Abstract
I reviewed a series of events in the mouse uterus before implantation on Day 4 of pregnancy (the sperm positive day is counted as Day 1). Major events are spacing of embryos along the uterine horns, shedding of the zona pellucida, and closure of the uterine lumen. How subtle they may be, there appear to exist interactions between intrauterine blastocysts and the uterus which is regulated by ovarian steroids. Spacing of embryos along the uterine horn is not random, but they are rather evenly distributed along the entire horn. The mechanism of even distribution of embryos needs clarification, although studies indicate that adrenergic nerve activity, prostaglandins, and other molecules appear to be involved. Shedding of the zona pellucida involves trypsin-like proteinase lysis of the zona. Through the opening created by zona lysis, blastocyst gets out of the zona by repeating expansion-collapse movements. Closure of rat uterine lumen is reported to be the result of absorption of uterine fluid through uterine glands. This needs to be confirmed in other species of rodents. Since these events influence blastocyst implantation, we need more detailed information on their regulatory mechanisms in order to improve the rate of healthy implantation of transferred embryo.
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References
Biggers JD, Leonov BV, Baskar JF, Fried J. Inhibition of hatching of mouse blastocysts in vitro by prostaglandin antagonists. Biol Reprod. 1978;19:519–33.
Bitton-Casimiri V, Brun JL, Psychoyos A. Comportement in vitro des blastocystes du 5e jour de la gestation chez la ratte; étude micro-cinematographique. CR Acad Sci Paris. 1970;270:2979–82.
Bowman P, McLaren A. The reaction of mouse lastocyst and its zona pellucida to enzymes in vitro. J Embryol Exp Morpholog. 1970;24:331–4.
Chen Q, Zhang Y, Peng H, Lei L, Kuang H, Ning L, et al. Transient β2-adrenoceptor activation confers pregnancy loss by disrupting embryo spacing at implantation. J Biol Chem. 2011;286:4349–56.
Chen Q, Zhang Y, Elad D, Jaffa AJ, Cao Y, Ye X, et al. Navigating the site for embryo implantation: biomechanical and molecular regulation of intrauterine embryo distribution. Mol Aspects Med. 2013;34:1024–42.
Evans CA, Kennedy TG. The importance of prostaglandin synthesis for the initiation of blastocyst implantation in the hamster. J Reprod Fertil. 1978;54:255–61.
Filant J, Spencer TE. Endometrial glands are essential for blastocyst implantation in the mouse uterus. Biol Reprod. 2013;88:1–9.
Finn CA. Increase in length of the uterus at the time of implantation in the mouse. J Reprod Fertil. 1968;17:69–74.
Hashima H. Studies on prenatal growth of the mouse with special reference to the site of implantation of the embryo. Tohoku J Agric Res. 1956;6:307–12.
Huet-Hudson Y, Dey SK. Requirement for progesterone priming and its long-term effects on implantation in the mouse. Proc Soc Exp Biol Med. 1990;193:259–63.
Kennedy TG. Evidence for a role for prostaglandins in the initiation of blastocyst implantation in the rat. Biol Reprod. 1977;16:286–91.
Kinoshita K, Satoh K, Ishihara O, Tsutsumi O, Nakayama M, Kashimura F, et al. Involvement of prostaglandins in implantation in the pregnant mice. Adv Prostaglandin Thromboxane Leukot Res. 1985;15:605–7.
Legrand C, Banuelos-Nevarez A, Rigolot C, Maltier JP. Comparative effects of 6-hydroxydopamine and α-adrenoceptor antagonists on intrauterine migration and spacing of blastocysts in the rat. J Reprod Fertil. 1987;81:51–8.
Li M, Yee D, Magnuson TR, Smithies O, Caron KM. Reduced maternal expression of adrenomedullin disrupts fertility, placentation, and fetal growth in mice. J Clin Invest. 2006;116:2653–62.
McCormack JT, Greenwald GS. Progesterone and oestradiol-17β concentrations in the peripheral plasma during pregnancy in the mouse. J Endocrinol. 1974;62:101–7.
McLaren A, Michie D. The spacing of implantations in the mouse uterus. In: Eckstein P, editor. Implantation of Ova. Memoirs of the Society for Endocrinology No.6 Cambridge University Press; 1959. p. 65–75.
Mintz B. Experimental study of the developing mammalian egg: removal of the zona pellucid. Science. 1962;138:594–5.
Mohamed OA, Jonnaert M, Labelle-Dumals C, Kuroda K, Clarke HJ, Dufort D. Uterine Wnt/β-catenin signaling is required for implantation. Proc Soc Nat Acad Sci U S A. 2005;102:8579–84.
Mossman HW. Comparative morphogenesis of the fetal membranes and accessory uterine structures. Contrib Embryol. 1937;158:133–25x.
Naftalin RJ, Thiagarajah JR, Pedley KC, Pocock VJ, Milligan SR. Progesterone stimulation of fluid absorption by the rat uterine gland. Reproduction. 2002;123:633–8.
Nichaman MZ. Inhibition of implantation by production of deciduomata in the rat. Am J Physiol. 1956;186:6–8.
