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Published on: October 25, 2015
Developmental indices of nutritionally induced placental growth restriction in the adolescent sheep
Richard G Lea1, Lisa T Hannah, Dale A Redmer
1Ovine Pregnancy Group, Rowett Research Institute, Bucksburn, Aberdeen, Scotland. R.Lea@rri.sari.ac.uk
Insights
Overfeeding adolescent ewes restricted placental growth and reduced lamb birth weight. This study found reduced cell proliferation and increased apoptosis in restricted placentas, suggesting early gestation changes impact fetal development.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Animal Science
Background:
- Intrauterine growth restriction (IUGR) is often linked to impaired placental development.
- Adolescent ovine pregnancy models demonstrate that overfeeding can restrict placental growth and decrease lamb birth weight.
Purpose of the Study:
- To investigate the association between placental growth restriction and cellular processes like proliferation and apoptosis.
- To examine these cellular changes at day 81 of gestation, a critical period for placental growth.
Main Methods:
- Adolescent ewes with singleton pregnancies were fed high (H) or moderate (M) diets to influence placental size.
- Placental tissues were analyzed for cell proliferation using bromodeoxyuridine (Brd-U) incorporation and immunohistochemistry.
- Apoptosis-related gene expression (bax, mcl-1) and protein levels were assessed via in situ hybridization, Northern analyses, and Western analyses.
Main Results:
- Despite equivalent total placentome weights at term, the high-feed group (H) exhibited significantly lower Brd-U incorporation, indicating reduced cell proliferation.
- The H group showed significantly increased Bax protein levels, particularly in the fetal trophectoderm, suggesting elevated apoptosis.
- Expression of apoptosis regulatory genes (bax, mcl-1) was observed at the maternal-fetal interface.
Conclusions:
- Reduced placental size in this model may stem from diminished placental cell proliferation early in gestation.
- Increased placental apoptosis, indicated by elevated Bax protein, might also contribute to restricted placental growth.
- These findings highlight the critical role of early placental development in determining fetal growth outcomes.
Abstract:
Most intrauterine growth restriction cases are associated with reduced placental growth. Overfeeding adolescent ewes undergoing singleton pregnancies restricts placental growth and reduces lamb birth weight. We used this sheep model of adolescent pregnancy to investigate whether placental growth restriction is associated with altered placental cell proliferation and/or apoptosis at d 81 of pregnancy, equivalent to the apex in placental growth. Adolescent ewes with singleton pregnancies were offered a high or moderate level of a complete diet designed to induce restricted or normal placental size at term, respectively. Bromodeoxyuridine (Brd-U) was administered to H and M ewes 1 h before slaughter. Placental tissues were examined for a) Brd-U (immunohistochemistry) and b) apoptosis regulatory genes by in situ hybridization, Northern analyses (bax, mcl-1), immunohistochemistry, and Western analyses (bax). Quantification was carried out by image analysis. Total placentome weights were equivalent between groups. Brd-U predominantly localized to the trophectoderm and was significantly lower in the H group. Bax and mcl-1 mRNA were localized to the maternal-fetal interface. Bax protein was significantly increased in the H group and predominant in the uninuclear fetal trophectoderm. These observations indicate that reduced placental size at term may be due to reduced placental cell proliferation and possibly increased apoptosis occurring much earlier in gestation.
