Table 1.

Paternal inheritance of metabolic traits. This table recapitulates findings from all available studies reporting paternal inheritance of metabolic traits and their association with tRNA fragments present in sperm. HFD, high fat diet; IVF, in vitro fertilization; NC, normal chow, tRHs, tRNA halves.

	F0 (Diet or Genotype)		Offspring Phenotype
Rodent Model and Breeding Method	F0 ♂	F0 ♀	F1	F2	Mechanism Unveiled	Reference Number
Rat/Natural mating	HFD	NC	♀ β -cell dysfunction (glucose intolerance, ↓ insulin secretion)	-	642 differentially expressed genes in F1 islets. Hypomethylation of the Il13ra2 gene	[201]
Mouse/Natural mating	24 h premating fasting	NC	♂and♀ ↓ non fasting glycemia	-	-	[202]
Mouse/Natural mating	Multiple low dose streptozotocin	NC	♂ Insulitis ↓ insulin secretion	-	-	[203]
Mouse/Natural mating	HFD	NC	♂and♀ Glucose intolerance Insulin resistance	-	Altered expression of genes involved in glucose homeostasis and insulin secretion in F1 islets. Altered cytosine DNA methylation in F1 islets and F0 sperm.	[204]
Mouse/IVF (using all gamete combinations)	6 weeks on HFD or NC	6 weeks on NC or HFD	♂and♀ ↑ susceptivility to develop obesity and diabetes in progeny from HFD-fed F0 respect to progeny from NC-fed F0	-	-	[205]
Mouse/ IVF or zygote microinjection of total RNA or tRHs isolated from sperm from HFD-fed males	HFD	NC	♂and♀ Glucose intolerance Insulin resistance (only after IVF)	-	↑ m5C and m5G in F0 sperm tRNAs. ↑ 5′-tRH in F0 sperm. ↓ expression of genes involved in metabolic regulation pathways in 8 cell F1 embryos.	[30,55]
Mouse/Natural mating	Congenic model of obesity and pre-diabetes Avy/a mouse) NC	NC (a/a)	♂and♀ ↑ obesity, glucose intolerance and insulin resistance in HFD-fed offspring of Avy/a mice respect to control mice	♂and♀ ↑ obesity, glucose intolerance and insulin resistance in the progeny of Avy/a grandfathers (even if F1 males were fed NC)	miRNA and tRH changes in F1 sperm from Avy/a fathers respect to F1 from control fathers: ↑ 5′-tRHGly(CCC) and ↓ 5′-tRHGlu(CTC).5′-tRHsGlu(CTC) binds to Argonaute and may act as miRNA regulating gene expression.	[208]
Rat/ Natural mating	HFD for 12 weeks	NC	♀↓ β-cell mass Glucose intolerance	♀ ↓ insulin secretion Glucose intolerance	DNA methylation changes in sperm from F0 and F1. Differential expression of miRNAs and 41 tRNA fragments.	[209]
Mouse/ Natural mating in F0 (the F2 generation was obtained by microinjection of total RNA or 5-tRHs from F1 sperm into normal zygotes)	NC	HFD for 9 weeks	♂and ♀ ↑ weight gain ↑ blood glucose ↑ insulin secretion ↑ obesogenic eating phenotype ↑addictive-like behaviour		Identification of 13 differentially expressed 5′-tRHs in sperm from F1 derived from HFD-mothers.	[210]