The Relationship of Polymorphonuclear Leukocytes to Infertility in Uteri Containing Foreign Bodies

Parr, Earl L.; Schaedler, Russell W.; Hirsch, James G.

doi:10.1084/jem.126.3.523

Cited by 89 publications

(38 citation statements)

References 17 publications

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“…In the majority of species studies so far an IUD induces a cellular (PMNL or macrophage) invasion of the uterine lumen, and this feature appears to be an important aspect of intrauterine contraception (see Greenwald, 1965;Parr, Schaedler & Hirsch, 1967;El Sahwi & Moyer, 1971;Cuadros & Hirsch, 1972;Bo, Krueger & Bartley, 1974;Myatt, Bray, Gordon & Morley, 1975). The present observations strongly support the view that in the mouse a silk IUD exerts its antifertility action principally by leucocyte-mediated degeneration of uterine embryos, and partly by retention of embryos in the oviduct.…”

Section: Discussionsupporting

confidence: 78%

Intrauterine degeneration of embryos in IUD-bearing mice

Hurst¹,

Jefferies²,

Eckstein³

et al. 1977

Reproduction

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, 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be expected to have entered the horns are smaller than those recoverable from controls (Marston & Kelly, 1969; and our unpublished data).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 ...

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Section: Discussionsupporting

confidence: 78%

Intrauterine degeneration of embryos in IUD-bearing mice

Hurst¹,

Jefferies²,

Eckstein³

et al. 1977

Reproduction

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“…These effects on the endometrium may reduce the subsequent viability of embryos managing to survive the toxic effects of the copper IUD and in this way explain the increased effective¬ ness of the copper IUD over the conventional inert IUD as reported by Zipper, Tatum, Pastene, Medel & Rivera (1969). On the other hand, Parr, Schaedler & Hirsch (1967) …”

Section: Discussionmentioning

confidence: 96%

The Contraceptive Action of the Copper Iud in the Rat

Webb¹

1973

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Summary. Experiments are described that were designed to show the time and site of the contraceptive action of an intrauterine copper device in the rat. The IUD had no effect on fertilization. Progressively fewer embryos survived, the later the device was removed during the afternoon and evening of the 4th day of pregnancy. The presence of the IUD for the first few hours only of embryonic life completely suppressed implantation, causing death of the embryos. Exposure of the pseudopregnant uterus to copper for the same period was unable to affect the decidual response to traumatization. It was concluded that the contraceptive action of the copper is due to the fact that its presence results in an embryotoxic environment which causes the death of the embryos before any noticeable effect on the endometrium. As the embryos are not killed immediately they enter the uterine lumen, it is likely that death occurs at a time in the development of the embryo when it becomes sensitive to the toxins. Such a time could be the period of transition from the morula stage to the blastocyst.

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“…Lysosomal enzymes such as /?-glucuronidase (Parr, 1969) and lysozyme (Parr, Schaedler & Hirsch, 1967) have been reported to be released into the uterine lumen of the rat during chronic leucocyte infiltration under the influence of intrauterine foreign bodies, but the concentration of leucocytes in the uterine lumen during a normal pregnancy does not appear to increase and would probably be detri¬ mental to the pregnancy if it did. There is a possibility, however, that prefer¬ ential release of certain lysosomal enzymes may occur from endometrial cells under the action of progesterone which is reported to decrease the stability of the lysosomal membrane (Weissman, 1969).…”

Section: Tions Discussionmentioning

confidence: 99%