# Proliferation and apoptosis studies of interplacental areas after aglepristone treatment for planned cesarean section in pregnant bitches

## TL;DR

This study examined the effects of aglepristone on cell proliferation and apoptosis in the canine uterus during planned C-sections, finding no significant differences compared to a control group.

## Contribution

The study is the first to investigate cell proliferation and apoptosis in the canine uterus during parturition using aglepristone.

## Key findings

- Aglepristone did not significantly affect serum progesterone levels or cell proliferation/apoptosis indices.
- Proliferation indices were <5% and apoptosis indices >45% in both treatment and control groups.
- No harmful effects of aglepristone were observed for planned C-sections in pregnant bitches.

## Abstract

Progesterone (P4) is the main hormone for pregnancy maintenance, occurring approximately 62–64 days after ovulation in bitches. Progesterone acts by binding to specific receptors. Aglepristone is a progesterone receptor (PR) antagonist with a higher affinity for PR binding. There are no published studies on cell proliferation and apoptosis in the canine uterus at the time of parturition. Therefore, this study aimed to determine the local effects of aglepristone on cell proliferation and apoptosis of interplacental uterine tissue during planned cesarean section (C-section) in bitches.

In this study, 13 client-owned French bulldogs were examined. Bitches were divided into treatment (n = 8) and control (n = 5) groups. Ovulation timing was predicted based on the serum P4 level on 62–64 days post-ovulation for parturition. Serum P4 levels were measured before (on 60-day post-ovulation) and on C-section day (on 61-day post-ovulation). Aglepristone (Alizine®), 15 mg/kg subcutaneously (SC), was administered on 60 days post-ovulation in the treatment group. A C-section was planned 20–24 h later, and interplacental uterine areas were collected from both groups during the C-section. Immunohistochemistry based on Ki-67 and TUNEL assay was used to evaluate cell proliferation and apoptosis in four different interplacental uterine tissue layers (epithelium, stroma, glandular epithelium, and myometrium). Data are reported as mean ± standard deviation. Kruskal–Wallis test was used for comparisons of more than two independent groups. P value of 0.05 was considered statistically significant.

One bitch in the treatment group was excluded due to emergency C-section 8 h after aglepristone administration. Serum P4 levels (ng/mL) at 20–24 h before and at C-section were 6.09 ± 2.72 and 4.32 ± 2.2 in the treatment group (n = 7) and 5.45 ± 1.28 and 3.67 ± 1.89 in the control group (n = 5), respectively. Proliferation (PI) and apoptotic (AI) indices were <5% and >45%, respectively, in both the treatment (n = 5) and control (n = 3) groups. PI and AI were detected at interplacental areas.

There were no significant differences in serum P4 levels or PI and AI indices between the groups. The PI <5% and AI was higher than 45% in both groups. Aglepristone did not have a direct effect on the serum P4 levels in both groups. These results correlated with the natural physiology of parturition preparation. Aglepristone 15 mg/kg SC injected 20–24 h before parturition had no effect on the P4 level, nor were any harmful effects observed for a planned C-section in pregnant bitches.