Endometrial modifications during early pregnancy in bonnet monkeys (Macaca radiata)

Abstract

The present study was undertaken to investigate endometrial modifications that occur before embryo invasion in bonnet monkeys (Macaca radiata). These changes were analysed in luminal epithelium, glandular epithelium and stroma of endometrial functionalis on Day 6 post ovulation from pregnant and non-pregnant animals (n = 4 each) by transmission electron microscopy. Distinct features (i.e. loss of columnar shape by epithelial cells, changes in mitochondrial size and diffused apicolateral gap junctions) were observed in the luminal and glandular epithelium in pregnant animals. Stromal compaction was also observed in pregnant animals. Further, immunogold localisation studies demonstrated significantly higher expression (P < 0.05) of oestrogen receptor alpha, an oestrogen-regulated gene, in the glandular epithelium and stroma of the endometrium in pregnant animals compared with non-pregnant animals. Expression of two other genes known to be regulated by oestradiol, namely beta-actin and cyclo-oxygenase-1, were also significantly higher (P < 0.05) in the endometria of pregnant animals. These studies demonstrate marked changes in the endometrium before embryo invasion in bonnet monkeys. These studies also indicate altered oestrogenic activity in the uterine milieu before embryo invasion.

Expression of Endometrial Protein Kinase A During Early Pregnancy in Bonnet Monkeys (Macaca radiata)1

“…Therefore, this alternate pathway may become functional during the early stages of decidualization in which stromal cells undergo a wave of proliferation. In accordance, we have observed an increase in stromal cell proliferation during early pregnancy in bonnet monkeys [24]. The present study revealed that pregnant bonnet monkeys had higher expression of PTGS2 in endometrial stroma.…”

“…Our previous investigations demonstrated altered expression of estrogen-responsive genes such as estrogen receptor alpha in bonnet monkey endometrium during early pregnancy [24]. This is in contrast to sheep, in which loss of estrogen receptor alpha was observed during the periimplantation period [17].…”

“…However, these species differ from humans with respect to the day of initiation of implantation. In bonnet monkeys (Macaca radiata), implantation is initiated on Day 7 after ovulation, a time point approximating the day of implantation in humans [24]. Considering this, we developed a bonnet monkey model to investigate the molecular and structural changes induced by a preimplantation-stage embryo on Day 6 after ovulation in endometrium just before attachment.…”

“…Our previous investigations have hinted that angiogenic, immunomodulatory, and proliferative pathways become operative even before intimate physical contact is established between the blastocyst and endometrium. Valuable information has been gained from these studies [24][25][26][27] on the expression pattern in gestational endometrium of those molecules (e.g., prolactin, alpha smooth muscle actin, transforming growth factor beta and its receptor, tumor necrosis factor and its receptor, etc.) previously investigated only for their hormonal regulation and/or possible role in endometrial receptivity.…”

Estrogenic control of mitochondrial function and biogenesis

“…mtDNA copy number is a measure of mitochondrial biogenesis. Increased numbers of mitochondria and increased mitochondrial size were observed in the glandular epithelium and stromal endometrium of pregnant bonnet monkeys, an effect attributed to increased E 2 [Rosario et al, 2008]. We reported that E 2 significantly increased mtDNA copy number after 24, 48, and 72 h. in MCF-7 cells [Mattingly et al, 2008].…”