Related Experiment Video
Updated: Mar 27, 2026

Mouse In Vivo Placental Targeted CRISPR Manipulation
Published on: April 14, 2023
Gestational protein restriction alters cell proliferation in rat placenta
Hércules Jonas Rebelato1, Marcelo Augusto Marreto Esquisatto1, Eloá Fernanda de Sousa Righi1
1Biomedical Sciences Graduate Program, Centro Universitário Hermínio Ometto, UNIARARAS, Av Maximiliano Baruto, 500, 13607-339, Araras, SP, Brazil.
Insights
Gestational protein restriction (GPR) impairs placental development by inhibiting cell proliferation and causing early aging. This leads to reduced placental weight and fetal growth restriction in offspring.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Nutritional Science
Background:
- Gestational protein restriction (GPR) is known to affect placental structure.
- Investigating the impact of GPR on placental cell proliferation and development is crucial.
Purpose of the Study:
- To examine the spatial and temporal immunolocalization of the proliferating cell antigen Ki67.
- To understand the effects of GPR on placental development and cell proliferation.
Main Methods:
- Wistar rats were fed either a normal (17% casein) or low-protein (6% casein) diet.
- Placentas and fetuses were collected at 15, 17, 19, and 21 days post-conception.
- Morphological, morphometric, ultrastructural, and Ki67 immunolocalization analyses were performed.
Main Results:
- Low-protein diet reduced trophoblast giant cells, glycogen cells, and placental weight at 17 days.
- GPR inhibited cell proliferation in the junctional zone (JZ) and increased labyrinth zone (LZ) thickness.
- Ultrastructural changes suggested enhanced placental aging in GPR animals.
- Offspring from protein-restricted dams were significantly lighter.
Conclusions:
- GPR significantly alters placental morphology and inhibits cell proliferation, particularly in the JZ.
- These placental changes are associated with enhanced aging and fetal growth restriction.
- GPR negatively impacts fetal development and offspring weight.
Abstract:
We recently showed that gestational protein restriction (GPR) alters the structure of the rat placenta on day 19 of gestation (dG). The aim of the study was to investigate the spatial and temporal immunolocalization of proliferating cell antigen Ki67 in normal and GPR placental development. Pregnant Wistar rats were divided into two groups: normal (NP, 17 % casein) or low-protein diet (LP, 6 % casein). Placentas and fetus were collected and weighed at 15, 17, 19 and 21 dG. Morphological, morphometric and ultrastructural analyses were performed. Immunoperoxidase was used to identify nuclear antigen Ki67 in placental sections. We observed a significant reduction in the number of trophoblast giant cells and glycogen cells in the LP group. Placental weight was significantly reduced only at 17 dG in the LP group, in parallel to a decrease in glycogen cells. From 15 to 21 dG, the thickness of the junctional zone (JZ) decreased in NP and LP animals, while that of the labyrinth zone (LZ) increased in parallel to a reduction in the number of proliferating cells in this LZ zone. GPR significantly inhibits cell proliferation in the JZ, especially at 15 and 17 dG. The ultrastructural appearance of the cytoplasm of giant and cytotrophoblastic cells indicates degeneration from 15 to 21 dG and this effect is enhanced in LP animals suggesting early aging. Offspring of NP dams were significantly heavier than offspring of LP dams at 21 dG. GPR causes modifications in specific regions of the placenta, cell proliferation inhibition and fetal growth restriction.

