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R L Gendron

Publications and source records attributed to R L Gendron.

24 records · Page 2Linked to original sources

Resorption of CBA/J x DBA/2 mouse conceptuses in CBA/J uteri correlates with failure of the feto-placental unit to suppress natural killer cell activity.

Lipid extraction was used to study the natural killer (NK) suppressive activity of individual feto-placental units. Normal pregnancies showed a lipophilic NK cell suppressive factor that was gestational day specific. Feto-placental units from CBA/J x DBA/2 pregnancies were deficient in the NK cell suppressive factor when compared to normal CBA/J x BALB/c pregnancies. The frequency of non-suppressive feto-placental units from CBA/J x DBA/2 pregnancies correlated with the frequency of feto-placental units infiltrated with NK cells and the frequency of spontaneous resorption. Our results implicate a deficiency of NK suppressive activity in the feto-placental unit as a contributing factor in spontaneous fetal resorption.

Animals↗

Lipopolysaccharide-induced fetal resorption in mice is associated with the intrauterine production of tumour necrosis factor-alpha.

Certain strains of mice display an increased frequency of fetal resorption, but little is known about the effector mechanisms involved. We have examined the events associated with lipopolysaccharide (LPS)-induced fetal resorption in mice. Administration of 25 micrograms LPS on Day 12 of gestation resulted in the appearance of tumour necrosis factor-alpha (TNF-alpha) in the amniotic fluid and fetal resorption. Levels of LPS-induced TNF-alpha were reduced by 90% after pretreatment with the TNF-alpha-suppressing drug pentoxifylline (PXF). Treatment of pregnant mice during early gestation with 0.1 micrograms LPS resulted in fetoplacental resorption which was maximal when the LPS was given on Day 8. Resorption induced by 0.1 micrograms LPS on Day 8 of gestation was significantly reduced by pretreatment with PXF. Infiltration of asialo-GM1-positive cells was observed in the decidual-ectoplacental cone area of embryonic units from LPS-treated mice. In addition, treatment with anti-AGM1 antiserum prevented the LPS-induced resorption. Our results suggest that TNF-alpha and asialo-GM1-positive cells are involved in LPS-induced fetal resorption.

Amniotic Fluid↗

Infiltrating decidual natural killer cells are associated with spontaneous abortion in mice.

Immunohistochemistry was used to study a murine model which spontaneously aborts at a frequency of 25 to 30%. Our results show that natural killer (NK) cells are not only the predominant infiltrating cells in aborting feto-placental units, but that they also appear in a similar proportion of feto-placental units before abortion is detectable. The frequency of feto-placental units with significantly elevated NK infiltrates corresponds to the subsequent abortion frequency, indicating a causal relationship. Immunization of the mother with BALB/C splenocytes prevents these NK infiltrates and decreases the abortion frequency to normal levels. These results suggest for the first time that maternal NK cells may have an instrumental role in the etiology of spontaneous abortion.

Animals↗

Morphometric analysis of the histology of spontaneous fetal resorption in a murine pregnancy.

Immunopathology of the spontaneous resorption phenomenon in the CBA x DBA/J murine model was explored using morphometric analysis. Accompanying the previously reported presence of natural killer (NK) cells in resorptive feto-placental units we find major changes in tissue morphology indicating that early infiltration of the feto-placental unit by maternal leukocytes plays a direct role with NK cells in fetal demise. Total number of cell nuclei per field and total nuclear area per field were significantly elevated in feto-placental units containing abnormally increased NK cell presence before detectable resorption as early as day 7 of gestation. This difference persisted throughout all stages of early gestation up to and including the final resorption event at day 10 to 12. Increases in cell density were also detected in areas of the embryonic unit not associated with NK infiltration. These results demonstrate that the spontaneous resorption phenomenon in this model involves: (i) Early (day 7-8) cellular infiltration of the decidual-ectoplacental cone junction associated with the presence in this area of NK cells. (ii) Late (day 8-9) cellular infiltration of the ectoplacental cone.

Animals↗