Run for your sons Quiz 2 paper

paternal intergenerational transmission of epigenetic regulation. Transmission via microRNA carried by the paternal gamete, sperm.

what was the basic finding of the research discussed in the article?

(Environmental factor, inherited phenotype)

Exercise in father → changed sperm miRNA → reduced Ncor1 in embryo → fitness phenotype in offspring

The basic finding of the research of his was in mice, paternal exposure to environmental stimuli of exercise-training (treadmill 8 weeks) significantly influenced the expression of inherited phenotypes of increased fitness ability and altered metabolism in their progeny, via alteration of miRNA 148 in sperm and subsequent repression of NCor1.

Paternal diet and exercise influence metabolic state of progeny - Sperm RNA’s can transmit environmentally regulated, non-genetically inherited phenotypes.

what findings of Yin’s support the above connections between paternal behavior and their offspring phenotype

Yin compared the progeny of mice that were excericed on a treadmill for 8 weeks, to the progeny of sedentary mice.

The progeny of exercised mice showed better endurance on treadmill, increased oxygen consumption, increased oxidative muscle fiber subtypes and mitochondria in the gastrocnemius.

They also found that small rna from sperm of exercised males was enough to transfer the phenotype when injected into naive zygotes, which shows the information was carried by the sperm RNA

Even further, they found similar small rna changes in both exercised mice and humans, strengthening confidence in the exercise linked sperm RNA signal.

what is the experiment that was done to confirm the sperm content of microRNA is specifically what causes the offspring phenotype?

The key confirmation experiment was zygotic microinjection:

They isolated the sperm small rna from exercised males and injected it into normal fertilized eggs, and that was sufficient to reproduce the offspring fitness phenotype.

That experiment shows that the effect was carried by the RNA, not by the sperm dna sequence or by the father’s body directly.

How did they identify miRNA 148 as the one that is responsible for this phenomenon?

Small RNA sequencing was done on the sperm of exercise trained mice and humans, both showed miRNA 148 was altered. Its alteration stood out in both mice and humans, and also overlapped with changes seen in the pGC1a over-expression model. When they injected miRNA into zygotes, it was sufficient in reproducing the improved fitness phenotypes in the F1 progeny, identifying miR-148 as a key modulator.

Give the brief description of microRNA function mentioned in the paper, and how it is connected to the expression the Ncor1 in the zygote.

MicroRNA regulates gene expression by binding to target mRNAs, preventing their translation. In the study, miRNA plays a role in modulating Ncor1 expression in the zygote, which is important for subsequent development and phenotype. The study showed that altered sperm w/increased miR-148 led to decreased embryonic NCoR1 expression, and this early impression led to improved fitness phenotype in F1.

What are the different models they author proposed for how paternal exercise alters microRNA in sperm.

• Exercise could change systemic metabolism, which then alters miRNA production during spermatogenesis

• Exercise could act on the epididymis, changing extracellular vesicles that deliver miRNAs to sperm during maturation

• Exercise could influence the immune system or microbiome, which then signal to the germline or epididymis and indirectly change sperm small RNAs.