Theriogenology2011; 76(1); 61-73; doi: 10.1016/j.theriogenology.2011.01.018

Influences of treatment of early pregnant mares with the progestin altrenogest on embryonic development and gene expression in the endometrium and conceptus.

Willmann, C
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Budik, S
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Walter, I
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Aurich, C

Abstract: A positive influence of altrenogest treatment on a retarded development of the conceptus around the beginning of placentation in mares older than 8 years could be recently demonstrated. In the present study, effects of altrenogest treatment in early-pregnant mares on conceptus development and expression of endometrial and embryonic genes were investigated. Genes were chosen according to a possible involvement in embryo-maternal interaction and embryonic development in the equine species. Mares were treated with altrenogest (0.044 mg/kg bodyweight) or sunflower oil (placebo) from day 5 to 11 after ovulation. Embryos (altrenogest n = 13, placebo n = 12) and biopsies were collected on day 11. Pregnancy rate and embryonic size were not influenced by treatment (embryonic diameter: altrenogest 7.0 ± 2.5, placebo 6.5 ± 1.7 mm, n.s.). The percentage of luminal epithelial cells, superficial glandular epithelial cells and interstitial cells with nuclei staining positively for the progesterone receptor was significantly lower (P < 0.05) in samples collected from altrenogest-treated than from placebo-treated mares (e.g., luminal epithelium: altrenogest 1.9 ± 1.7%, placebo 23.0 ± 10.5%, P < 0.05). Staining for COX2 (cyclooxygenase-2) was not affected by treatment. In the endometrium a slight but significant increase in the number of PMN (polymorph nuclear neutrophils) was seen in response to treatment (altrenogest 0.8 ± 0.5 PMN/field, placebo 0.3 ± 0.3 PMN/field; P < 0.05). No differences in the relative gene expression of COX2, the receptors for progesterone, estrogens and growth hormone as well as for IGF (insulin-like growth factor) 1 and 2 were detected. The relative gene expression of aquaporin 3 in relation to β-actin differed significantly (P < 0.05) between embryos from altrenogest (3.2 ± 0.8) and placebo-treated mares (1.3 ± 0.2), but no other genes were affected. The study demonstrates down-regulation of progesterone receptors in the endometrium of early pregnant mares by treatment with the progestin altrenogest. This increased expression of aquaporin 3 in the conceptus was not related to changes in embryonic size or development.

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Publication Date: 2011-03-11 PubMed ID: 21396689DOI: 10.1016/j.theriogenology.2011.01.018Google Scholar: Lookup

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Summary

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This research examines the impacts of the progestin altrenogest on gene expression in early pregnant horses and the development of embryos. The study found that altrenogest treatment influences the activity of progesterone receptors and the expression of specific genes, although it does not significantly impact pregnancy rates or embryonic size.

Methodology

The research involved treating early pregnant mares with the progestin altrenogest at a dosage of 0.044 mg/kg of body weight from day 5 to 11 after ovulation. A group of mares were also treated with sunflower oil as a placebo for comparison.
On the 11th day, embryos and endometrial biopsies were collected. The embryos used in the study consisted of 13 from altrenogest-treated mares and 12 from placebo-treated mares.
A variety of genetic expressions and interactions in both embryos and the endometrium were examined, focusing on genes related to embryo-maternal interaction and embryonic development in horses.

Findings

The application of altrenogest did not have a significant impact on pregnancy rate or embryonic size.
However, the study did demonstrate a notable decrease in the percentage of luminal epithelial cells, superficial glandular epithelial cells, and interstitial cells that showed positive staining for the progesterone receptor in samples from the altrenogest-treated mares compared to the placebo group.
There was a slight but significant increase in the number of Polymorph Nuclear Neutrophils (PMNs) in the endometrium following treatment, while staining for cyclooxygenase-2 remained unaffected.
No noticeable variations in the relative gene expressions of cyclooxygenase-2, progesterone receptors, estrogen receptors, growth hormone receptors, as well as insulin-like growth factors 1 and 2, were detected.
The study found a significant difference between the relative gene expressions of aquaporin 3 in relation to β-actin in embryos from altrenogest and placebo-treated mares. However, this was not related to changes in embryonic size or development.

Significance

The research shows that treatment with altrenogest can downregulate progesterone receptors in the endometrium during early pregnancy in mares.
Moreover, altrenogest can influence the gene expression of aquaporin 3 within the embryo, even though this does not appear to affect embryonic development or size in any significant way.

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APA

Willmann C, Budik S, Walter I, Aurich C. (2011). Influences of treatment of early pregnant mares with the progestin altrenogest on embryonic development and gene expression in the endometrium and conceptus. Theriogenology, 76(1), 61-73. https://doi.org/10.1016/j.theriogenology.2011.01.018