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Impaired leukocyte influx in cervix of postterm women not responding to prostaglandin priming.

Sahlin L, Stjernholm-Vladic Y, Roos N, Masironi B, Ekman-Ordeberg G - Reprod. Biol. Endocrinol. (2008)

Bottom Line: Post term women could be divided into at least two subgroups, one where parturition is possible to induce by prostaglandins and one where it is not.Our aim was to study parameters in cervical biopsies in women with spontaneous delivery at term (controls) and compare to those that are successfully induced post term (responders), and those that are not induced (non-responders), by local prostaglandin treatment.The impaired leukocyte influx, as reflected by the reduced number of CD45 positive cells as well as decreased immunostaining of IL-8, PAF-R and MMP-9 in the non-responders, could be one explanation of the failed ripening of the cervix in post term women.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division for Reproductive Endocrinology, Q2:08, Karolinska University Hospital-Solna, Karolinska Institutet, Stockholm, Sweden. Lena.Sahlin@ki.se

ABSTRACT

Background: Prolonged pregnancies are associated with increased rate of maternal and fetal complications. Post term women could be divided into at least two subgroups, one where parturition is possible to induce by prostaglandins and one where it is not. Our aim was to study parameters in cervical biopsies in women with spontaneous delivery at term (controls) and compare to those that are successfully induced post term (responders), and those that are not induced (non-responders), by local prostaglandin treatment.

Methods: Stromal parameters examined in this study were the accumulation of leukocytes (CD45, CD68), mRNAs and/or proteins for the extracellular matrix degrading enzymes (matrix metalloproteinase (MMP)-2, MMP-8 and MMP-9), their inhibitors (tissue inhibitor of MMP (TIMP)-1 and TIMP-2), interleukin-8 (IL-8), the platelet activating factor-receptor (PAF-R), syndecan-1 and estrogen binding receptors (estrogen receptor (ER)alpha, ERbeta and G-coupled protein receptor (GPR) 30) as well as the proliferation marker Ki-67.

Results: The influx of leukocytes as assessed by CD45 was strongest in the responders, thereafter in the controls and significantly lower in the non-responders. IL-8, PAF-R and MMP-9, all predominantly expressed in leukocytes, showed significantly reduced immunostaining in the group of non-responders, while ERalpha and GPR30 were more abundant in the non-responders, as compared to the controls.

Conclusion: The impaired leukocyte influx, as reflected by the reduced number of CD45 positive cells as well as decreased immunostaining of IL-8, PAF-R and MMP-9 in the non-responders, could be one explanation of the failed ripening of the cervix in post term women. If the decreased leukocyte influx is a primary explanation to absent ripening or secondary, as a result of other factors, is yet to be established.

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Related in: MedlinePlus

Immunostaining results of CD45, CD68 and PAF-R. CD45 (top), CD68 (middle) and PAF-R (bottom) immunostaining results in stroma, as assessed by image analysis (top) and manual scoring (middle, bottom) in cervical samples from controls (C) (n = 18), responders (R) (n = 13) and non-responders (NR) (n = 9). The "box-and-whisker plot" represents the median value with 50% of all data falling within the box. The whiskers extend to the 5th and 95th percentiles. Boxes with different letter designations are significantly different, p < 0.05.
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Figure 1: Immunostaining results of CD45, CD68 and PAF-R. CD45 (top), CD68 (middle) and PAF-R (bottom) immunostaining results in stroma, as assessed by image analysis (top) and manual scoring (middle, bottom) in cervical samples from controls (C) (n = 18), responders (R) (n = 13) and non-responders (NR) (n = 9). The "box-and-whisker plot" represents the median value with 50% of all data falling within the box. The whiskers extend to the 5th and 95th percentiles. Boxes with different letter designations are significantly different, p < 0.05.

Mentions: Immunostaining of CD45 showed that there are less leukocytes in the NR group than in the responders (Figure 1, upper panel; Figure 2A–C), indicating that prostaglandin treatment, when successful, induces leukocyte influx. CD68 immunostaining (Figure 2M) showed no significant difference between groups (Figure 1, middle panel).


