workflow' diagram.
Searching for articles
We will search three broad-coverage databases—Scopus, ISI Web of Science Core Collection, and PubMed for SRs. The searches will be performed using a custom-designed search string made of three groups of English-language keywords: (1) related to non-genetic inheritance (e.g., maternal, paternal, non-genetic inheritance, inter-generation, trans-generation), (2) related to SR type (e.g., systematic review with or without meta-analysis), and (3) exclusion keywords filtering out most human-centered articles (e.g., men, women, person, worker, patient) as a majority of these studies are purely correlational and we are focussing on SRs that synthesise direct manipulations of the environment (most biomedical studies are experimental studies on rodents). In the search string, we will use database-specific wildcard symbols to include word variants, and Boolean and proximity operators to build efficient and sensitive search strings. We will not use language filters, so we can capture relevant literature published in languages other than English indexed with English-language keywords, titles or abstracts. We will then include studies in languages that we are able to understand (English, Japanese, Polish, Russian). We acknowledge that this may create a language bias, and this will be mentioned in our map of systematic reviews.
We will use the following search string. This search string has been validated through piloting (on Scopus and Web of Science), including literature screening, and a benchmark set of 9 papers (see Additional file 2: Appendix S2).
Scopus search string: (TITLE-ABS-KEY (“silver spoon” OR “epigenetic inheritance” OR “non-genetic inheritance” OR “nongenetic inheritance” OR “extended inheritance” OR “extended heritability” OR “developmental programming” OR “developmental* program*” OR “DOHAD” OR *maternal* OR *paternal* OR *parental* OR trans-generation* OR multi-generation* OR inter-generation* OR across-generation* OR between-generation* OR transgeneration* OR multigeneration* OR intergeneration* OR epigenet*) AND (TITLE-ABS-KEY (meta-analy* OR metaanaly* OR meta-regress* OR metaregress*) OR TITLE-ABS-KEY ((systematic* OR comprehensiv* OR rapid OR scoping OR quantitativ* OR evidence) W/5 (review* OR map* OR synthes*))) AND NOT TITLE-ABS-KEY (sport* OR econom* OR business* OR software* OR dent* OR orthodont* OR healthcare* OR patient* OR guideline* OR job* OR worker* OR veteran* OR school* OR student* OR child* OR infant* OR baby OR woman OR women OR breast* OR obstetr* OR eclampsia OR family OR placebo OR cancer OR violen* OR hospital* OR diagnos* OR autis* OR educat* OR countries OR china OR africa OR cohort* OR longit* OR rct OR qtl OR gwas OR genome-wide OR age* OR aging OR polyandr* OR chromosom* OR allel* OR genom* OR mutant OR polymorphism OR lifestyle OR leadership OR survey OR comment* OR corrigendum OR erratum)).
Web of Science search string: TS=((“silver spoon” OR “epigenetic inheritance” OR “non-genetic inheritance” OR “nongenetic inheritance” OR “extended inheritance” OR “extended heritability” OR “developmental programming” OR “developmental* program*” OR “DOHAD” OR *maternal* OR *paternal* OR *parental* OR trans-generation* OR multi-generation* OR inter-generation* OR across-generation* OR between-generation* OR transgeneration* OR multigeneration* OR intergeneration* OR epigenet*) AND ((meta-analy* OR metaanaly* OR meta-regress* OR metaregress* OR evidence) OR (systematic* OR comprehensiv* OR rapid OR scoping OR quantitativ*) NEAR/5 (review* OR map* OR synthes*)) NOT (sport* OR econom* OR business* OR software* OR dent* OR orthodont* OR healthcare* OR patient* OR guideline* OR job* OR worker* OR veteran* OR school* OR student* OR child* OR infant* OR baby OR woman OR women OR breast* OR obstetr* OR eclampsia OR family OR placebo OR cancer OR violen* OR hospital* OR diagnos* OR autis* OR educat* OR countries OR china OR africa OR cohort* OR longit* OR rct OR qtl OR gwas OR genome-wide OR age* OR aging OR polyandr* OR chromosom* OR allel* OR genom* OR mutant OR polymorphism OR lifestyle OR leadership OR survey OR comment* OR corrigendum OR erratum)).
