Intrauterine degeneration of embryos in IUD-bearing mice

Abstract

, 1970). Fertilization, tubal transport and development of embryos appear to be unaffected in such animals, but the numbers of embryos that can be recovered by flushing the uterus at the time at which they can be expected to have entered the horns are smaller than those recoverable from controls (Marston & Kelly, 1969; and our unpublished data). Flushing therefore does not distinguish between intrauterine death or premature expulsion of embryos from the mouse uterus. In an attempt to discover the fate of embryos in IUD-bearing mice the following histological experiment was undertaken. Methods and resultsThe 6-8-week-old mice were of the LACA strain. Suture IUDs of braided silk (6/0 gauge) were inserted into the middle third of randomly-selected single horns at laparotomy. Control animals were sham-operated by passing a needle and silk through one horn. Following a rest period of 3 weeks females were mated during the final hour (09.00-10.00 h) of the 14-h dark period.Six IUD-bearing mice were killed at 72 h p.c., 6 at 96 h and a further 3 at 120 h. At autopsy, corpora lutea (CL) in both ovaries were counted under a dissecting microscope and the entire repro¬ ductive tract above the cervix was fixed in Bouin's fluid. Serial, longitudinal sections (7 pm) of the horns and oviducts were prepared and stained with haematoxylin and periodic acid-Schiff reagent. At least 300 sections per complete reproductive tract were examined for the presence and location of embryos.The results are summarized in Table 1. In the sham-operated controls examined at 72 and 96 h p.c., blastocysts were seen spaced along both uterine horns, and no polymorphonuclear leucocytes (PMNLs) were observed in the lumina of either the horns or the oviducts. In one animal killed at 96 hp.c. ovum attachment had occurred, and there was evidence of normal decidual cell development in the underlying stroma.In all IUD-bearing animals large masses of PMNLs were seen to surround the IUD and to extend from it towards both the ovarian and cervical extremities of the horn, frequently filling the lumen (PI. 1, Fig. 1). In two mice examined at 72 hp.c, 9 embryos were detected, all of them in the oviducts on the IUD side. In one of these animals 4 degenerated embryos were present (PL 1, Fig. 2), and in the other 5 apparently normal blastocysts were clustered in the isthmus. Small numbers of PMNLs were observed at the periphery of four of these embryos. In the other 4 animals examined at 72 hp.c. 18 embryos were detected in the horns, lying between the IUD and uterotubal junction, all being surrounded by PMNLs. These embryos lacked zonae pellucidae, probably due to their dissolution by the Bouin fixative. Mitotic figures were seen in several embryos, but 10 of 18 had hypertrophied and irregularly shaped cells, and appeared to be degenerating (PI. 1, Fig. 3). Fig. 4). Some embryos were considered to be degenerating, and in two horns PMNLs were observed between individual blastomeres (PI. 2, Fig. 5). Fewer PMNLs were found in the lumen, epithelium and stroma of the ...

In-vitro development of preimplantation embryos recovered from IUD-bearing mice

“…2 embryos/horn compared with 4-9/horn in control mice. This reduced yield has been reported before for mice (Doyle & Margolis, 1966;Marston & Kelly, 1969), but the rapid investment of embryos by the large mass of PMNLs seen in histological sections (Hurst et al, 1977a) Fig. 1.…”

“…From our present and previous results (Hurst et al, 1977a) it would appear that, in mice bearing an IUD, the developing embryo encounters either (i) a hostile non-cellular environment in the ovi¬ duct and/or uterus, or (ii) leukocytes in utero which attach to and subsequently penetrate embryos. These two mechanisms may operate, separately or jointly, in the mouse to suppress implantation in both uterine horns of animals bearing a unilateral IUD (Doyle & Margolis, 1966).…”

“…In addition, attempts were made to confirm the previous finding (Hurst et al, 1977a) that embryos collected from an IUD-containing uterine horn are actively invaded by leukocytes.…”

“…In mice fitted with a unilateral silk thread preimplantation embryos in the uterus were degenerated and surrounded by predominantly polymorphonuclear leukocytes (PMNLs) (Hurst, Jefferies, Eckstein & Wheeler, 1977a). Histological sections of the uteri revealed the presence of leukocytes within some of the embryos.…”

Varying effects of an IUD on decidualization in mice

“…At no dose combination did IUDs completely inhibit decidualization. (73) 10(67) 6(60) Experiment 3: effects of IUDs and hormone treatment in intact mated female mice Although IUDs of the type used here interrupt pregnancy in this strain of mice , it was possible that because they were inserted near the uterotubal junction they simply prevented passage of embryos or killed them in passing (Parr, 1969;Hurst, Jefferies, Eckstein & Wheeler, 1977), and did not directly inhibit implantation or decidualization. Experi¬ ments were therefore carried out to check that the IUDs interrupted pregnancy when they were placed elsewhere in the uterus and actually inhibited oil-induced decidualization, and also to see if the doses of hormones used in ovariectomized mice (see Exp.…”