Impaired leukocyte influx in cervix of postterm women not responding to prostaglandin priming.

Sahlin L, Stjernholm-Vladic Y, Roos N, Masironi B, Ekman-Ordeberg G - Reprod. Biol. Endocrinol. (2008)

Immunostaining results of CD45, CD68 and PAF-R. CD45 (top), CD68 (middle) and PAF-R (bottom) immunostaining results in stroma, as assessed by image analysis (top) and manual scoring (middle, bottom) in cervical samples from controls (C) (n = 18), responders (R) (n = 13) and non-responders (NR) (n = 9). The "box-and-whisker plot" represents the median value with 50% of all data falling within the box. The whiskers extend to the 5th and 95th percentiles. Boxes with different letter designations are significantly different, p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2551600&req=5

Figure 1: Immunostaining results of CD45, CD68 and PAF-R. CD45 (top), CD68 (middle) and PAF-R (bottom) immunostaining results in stroma, as assessed by image analysis (top) and manual scoring (middle, bottom) in cervical samples from controls (C) (n = 18), responders (R) (n = 13) and non-responders (NR) (n = 9). The "box-and-whisker plot" represents the median value with 50% of all data falling within the box. The whiskers extend to the 5th and 95th percentiles. Boxes with different letter designations are significantly different, p < 0.05.
Mentions: Immunostaining of CD45 showed that there are less leukocytes in the NR group than in the responders (Figure 1, upper panel; Figure 2A–C), indicating that prostaglandin treatment, when successful, induces leukocyte influx. CD68 immunostaining (Figure 2M) showed no significant difference between groups (Figure 1, middle panel).

Bottom Line: Post term women could be divided into at least two subgroups, one where parturition is possible to induce by prostaglandins and one where it is not.Our aim was to study parameters in cervical biopsies in women with spontaneous delivery at term (controls) and compare to those that are successfully induced post term (responders), and those that are not induced (non-responders), by local prostaglandin treatment.The impaired leukocyte influx, as reflected by the reduced number of CD45 positive cells as well as decreased immunostaining of IL-8, PAF-R and MMP-9 in the non-responders, could be one explanation of the failed ripening of the cervix in post term women.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division for Reproductive Endocrinology, Q2:08, Karolinska University Hospital-Solna, Karolinska Institutet, Stockholm, Sweden. Lena.Sahlin@ki.se

ABSTRACT

Background: Prolonged pregnancies are associated with increased rate of maternal and fetal complications. Post term women could be divided into at least two subgroups, one where parturition is possible to induce by prostaglandins and one where it is not. Our aim was to study parameters in cervical biopsies in women with spontaneous delivery at term (controls) and compare to those that are successfully induced post term (responders), and those that are not induced (non-responders), by local prostaglandin treatment.

Methods: Stromal parameters examined in this study were the accumulation of leukocytes (CD45, CD68), mRNAs and/or proteins for the extracellular matrix degrading enzymes (matrix metalloproteinase (MMP)-2, MMP-8 and MMP-9), their inhibitors (tissue inhibitor of MMP (TIMP)-1 and TIMP-2), interleukin-8 (IL-8), the platelet activating factor-receptor (PAF-R), syndecan-1 and estrogen binding receptors (estrogen receptor (ER)alpha, ERbeta and G-coupled protein receptor (GPR) 30) as well as the proliferation marker Ki-67.

Results: The influx of leukocytes as assessed by CD45 was strongest in the responders, thereafter in the controls and significantly lower in the non-responders. IL-8, PAF-R and MMP-9, all predominantly expressed in leukocytes, showed significantly reduced immunostaining in the group of non-responders, while ERalpha and GPR30 were more abundant in the non-responders, as compared to the controls.

Conclusion: The impaired leukocyte influx, as reflected by the reduced number of CD45 positive cells as well as decreased immunostaining of IL-8, PAF-R and MMP-9 in the non-responders, could be one explanation of the failed ripening of the cervix in post term women. If the decreased leukocyte influx is a primary explanation to absent ripening or secondary, as a result of other factors, is yet to be established.

Show MeSH
Related in: MedlinePlus