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Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

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

Gracy X. Rosario A , Serena J. D’Souza B , Dhananjay D. Manjramkar C , Vipul Parmar A , Chander P. Puri A and Geetanjali Sachdeva A D
+ Author Affiliations
- Author Affiliations

A Primate Biology Division, National Institute for Research in Reproductive Health, Indian Council of Medical Research, Jehangir Merwanji Street, Parel, Mumbai 400012, Maharashtra, India.

B Electron Microscopy Facility, National Institute for Research in Reproductive Health, Indian Council of Medical Research, Jehangir Merwanji Street, Parel, Mumbai 400012, Maharashtra, India.

C Animal House Facility, National Institute for Research in Reproductive Health, Indian Council of Medical Research, Jehangir Merwanji Street, Parel, Mumbai 400012, Maharashtra, India.

D Corresponding author. Email: ritugeet@vsnl.net

Reproduction, Fertility and Development 20(2) 281-294 https://doi.org/10.1071/RD07152
Submitted: 9 September 2007  Accepted: 29 October 2007   Published: 4 January 2008

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 α, 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 β-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.

Additional keywords: endometrium, oestrogen receptor, ultrastructure.


References

Albrecht, E. D. , Babischkin, J. S. , Lidor, Y. , Anderson, L. D. , Udoff, L. C. , and Pepe, G. J. (2003a). Effect of estrogen on angiogenesis in co-cultures of human endometrial cells and microvascular endothelial cells. Hum. Reprod. 18, 2039–2047.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Albrecht, E. D. , Aberdeen, G. W. , Niklaus, A. L. , Babischkin, J. S. , Suresch, D. L. , and Pepe, G. J. (2003b). Acute temporal regulation of vascular endothelial growth/permeability factor expression and endothelial morphology in the baboon endometrium by ovarian steroids. J. Clin. Endocrinol. Metab. 88, 2844–2852.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Arosh, J. A. , Banu, S. K. , Chapdelaine, P. , and Fortier, M. A. (2004). Temporal and tissue-specific expression of prostaglandin receptors EP2, EP3, EP4, FP, and cyclooxygenases 1 and 2 in uterus and fetal membranes during bovine pregnancy. Endocrinology 145, 407–417.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Bausero, P. , Cavaille, F. , Meduri, G. , Freitas, S. , and Perrot-Applanat, M. (1998). Paracrine action of vascular endothelial growth factor in the human endometrium: production and target sites, and hormonal regulation. Angiogenesis 2, 167–182.
PubMed |

Bentin-Ley, U. , and Lopata, A. (2000). In vitro models of human blastocyst implantation. Best Pract. Res. Clin. Obstet. Gynaecol. 14, 765–774.
Crossref | GoogleScholarGoogle Scholar |

Bentin-Ley, U. , Sjogren, A. , Nilsson, L. , Hamberger, L. , Larsen, J. F. , and Horn, T. (1999). Presence of uterine pinopodes at the embryo–endometrial interface during human implantation in vitro. Hum. Reprod. 14, 515–520.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Bhartiya, D. , Chowdhury, S. R. , and Bajpai, V. K. (1996). Stromal cell interaction and relevance to predecidual events and menstruation. Hum. Reprod. 11, 850–856.
PubMed |

Burton, G. J. , Hempstock, J. , and Jauniaux, E. (2001). Nutrition of the human fetus during the first trimester: a review. Placenta 22((Suppl. A)), S70–S76.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Carver, J. , Martin, K. , Spyropoulou, I. , Barlow, D. , Sargent, I. , and Mardon, H. (2003). An in-vitro model for stromal invasion during implantation of the human blastocyst. Hum. Reprod. 18, 283–290.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Chakraborty, I. , Das, S. K. , Wang, J. , and Dey, S. K. (1996). Developmental expression of the cyclo-oxygenase-1 and cyclo-oxygenase-2 genes in the peri-implantation mouse uterus and their differential regulation by the blastocyst and ovarian steroids. J. Mol. Endocrinol. 16, 107–122.
PubMed |

Cornillie, F. J. , Lauweryns, J. M. , and Brosens, I. A. (1985). Normal human endometrium. An ultrastructural survey. Gynecol. Obstet. Invest. 20, 113–129.
PubMed |

Coulam, C. B. , Roussev, R. G. , Thomason, E. J. , and Barnea, E. R. (1995). Pre-implantation factor (PIF) predicts subsequent pregnancy loss. Am. J. Reprod. Immunol. 34, 88–92.
PubMed |

Daftary, G. S. , and Taylor, H. S. (2001). Molecular markers of implantation: clinical implications. Curr. Opin. Obstet. Gynecol. 13, 269–274.
Crossref | GoogleScholarGoogle Scholar | PubMed |

David, G. X. , Herbert, J. , and Wright, G. D. S. (1973). The ultra structure of pineal glanglion in the ferret. J. Anat. 115, 52–79.


