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This Article Full Text Full Text (PDF) All Versions of this Article: 70/1/123    most recent biolreprod.103.018754v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal My Folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by White, C. A. Articles by Robertson, S. A. Search for Related Content PubMed PubMed Citation Articles by White, C. A. Articles by Robertson, S. A. Agricola Articles by White, C. A. Articles by Robertson, S. A.

Effect of Interleukin-10 Null Mutation on Maternal Immune Response and Reproductive Outcome in Mice¹

Department of Obstetrics and Gynaecology and Reproductive Medicine Unit,³ University of Adelaide, Adelaide 5005, Australia Louisiana State University/Tulane Gene Therapy Consortium,⁴ Louisiana State University Health Sciences Centre, New Orleans, Louisiana 70112

Interleukin-10 (IL-10) is an anti-inflammatory and immune-deviating cytokine expressed in the endometrium and placenta. IL-10 null mutant (IL-10-/-) mice have been employed to examine the role of IL-10 in regulating immune events in early pregnancy and its significance in implantation and pregnancy success. The inflammatory response elicited in endometrial tissue by insemination was amplified in IL-10-/- mice, with a 66% increase in leukocytes in the endometrial stroma on Day 3 of pregnancy. Despite this, no evidence of abnormal type 1/type 2 skewing was seen in T-lymphocytes from lymph nodes draining the uterus. On Day 18 of gestation, IL-10-/- females mated with IL-10-/- males had 15% more implantation sites and 27% more viable fetuses than pregnant wild-type (IL-10+/+) mice. Placental weight was unaffected, but fetal weight and the fetal:placental weight ratio were higher in IL-10-/- pregnancies. Similar data were obtained in allogeneic pregnancies when IL-10-/- females were mated with major-histocompatibility complex (MHC) disparate IL-10-/- males. Pups delivered by IL-10-/- mothers had increased birth weight and followed an altered growth trajectory, with growth impairment evident from early postnatal life into adulthood, which was reflected in alterations in body composition at 14 wk of age. This study shows that although IL-10 is not essential for maternal immune tolerance or successful pregnancy irrespective of MHC disparity in the fetus, maternal IL-10 is a determinant of growth trajectory in progeny in utero and after birth.

¹ Supported by project and fellowship grants from the NHMRC (Australia) and a project grant from the Pest Animal Control CRC (Australia).

² Correspondence: Sarah A. Robertson, Department of Obstetrics and Gynaecology, University of Adelaide, Adelaide, SA 5005 Australia. FAX: 618 8303 4099; sarah.robertson{at}adelaide.edu.au

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