PubMed search string: ("silver spoon"[Title/Abstract]) OR ("epigenetic inheritance"[Title/Abstract]) OR ("non-genetic inheritance"[Title/Abstract]) OR ("nongenetic inheritance"[Title/Abstract]) OR ("extended inheritance"[Title/Abstract]) OR ("extended heritability"[Title/Abstract]) OR ("developmental* program*"[Title/Abstract]) OR (DOHAD[Title/Abstract]) OR (*maternal*[Title/Abstract]) OR (*paternal*[Title/Abstract]) OR (*parental*[Title/Abstract]) OR (trans-generation*[Title/Abstract]) OR (multi-generation*[Title/Abstract]) OR (inter-generation*[Title/Abstract]) OR (across-generation*[Title/Abstract]) OR (between-generation*[Title/Abstract]) OR (transgeneration*[Title/Abstract]) OR (multigeneration*[Title/Abstract]) OR (intergeneration*[Title/Abstract]) OR (epigenet* [Title/Abstract]) Filters: Meta-Analysis, Systematic Review, Other Animals.
This search string resulted in 652 hits on Scopus, 816 hits on Web of Science, 280 hits on PubMed and captures all 9 of our preselected benchmark papers (i.e., a validation set used to assess sensitivity of our search and benchmark papers (test set) which are listed in Additional file 2: Appendix S2). Through a pilot literature screening (see Additional file 2: Appendix S2), we estimated that we could get between 50 and 100 relevant full texts for inclusion in our map of SRs, from all planned search sources. Note that we do not include the search term “literature review” as we are not including non-systematic narrative reviews (see “Definition of systematic reviews” below) and the inclusion of this term substantially increases the number of irrelevant search hits in our literature search.
Apart of using direct searches of online literature databases, we will also conduct backwards and forwards searching for additional SRs that may not have been already picked up. These ‘snowballing’ searches will start from the set of papers included after screening of the above-mentioned online databases. Using Scopus, we will create a custom list of cited and citing papers. We will then pre-filter this list using exact keywords related to review type and screen the remaining references for inclusion in our map, following the same procedure as for the references from the main database searches.
We will also search academic grey literature (Ph.D., Masters and Honours theses) using Bielefeld Academic Search Engine (BASE), with doctype:18* (used for theses) and combinations of English keywords related to non-genetic inheritance (e.g., maternal, paternal, non-genetic inheritance, inter-generation, trans-generation) and keywords related to review type (e.g., systematic, meta-analysis). We will not use language filters in grey literature searches. We will then screen the exported references for inclusion in our review.
We will perform a search update if more than 2 years passes since our original searches were performed before review completion.
Article screening and study eligibility criteria
We will use Rayyan QCRI [27] for abstract and full text screening. Two independent investigators will each screen all abstracts and full texts following the decision tree shown in Fig. 3. If any discrepancies occur, the two investigators will convene to discuss a logical resolution. If the investigators are unable to agree on a resolution, all authors will convene to decide on a logical resolution. We will record all discrepancies and justifications of the resolutions, and report a screening agreement score.
All search and screening results will be presented in a ROSES-type diagram. We will also provide a list of papers excluded at the full-text stage along with justification for exclusions. We will archive relevant bibliometric files and clearly document any alterations to the predefined protocol.
Language eligibility criteria All included full-text studies must be in English or in a language understood by the review team members (Japanese, Polish, Russian).