Deligdisch, L. , Yedwab, G. , Persitz, A. , and David, M. P. (1978). Ultra structural features in normal and hyperplastic postmenopausal endometrium. Acta Obstet. Gynecol. Scand. 57, 439–452.
PubMed |

Demir, R. , Kayisli, U. A. , Celik-Ozenci, C. , Korgun, E. T. , Demir-Weusten, A. Y. , and Arici, A. (2002). Structural differentiation of human uterine luminal and glandular epithelium during early pregnancy: an immunohistochemical and ultra structural study. Placenta 23, 672–684.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Dockery, P. , Pritchard, K. , Warren, M. A. , Li, T. C. , and Cooke, I. D. (1996). Changes in nuclear morphology in the human endometrial glandular epithelium in women with unexplained infertility. Hum. Reprod. 11, 2251–2256.
PubMed |

Dockery, P. , Ismail, R. M. , Li, T. C. , Warren, M. A. , and Cooke, I. D. (1997). The effect of a single dose of mifepristone (RU486) on the fine structure of the human endometrium during the early luteal phase. Hum. Reprod. 12, 1778–1784.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Edgar, D. H. , James, G. B. , and Mills, J. A. (1993). Steroid secretion by human early embryos in culture. Hum. Reprod. 8, 277–278.
PubMed |

Enders, A. C. (1989). Trophoblast differentiation during the transition from trophoblastic plate to lacunar stage of implantation in the rhesus monkey and human. Am. J. Anat. 186, 85–98.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Enders, A. C. , and Lopata, A. (1999). Implantation in the marmoset monkey: expansion of the early implantation site. Anat. Rec. 256, 279–299.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Enders, A. C. , Hendricx, A. G. , and Schlafke, S. (1983). Implantation in the rhesus monkey: initial penetration of endometrium. Am. J. Anat. 167, 275–298.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Ghosh, D. , and Sengupta, J. (1988). Patterns of estrogen and progesterone receptors in rhesus monkey endometrium during secretory phase of normal menstrual cycle and preimplantation stages of gestation. J. Steroid Biochem. 31, 223–229.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Ghosh, D. , and Sengupta, J. (1989). Estradiol and progesterone levels in the endometrium and the reproductive tract luminal washing during the pre-implantation stages of gestation in the rhesus monkey. Acta Endocrinol. 20, 649–654.


Ghosh, D. , and Sengupta, J. (2004). Endocrine and paracrine correlates of endometrial receptivity to blastocyst implantation in the human. Indian J. Physiol. Pharmacol. 48, 6–30.
PubMed |

Ghosh, D. , Roy, A. , Sengupta, J. , and Johannisson, E. (1993). Morphological characteristics of pre-implantation stage endometrium in the rhesus monkey. Hum. Reprod. 8, 1579–1587.
PubMed |

Ghosh, D. , De, P. , and Sengupta, J. (1994). Luteal phase ovarian oestrogen is not essential for implantation and maintenance of pregnancy from surrogate embryo transfer in the rhesus monkey. Hum. Reprod. 9, 629–637.
PubMed |

Gopalkrishnan, K. , Katkam, R. R. , Sachdeva, G. , Kholkute, S. D. , Padwal, V. , and Puri, C. P. (2003). Effects of an antiprogestin onapristone on the endometrium of bonnet monkeys: morphometric and ultrastructural studies. Biol. Reprod. 68, 1959–1967.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Greb, R. R. , Heikinheimo, O. , Williams, R. F. , Hogen, G. D. , and Goodman, A. L. (1997). Vascular endothelial growth factor in primate endometrium is regulated by oestrogen-receptor and progesterone-receptor ligands in vivo. Hum. Reprod. 12, 1280–1292.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Harkness, L. M. , and Baird, D. T. (1997). Morphological and molecular characteristics of living human fetuses between Carnegie stages 7 and 23: developmental stages in the post-implantation embryo. Hum. Reprod. Update 3, 3–23.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Helige, C. , Hagendorfer, G. , Smolle, J. , and Dohr, G. (2001). Uterine natural killer cells in a three-dimensional tissue culture model to study trophoblast invasion. Lab. Invest. 81, 1153–1162.
PubMed |

