Secretory and Morphological Changes in the Baboon (Papio Anubis) Uterus and Placenta during Early Pregnancy1

Progesterone (P4) is unequivocally required to maintain a uterine environment conducive to pregnancy. This study investigated the effects of P4 treatment on expression of selected growth factors (fibroblast growth factor 7 [FGF7], FGF10, hepatocyte growth factor [HGF], and insulin-like growth factors [IGF1 and IGF2]), their receptors (MET, FGFR2(IIIB), and IGF1R), and IGF binding proteins (IGFBPs) in the ovine uterus. Ewes received daily injections of corn oil vehicle (CO) or 25 mg of P4 in vehicle from 36 h after mating (Day 0) to hysterectomy on Day 9 or Day 12. Another group received P4 to Day 8 and 75 mg of mifepristone (RU486, a P4 receptor antagonist) from Day 8 through Day 12. Endometrial FGF10 mRNA levels increased between Day 9 and Day 12 and in response to P4 on Day 9 in CO-treated ewes, which had larger blastocysts, and were substantially reduced in P4+RU486-treated ewes, which had no blastocysts on Day 12. Endometrial FGF7 or HGF mRNA levels were not affected by day or reduced by RU486 treatment, but MET mRNA levels were higher in P4-treated ewes on Day 9 and Day 12. Levels of IGF1, IGF2, and IGF1R mRNA in the endometria were not affected by early P4 treatment. Although stromal IGFBPs were unaffected by P4, levels of IGFBP1 and IGFBP3 mRNA in uterine luminal epithelia were increased substantially between Day 9 and Day 12 of pregnancy in CO-treated ewes and on Day 9 in early P4-treated ewes. Therefore, FGF10, MET, IGFBP1, and IGFBP3 are P4-regulated factors within the endometrium of the ovine uterus that have potential effects on endometrial function and peri-implantation blastocyst growth and development.

Section: Discussionmentioning

confidence: 99%

Progesterone Regulates FGF10, MET, IGFBP1, and IGFBP3 in the Endometrium of the Ovine Uterus1

Satterfield

Hayashi

Song

et al. 2008

“…It is possible that this differential expression of the two decidual proteins in the baboon is the result of the more programmed and delayed decidual response in the nonhuman primate in comparison to the human, as well as the potential requirement for a conceptus to complete the decidualization process [14,15]. Although the baboon decidual cells do not synthesize IGFBP-1 and prolactin at comparable time points, the cells that express IGFBP-1 in early pregnancy can be morphologically characterized as being decidual cells [16].…”

Section: Discussionmentioning

confidence: 99%

Comparative Studies on the In Vitro Decidualization Process in the Baboon (Papio anubis) and Human1

Kim

Jaffe

Fazleabas

1998

The process of decidualization involves the morphological and functional transformation of stromal fibroblasts to decidual cells. The objective of this study was to define appropriate in vitro culture conditions required for decidualization of baboon stromal cells. Parallel studies were also done with human endometrial stromal cells for comparative analysis. Human stromal cells produced prolactin and insulin-like growth factor-binding protein (IGFBP)-1 in response to hormones (estradiol-17beta [36 nM], medroxyprogesterone acetate [1 microM], and relaxin [100 ng/ml]), and production was enhanced in the presence of 0.1 mM dibutyryl cAMP (dbcAMP). By contrast, baboon cells did not produce any detectable levels of prolactin, even in the presence of hormones and dbcAMP. IGFBP-1 expression in baboon stromal cells was detectable by Day 6 of hormone and dbcAMP treatment and increased exponentially thereafter. In both human and baboon stromal cells, alpha smooth muscle actin (alphaSMA) expression, an early marker for decidualization in the baboon in vivo, was induced spontaneously under normal culture conditions. Furthermore, a decrease in alphaSMA expression was observed in cells producing high levels of IGFBP-1. Human cells produced significant levels of IGFBP-1 (p < or = 0.01) in response to short-term dbcAMP treatment (48 h) after 2 and 12 days of hormone treatment. However, baboon stromal cells required 17 days of hormonal treatment before cells became responsive to short-term dbcAMP treatment (p < or = 0.01). Finally, human endometrial stromal cells expressed the protein kinase A regulatory subunits RIalpha, RIbeta, RIIalpha, and RIIbeta whereas baboon stromal cells expressed RIalpha, RIIalpha, and RIIbeta. No difference in the mRNA expression of these isoforms was observed in decidualized or nondecidualized cells of either human or baboon endometrium. Our observations indicate that baboon stromal cells can be induced to decidualize in vitro and that this requires dbcAMP in addition to hormones. This is the first report demonstrating in vitro decidualization in a nonhuman primate.

“…A rare second-trimester hysterotomy specimen (from a therapeutic termination of pregnancy) was also studied (n ϭ 1). Paraffin-embedded sections of baboon uterus from pregnant, pseudopregnant, and cycling animals were obtained as previously described [24,25]. Additional tissues from pregnant baboons were kindly provided by Dr. Bambra (Institute for Primate Research, Nairobi, Kenya).…”

Section: Sample Collectionmentioning

confidence: 99%

Localization of Ubiquitin and Ubiquitin Cross-Reactive Protein in Human and Baboon Endometrium and Decidua during the Menstrual Cycle and Early Pregnancy1

Bebington

Bell

Doherty

et al. 1999

We have examined the distribution of ubiquitin and the related ubiquitin cross-reactive protein (UCRP) in paraffin-embedded sections of human and baboon endometrium and decidua by immunoperoxidase or immunofluorescence cytochemistry with antibodies raised against ubiquitin, UCRP, CD45, and insulin-like growth factor-binding protein-1. Anti-ubiquitin immunoreactivity was present in the nonpregnant endometrium, particularly in the glandular epithelial cells, and up-regulated in endometrial stromal cells as they decidualized at the beginning of pregnancy. Anti-UCRP immunoreactivity was absent from nonpregnant tissue but accumulated to high levels in decidual cells during pregnancy. Western blotting indicated that immunoreactivity was primarily due to the presence of ubiquitin and UCRP conjugated to other proteins, and that although levels of ubiquitin-protein conjugates do not change substantially during pregnancy, decidualization is accompanied by the appearance of conjugates of UCRP. Baboon uterine tissues demonstrated a similar distribution of the two proteins, which indicates that the baboon may be a useful model for study of the role of the ubiquitin system and UCRP in the establishment of pregnancy in humans.