# Low-Dosage Rumen Unprotected Creatine Precursor During the Transition Period in Single-Bearing Ewes Impacts Dynamic Changes in Muscle and Adipose Mass, Uterine Involution, and Fetal Programming Outcomes

**Authors:** Larissa Fernandes Baia Cesar, Alfredo José Herrera Conde, Camila Muniz Cavalcanti, Bruna Vitória de Freitas Alves, Marta da Costa Sousa, Jhennyfe Nobre de Sena, Yohana Huicho Miguel, Fernando Felipe da Silva Pereira, Louhanna Pinheiro Rodrigues Teixeira, Juliana Paula Martins Alves, César Carneiro Linhares Fernandes, Aníbal Coutinho do Rêgo, Dárcio Ítalo Alves Teixeira, Davide Rondina

PMC · DOI: 10.3390/vetsci13010097 · Veterinary Sciences · 2026-01-19

## TL;DR

Adding a low dose of GAA to the diet of pregnant ewes affects muscle and fat changes, uterine recovery, and fetal development, but also reduces birth weight.

## Contribution

This study is the first to show GAA's effects on uterine involution and fetal programming in single-bearing ewes.

## Key findings

- GAA improved postpartum uterine involution and mammary gland development.
- GAA reduced offspring birth weight and altered maternal-fetal communication.
- GAA increased feed intake and antioxidant levels in ewes after delivery.

## Abstract

Guanidinoacetic acid (GAA) is a promising nutritional supplement with recognized productive results in cattle and sheep. Thanks to its ruminal escape capacity, it represents a viable option among metabolic stimulators due to its lower cost and ease of inclusion in the diet. However, few studies have evaluated its reproductive impacts, particularly during challenging stages such as late gestation and early lactation, which encompass multiple fundamental events for both dam and offspring. Thus, in the present study, supplementation with a low dose of GAA throughout the transition period in single-bearing ewes allowed us to observe distinct effects of the product on the fetal vascular system and on the birth weight of the offspring, as well as improving the dynamics of the uterine involution process postpartum. GAA mitigated tissue depletion after parturition in females and aided in the development of the mammary gland as well as the growth of the lamb.

Little is known about the reproductive impacts of the GAA, creatine precursor, in ruminants. This study aimed to evaluate the effects of GAA supply during the transition period in ewes with single pregnancies on their uterine involution. Sixteen ewes with single pregnancy were allocated to two groups: one receiving a basal diet (WGAA, n = 8) and another receiving a basal diet supplemented daily with 0.6 g/kg DM diet of GAA (RUGAA, n = 8) from 100 days of gestation to 35 days postpartum (PP). The RUGAA group showed increased feed intake after delivery and modified diet selectivity. Also, at parturition, a smaller cotyledonary surface area and lower offspring weight at birth were observed. During PP, RUGAA exhibit a slight reduction in the loin depth and backfat thickness, and higher peripheral glutathione peroxidase level. Also in PP, RUGAA expressed a greater rate of uterine lumen shrinkage, more efficient mammary parenchyma growth and a higher relative lambs growth rate. We concluded that supplementation with 0.6 g of GAA in ewes with single pregnancies improved postpartum uterine involution, but also altered the mother-fetus communication system, affecting the birth weight of the offspring. Therefore, we believe further studies are necessary to efficiently align creatine demand with the distinct physiological events that occur during gestation and the postpartum period.

## Linked entities

- **Chemicals:** Guanidinoacetic acid (PubChem CID 763), GAA (PubChem CID 10465927)

## Full-text entities

- **Chemicals:** RUGAA (-), GAA (MESH:C043055), Creatine (MESH:D003401)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12846475/full.md

## References

78 references — full list in the complete paper: https://tomesphere.com/paper/PMC12846475/full.md

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Source: https://tomesphere.com/paper/PMC12846475