Hempstock, J. , Cindrova-Davies, T. , Jauniaux, E. , and Burton, G. J. (2004). Endometrial glands as a source of nutrients, growth factors and cytokines during the first trimester of human pregnancy: a morphological and immunohistochemical study. Reprod. Biol. Endocrinol. 2, 58.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Huang, J. C. , Liu, D. Y. , and Dawood, M. Y. (1998). The expression of vascular endothelial growth factor isoforms in cultured human endometrial stromal cells and its regulation by 17beta-oestradiol. Mol. Hum. Reprod. 4, 603–607.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Imakawa, K. , Chang, K. T. , and Christenson, R. K. (2004). Pre-implantation conceptus and maternal uterine communications: molecular events leading to successful implantation. J. Reprod. Dev. 50, 155–169.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Ing, N. H. , and Zhang, Y. (2004). Cell-specific expression of estrogen-responsive genes in the uteri of cyclic, early pregnant and ovariectomized ewes. Theriogenology 62, 403–414.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Kayisli, U. A. , Luk, J. , Guzeloglu-Kayisli, O. , Seval, Y. , Demir, R. , and Arici, A. (2004). Regulation of angiogenic activity of human endometrial endothelial cells in culture by ovarian steroids. J. Clin. Endocrinol. Metab. 89, 5794–5802.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Kim, J. J. , Wang, J. , Bambra, C. , Das, S. K. , Dey, S. K. , and Fazleabas, A. T. (1999). Expression of cyclooxygenase-1 and -2 in the baboon endometrium during the menstrual cycle and pregnancy. Endocrinology 140, 2672–2678.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Knoth, M. , and Larsen, J. F. (1972). Ultra structure of a human implantation site. Acta Obstet. Gynecol. Scand. 51, 385–393.
PubMed |

Kodaman, P. H. , and Taylor, H. S. (2004). Hormonal regulation of implantation. Obstet. Gynecol. Clin. North Am. 31, 745–766.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Lindenberg, S. , Hyttel, P. , Lenz, S. , and Holmes, P. V. (1986). Ultra structure of the early human implantation in vitro. Hum. Reprod. 1, 533–538.
PubMed |

Lindenberg, S. , Hyttel, P. , Sjogren, A. , and Greve, T. (1989). A comparative study of attachment of human, bovine and mouse blastocysts to uterine epithelial monolayer. Hum. Reprod. 4, 446–456.
PubMed |

Lindhard, A. , Bentin-Ley, U. , Ravn, V. , Islin, H. , Hviid, T. , Rex, S. , Bangsboll, S. , and Sorensen, S. (2002). Biochemical evaluation of endometrial function at the time of implantation. Fertil. Steril. 78, 221–233.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Manyonda, I. T. , and Choy, M. Y. (1999). Collagen phagocytosis by human extravillous trophoblast: potential role in trophoblastic invasion. J. Soc. Gynecol. Invest. 6, 158–166.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Marions, L. , and Danielsson, K. G. (1999). Expression of cyclo-oxygenase in human endometrium during the implantation period. Mol. Hum. Reprod. 5, 961–965.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Minas, V. , Loutradis, D. , and Makrigiannakis, A. (2005). Factors controlling blastocyst implantation. Reprod. Biomed. Online 10, 205–216.
PubMed |

Moudgal, N. R. , and Ravindranath, N. (1989). Requirement for estrogen in implantation and post implantation survival of blastocyst in the bonnet monkey. Prog. Clin. Biol. Res. 294, 277–288.
PubMed |

Murphy, C. R. (1995). The cytoskeleton of uterine epithelial cells: a new player in uterine receptivity and the plasma membrane transformation. Hum. Reprod. Update 1, 567–580.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Murphy, C. R. (2004). Uterine receptivity and the plasma membrane transformation. Cell Res. 14, 259–267.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Murray, M. K. (1992). The effect of estrogen and progesterone on structural changes in the uterine glandular epithelium of the ovariectomized sheep. Biol. Reprod. 47, 408–417.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Nikas, G. (1999). Cell-surface morphological events relevant to human implantation. Hum. Reprod. 14((Suppl. 2)), 37–44.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Nikas, G. , Drakakis, P. , Loutradis, D. , Mara-Skoufari, C. , Koumantakis, E. , Michalas, S. , and Psychoyos, A. (1995). Uterine pinopodes as markers of the ‘nidation window’ in cycling women receiving exogenous oestradiol and progesterone. Hum. Reprod. 10, 1208–1213.
PubMed |

