# NUTRITIONAL FACTORS IN MAMMALIAN DEVELOPMENT

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 1994 · $155,859

## Abstract

While there is agreement that zinc (Zn) deficiency interferes with
reproduction in experimental animals, and there is strong evidence that
suboptimal Zn status can be an etiological factor in human reproductive
disorders particularly when combined with other risk factors, there is
a paucity of information concerning the mechanisms by which Zn deficiency
acts.  This proposal examines potential mechanisms by which maternal and
embryonic/fetal Zn deficiency arise, and how this deficiency results in
abnormal development and growth and early fetal wastage (death during
preimplantation development).

We suggest that one mechanism by which this can occur is by Zn-deficiency
induced alterations in growth factor metabolism.  Thus, we will examine
the influence of Zn on the following factors:  epidermal growth factor
(EGF)/TGFalpha (transforming growth factor alpha), insulin, insulin-like
growth factor 1 (IGF I) and II (IGF II).

In addition to assessing the effects of Zn deficiency on growth factor
metabolism, we will test the hypothesis that an increased amount of
cellular oxidative damage is one consequence of fetal Zn deficiency which
contributes to fetal pathology.

We will use pre- and postimplantation embryo, and cell culture techniques
to confirm and extend results we obtain at the whole animal level.
Embryo culture systems will allow us to directly study the influence of
Zn status on the embryo.  In addition to studying the influence of media
Zn concentration on in vitro embryonic development, we will investigate
the role(s) of the Zn-binding protein metallothionein in embryonic
development.  This work will initially be done using anti-sense MT-mRNA
which we have recently shown affects preimplantation embryonic
development.  Integration of the information obtained at these individual
levels should allow us to adequately test the following hypothesis:  1)
Zn deficiency results in abnormal growth factor metabolism in pregnant
rats and mice and their conceptus.  2) Embryonic/fetal Zn deficiency is
associated with increases in the rate and extent of lipid, DNA, and
protein oxidation.  These increases contribute to the developmental
defects associated with Zn deficiency.  3) Embryonic/fetal Zn deficiency
can arise from a primary maternal Zn deficiency and/or from a disruption
of normal maternal Zn metabolism elicited secondary to a maternal acute
phase response.

## Key facts

- **NIH application ID:** 2194766
- **Project number:** 5R01HD001743-29
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **SAM.gov UEI:** TX2DAGQPENZ5
- **Principal Investigator:** Carl L. Keen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $155,859
- **Award type:** 5
- **Project period:** 1977-09-01 → 1997-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2194766

## Citation

> US National Institutes of Health, RePORTER application 2194766, NUTRITIONAL FACTORS IN MAMMALIAN DEVELOPMENT (5R01HD001743-29). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2194766. Licensed CC0.

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