# Characterizing effects of sperm- and oocyte-derived epigenetic factors on early embryonic gene expression and offspring metabolic function

> **NIH NIH F31** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $31,015

## Abstract

PROJECT SUMMARY/ABSTRACT
Metabolic diseases such as obesity have become significant health risks affecting one-third of the population
worldwide and can have devastating complications. It is therefore imperative to understand the causes of
metabolic disease predisposition in order to develop preventative strategies. Extensive genetic studies have
failed to explain this ongoing epidemic. However, parents pass on not only genetic information, but also
epigenetic factors, which can be modified in response to environmental stimuli, and can then affect gene
expression. If information about parental environment can be recorded in the germline, it has the potential to be
transmitted to the zygote and impact offspring health. This concept remains controversial in mammals and
represents a large knowledge gap in the field of embryology. Previous work in the lab has demonstrated that
sperm from fathers fed a low protein diet carry tRNA fragments and microRNAs that can modify gene expression
in the embryo. Therefore, in Aim 1, sperm-derived RNAs will be purified and microinjected into
parthenogenetically-activated oocytes, or parthenotes, which lack any paternal genetic content.
Transcriptomic profiles of injected parthenotes will be acquired by single-embryo RNA-Seq to
characterize resulting alterations to the embryonic transcriptome. Maternal transmission of epigenetic
information has not been characterized to the same extent as the paternal side. Therefore, in Aim 2 a similar
dietary paradigm will be utilized to address the question of whether information about maternal diet can
be carried in oocytes and result in changes to the embryonic transcriptome. In vitro-fertilized embryos
from mothers fed low protein, high fat, or control diet will be sequenced by single-embryo RNA-Seq.
These embryos will be transferred to foster mothers to produce adult offspring, which will then be
assessed for glucose tolerance and insulin resistance. The use of in vitro fertilization in this paradigm will
ensure that any changes observed in the embryo originate from the oocyte and not from nutrient exchange during
gestation. Completion of this research will elucidate effects of paternal and maternal epigenetic factors carried
by gametes on the embryonic transcriptome.
This work will be completed at the University of Massachusetts Medical School under the sponsorship of Dr.
Oliver Rando. The fellowship training plan includes training in embryological techniques, such as microinjection
and immunofluorescent staining of lineage markers, as well as metabolic phenotyping of adult mice.
Opportunities to gain experience in science communication include participation in departmental seminars and
local and national conferences. Furthermore, career development workshops are provided by the university, in
addition to teaching and mentoring of first-year graduate students.

## Key facts

- **NIH application ID:** 10144829
- **Project number:** 5F31HD101232-02
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Marina Krykbaeva
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $31,015
- **Award type:** 5
- **Project period:** 2020-01-05 → 2023-01-04

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10144829

## Citation

> US National Institutes of Health, RePORTER application 10144829, Characterizing effects of sperm- and oocyte-derived epigenetic factors on early embryonic gene expression and offspring metabolic function (5F31HD101232-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10144829. Licensed CC0.

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