Niklaus, A. L. , Murphy, C. R. , and Lopata, A. (2001). Characteristics of the uterine luminal surface epithelium at preovulatory and preimplantation stages in the marmoset monkey. Anat. Rec. 264, 82–92.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Padykula, H. A. , Fitzgerald, M. , Clark, J. H. , and Hardin, J. W. (1981). Nuclear bodies as structural indicators of estrogenic stimulation in uterine luminal epithelial cells. Anat. Rec. 201, 679–696.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Png, F. Y. , and Murphy, C. R. (2000). Closure of the uterine lumen and the plasma membrane transformation do not require blastocyst implantation. Eur. J. Morphol. 38, 122–127.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Puri, C. P. , Elger, W. A. G. , and Pongubala, J. M. R. (1987). Induction of menstruation by antiprogesterone ZK 98.299 in cycling bonnet monkeys. Contraception 35, 409–421.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Qualmann, B. , Kessels, M. M. , Thole, H. H. , and Sierralta, W. D. (2000). A hormone pulse induces transient changes in the subcellular distribution and leads to a lysosomal accumulation of the estradiol receptor alpha in target tissues. Eur. J. Cell Biol. 79, 383–393.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Ravindranath, N. , and Moudgal, N. R. (1987). Use of tamoxifen, an antioestrogen, in establishing a need for oestrogen in early pregnancy in the bonnet monkey (Macaca radiata). J. Reprod. Fertil. 81, 327–336.
PubMed |

Red-Horse, K. , Zhou, Y. , Genbacev, O. , Prakobphol, A. , Foulk, R. , McMaster, M. , and Fisher, S. J. (2004). Trophoblast differentiation during embryo implantation and formation of the maternal–fetal interface. J. Clin. Invest. 114, 744–754.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Rosario, G. , Sachdeva, G. , Okulicz, W. C. , Ace, C. A. , Katkam, R. R. , and Puri, C. P. (2003). Role of progesterone in structural and biochemical remodeling of endometrium. Front. Biosci. 8, S924–S935.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Rosario, G. X. , Modi, D. N. , Sachdeva, G. , Manjramkar, D. D. , and Puri, C. P. (2005). Morphological events in the primate endometrium in the presence of a preimplantation embryo, detected by the serum preimplantation factor bioassay. Hum. Reprod. 20, 61–71.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Roussev, R. G. , Barnea, E. R. , Thomason, E. J. , and Coulam, C. B. (1995). A novel bioassay for detection of preimplantation factor (PIF). Am. J. Reprod. Immunol. 33, 68–73.
PubMed |

Sharma, R. , Srivastava, S. , Bajpai, V. K. , and Balapure, A. K. (2002). Histological and ultra structural regulation in rabbit endometrial explants by estrogen in serum-free culture. In Vitro Cell. Dev. Biol. Anim. 38, 293–297.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Spornitz, U. M. (1992). The functional morphology of the human endometrium and decidua. Adv. Anat. Embryol. Cell Biol. 124, 20–60.


Sudha, S. , Kumari, U. , Rao, V. S. , and Rao, A. J. (1997). Identification of actin as an estradiol 17-beta-stimulated protein in the human placenta. Biochem. Mol. Biol. Int. 43, 955–966.
PubMed |

Sun, T. , Li, S. J. , Diao, H. L. , Teng, C. B. , Wang, H. B. , and Yang, Z. M. (2004). Cyclooxygenases and prostaglandin E synthases in the endometrium of the rhesus monkey during the menstrual cycle. Reproduction 127, 465–473.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Thie, M. , Fuchs, P. , Butz, S. , Sieckmann, F. , Hoschutzky, H. , Kemler, R. , and Denker, H. W. (1996). Adhesiveness of the apical surface of uterine epithelial cells: the role of junctional complex integrity. Eur. J. Cell Biol. 70, 221–232.
PubMed |

Thie, M. , Herter, P. , Pommerenke, H. , Durr, F. , Sieckmann, F. , Nebe, B. , Rychly, J. , and Denker, H. W. (1997). Adhesiveness of the free surface of a human endometrial monolayer for trophoblast as related to actin cytoskeleton. Mol. Hum. Reprod. 3, 275–283.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Usadi, R. S. , Murray, M. J. , Bagnell, R. C. , Fritz, M. A. , Kowalik, A. I. , Meyer, W. R. , and Lessey, B. A. (2003). Temporal and morphologic characteristics of pinopod expression across the secretory phase of the endometrial cycle in normally cycling women with proven fertility. Fertil. Steril. 79, 970–974.
Crossref | GoogleScholarGoogle Scholar | PubMed |