Orsini MW, McLaren A. Loss of the zona pellucida in mice, and the effect of tubal ligation and ovariectomy. J Reprod Fertil. 1967;13:485–99.
O’Sullivan CM, Liu SY, Rancourt SL, Rancourt DE. Regulation of trypsin-related proteinase ISP2 by progesterone in endometrial gland epithelium during implantation in mice. Reproduction. 2001;122:253–44.
Paria BC, Ma W, Tan J, Raja S, Das SK, Dey SK, et al. Cellular and molecular responses of the uterus to embryo implantation can be elicited by locally applied growth factors. Proc Soc Nat Acad Sci. 2001;98:1047–52.
Paria BC, Nguyen H, Brown N, Reese J. Mechanisms involved in the loss of uterine receptivity at the site of post-partum uterine nodules. Abstract 2011 Annual meeting of Society for Gynecological Investigation.
Perona RM, Wassarman PM. Mouse blastocysts in vitro hatch by using a trypsin-like proteinase associated with cells of mural trophectoderm. Dev Biol. 1986;114:42–52.
Perry JS, Rowlands IW. Early pregnancy in the pig. J Reprod Fertil. 1962;4:175–88.
Potts DM, Wilson IB. The preimplantation conceptus of the mouse at 90 h at post coitum. J Anat. 1967;102:1–11.
Pusey J, Kelly WA, Bradshaw JMC, Porter DG. Myometrial activity and distribution of blastocysts in the uterus of the rat: interference by relaxin. Biol Reprod. 1980;23:394–7.
Psychoyos A. Retard de nidation de l’oef chez la ratte de aide de la chlorpromazine; action de l’oestrog ène. CR Acad Sci. 1959;248:3216–8.
Psychoyos A. Endocrine control of egg implantation. In: Greep RO, Astwood EB editors. Handbook of physiology. Section 7 endocrinology, vol 2 part 2. American Physiological Society; 1973. p. 187–215.
Quinn CE, Folkard C, Detmar J, Casper RF. Enhanced endocytotic and transcytotic activity in the rat endometrium prior to embryo implantation. J Mol Histol. 2008;39:409–15.
Racowsky C, Biggers JD. Are blastocyst prostaglandins produced endogenously? Biol Reprod. 1983;29:379–88.
Restall BJ, Bindon BM. The timing and variation of pre-implantation events in the mouse. J Reprod Fertil. 1971;24:423–6.
Ruan YC, Zhou W, Chan HC. Regulation of smooth muscle contraction by the epithelium: role of prostaglandins. Physiology. 2011;26:156–70.
Shelesnyak MC. Part II: Nidus formation. Acta Endocrinol. 1967;56:s47–75. doi:10.1530/acta.05650047.
Smith MS, Freeman ME, Neill JD. The control of progesterone secretion during the estrous cycle and early speudopregnancy in the rat: prolactin, gonadotropin and steroid levels associated with rescue of the corpus luteum of pseudopregnancy. Endocrinology. 1975;96:219–26.
Song H, Lim H, Paria BC, Matsumoto H, Swift LL, Morrow J, et al. Cytosolic phospholipase A2α deficiency is crucial for ‘on-time’ embryo implantation that directs subsequent development. Development. 2002;129:2879–89.
Wellstead JR, Bruce NW, Rahima A. Effects of indomethacin on spacing of conceptuses within the uterine horn and on fetal and placental growth in the rat. Anat Rec. 1989;225:101–5.
Wu JT. Precocious shedding of the zona pellucida in rats treated with progesterone. J Reprod Fertil. 1973;33:331–5.
Yang ZM, Das SK, Wang J, Sugimoto Y, Ichikawa A, Dey SK. Potential sites of prostaglandin actions in the periimplantation mouse uterus: differential expression and regulation of prostaglandin receptor genes. Biol Reprod. 1997;56:368–79.
Ye X, Hama K, Contos JJA, Anliker B, Inoue A, Skinner MK, et al. LPA3-mediated lysophosphatidic acid signaling in embryo implantation and spacing. Nature. 2005;435:104–8.
Ye X, Diao H, Chun J. 11-deoxy prostaglandin F2α, thromboxane A2 receptor agonist, partially alleviates embryo crowding in Lpar3 (−/−) females. Fertil Steril. 2012;97:757–63.
Yoshinaga K, Rice C, Krenn J, Pilot RL. Effects of nicotine on early pregnancy in the rat. Biol Reprod. 1979;20:294–303.
Yoshinaga K, Hawkins AR, Stocker JF. Estrogen secretion by the rat ovary in vivo during the estrous cycle and pregnancy. Endocrinology. 1969;85:103–12.
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Capsule This review paper summarizes a sequence of events that occurs in the mouse uterus on Day 4 of pregnancy.
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Yoshinaga, K. A sequence of events in the uterus prior to implantation in the mouse. J Assist Reprod Genet 30, 1017–1022 (2013). https://doi.org/10.1007/s10815-013-0093-z
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DOI: https://doi.org/10.1007/s10815-013-0093-z