Definition of systematic reviews All systematic reviews (SRs) to be included in our map of systematic reviews must be within the ‘family’ of systematic reviews [23] and must be original or a re-analysis (i.e., providing a new contribution to our understanding of non-genetic inheritance). The SRs will be considered as being part of the SR family if the authors have at least conducted a systematic, rather than ad hoc, literature search and have screened the literature using selection criteria (note that we will conduct a critical appraisal of the included SRs, as mentioned under section "Study validity assessment"). The results of the included SRs may be reported in any form (i.e., a formal or informal meta-analysis, systematic map, rapid review, scoping review, or equivalent). We will exclude reviews not falling into our definition of the systematic review family as these reviews are not considered a rigorous method for synthesising the literature and cannot be critically assessed for quality with the established tools like CEESAT.
We will determine if a publication is eligible for inclusion in our map of systematic reviews by assessing if it meets our selection criteria specified using the PECO (Populations, Exposure, Comparators, Outcomes; [28] framework, as below).
Population We will include SRs on non-human species where there is clear separation of generations, as in most animals and plants. We will exclude SRs that focus exclusively on taxa that use asexual reproduction without clear separation of generations, such as budding, fragmentation or vegetative propagation. All included SRs must use experimental primary literature and must not solely use correlational studies due to the inability to directly assess the effects of environmental factors through manipulation while controlling for other factors in correlational studies. SRs exclusively on humans are excluded from our review as most human studies are purely correlational. Instead, we will include biomedical studies conducted on animals with goal of being applicable to humans, if they fulfil our inclusion criteria.
Exposure We will include SRs of F0 (ancestral generation) environmental exposures that fall within the following broad categories: (1) diet, (2) human-induced environmental pollutants/toxins, (3) natural variation in environmental composition (e.g., salt, nitrogen), (4) psychological stress (e.g., post-natal separation), (5) temperature, (6) ‘human health risk’ related environmental exposures (e.g., tobacco, alcohol), (7) differences in population demographics (e.g., population density, sex-ratio, impact of predators/grazers), (8) light and/or photoperiod, (9) other.
We will not include SRs that focus exclusively on human-related therapeutics/pharmaceutical drugs, such as medicines and physical procedures like surgeries and injections, as these are direct manipulations of the individual rather than a manipulation of the environment. However, we will include the effects of human-related medicines if such SRs are related to environmental toxicology and are investigating the effects of medicines as environmental pollutants. We will also not include any SRs that exclusively focus on the effects of polyandry (i.e., how many males the F0 female mates with) because differences in offspring phenotype are likely to be due to differences in paternity as females of some species can have mixed-paternity broods or bias sperm use from certain males [29].
The mode of trans-generational transmission considered in the SR must be non-genetic, with gametic or embryonic mode of transmission. We will record if the SR includes studies of factors that may induce DNA mutations. We will not include syntheses where the effects of F0 environment are conferred to offspring exclusively through parental care as this mechanism of the non-genetic inheritance occurs postnatally/post-hatching rather than through gametic or embryonic non-genetic transmission.
Comparators SRs need to compare F0 environmental exposure from within the categories presented above to either a control environment (e.g., standard laboratory or natural conditions deemed optimal for a given species) or two different ‘levels’ of the same type of environment (i.e., hot vs. cold temperature, high nutrient concentration vs low nutrient concentration).
Outcomes SRs must focus on the effects of F0 environment on phenotypic traits that are measured in F1 and/or subsequent (F2, F3…) generations. SRs will be categorised as including inter- and/or trans-generational effects (or mixture thereof), based on the focal taxa and the F0 sex exposed (see Fig. 1).
We will exclude SRs that entirely focus on F0 female fecundity or fertility (i.e., the number of offspring) as these are considered maternal traits rather than descendants’ traits. Descendants’ traits will be classified into the following broad categories: (1) physiological (e.g., immune function, insulin levels, hormone levels), (2) morphological (e.g., body size, adiposity, colouration), (3) reproductive (e.g., fecundity measures), (4) life-history (e.g., developmental rate, lifespan and aging), (5) behavioural (e.g., response to stimuli, anxiety, learning), (6) molecular (e.g., gene expression, DNA methylation), (7) health and disease (e.g., disease prevalence), and (8) other [30].