A role for cytokines in early pregnancy.

Cytokines are expressed in a variety of cell types of the reproductive system, although in most instances their functions are not understood. There are, however, a few instances where a role in early pregnancy has been established. First, preimplantation conceptuses of ruminant ungulate species, such as cattle, sheep and goat, secrete a unique Type I interferon (IFN-tau). By mechanisms that are still unclear, IFN-tau prevents the destruction of the corpus luteum and hence ensures the continued production of progesterone which is essential for continuation of pregnancy. Most like the IFN-tau prevent lutcolysis by modulating the output of a luteolytic hormone, prostaglandin F2 alpha, from the uterus. Depsite this involvement in pregnancy, the IFN-tau possess similar antiproliferative and antiviral activities to other Type I IFN, 1 lambda e.g. IFN-alpha. There are 4-5 genes for IFN-tau in sheep and cattle whose promotor regions are highly conserved and distinct from those of other Type I IFN. These genens are not virally inducible and are expressed only in the trophectoderm (outer epithelium of the developing placenta) from the time of blastocyst hatching to implantation. Leukemia inhibitory factor (LIF) is a multi-functional cytokine which is expressed by uterine endometrium of pregnant mice around day 4 of pregnancy. Female mice lacking a functional LIF gene are fertile but their blastocysts fail to implant, strongly implicating the cytokine in maternal control of implantation. Colony stimulating factors (CSF) are a family of proteins (GM-CSF, CSF-1, G-CSF, and IL-3) that stimulate the cellular proliferation and induction of terminal differentiation of hemopoietic progenitor cells. CSF-1 is expressed in the uterine endometrium of the mouse and human during early pregnancy and its receptor, fms, is present on trophoblast. The osteopetrotic mouse, which represents a natural "knockout" of the CSF-1 gene, exhibits a low rate of fetal implantation and poor fetal viability. It seems likely that CSF-1 expression by the uterus influences growth and differentiation of the placenta. Although different species may utilize different strategies for ensuring developmental and endocrinological coordination between the embryo and the mother, these three examples illustrate that cytokines are likely to be major participants as autocrine factors that direct the events of early pregnancy and not simply as modulators of the maternal immune system.

Gonadotropin releasing hormone in first trimester human placenta: Isolation, partial characterisation and in vitro biosynthesis.

Using a specific radioimmunoassay for gonadotropin releasing hormone, the presence of gonadotropin releasing hormone like material in the first trimester human placenta has been demonstrated. The material has been partially characterized using carboxy methyl cellulose chromatography, high pressure gel permeation chromatography and reverse phase C18 high pressure liquid chromatographic analysis. Analysis for bioactivity revealed that placental gonadotropin releasing hormone is much more active than synthetic gonadotropin releasing hormone in in vitro rat pituitary lutinising hormone release assay. In vitro biosynthetic studies using labelled precursors and immunoaffinity chromatography indicated that first trimester human placenta synthesizes gonadotropin releasing hormone like material.

Plasma levels of gonadotropin releasing hormone during menstrual cycle of Macaca radiata.

Α sensitive radioimmunoassay for gonadotropin releasing hormone has been developed. The assay has been validated for its specificity by testing various analogues of gonadotropin releasing hormone. Analysis of plasma samples during the menstrual cycle of 4 female bonnet monkeys showed a significant increase in the immunoreactive gonadotropin releasing hormone levels during preovulatory period of the menstrual cycle.

Studies on regulation of chorionic gonadotropin secretion in primates.

The regulation of secretion of chorionic gonadotropin in primates has been studied using both in vivo and in vitro models. In vivo studies using the pregnant bonnet monkey revealed that at the doses tested, the administration of progesterone or estradiol 17β in combination or alone did not result in any appreciable change in the duration or magnitude of serum chorionic gonadotropin levels. However, administration of lutropin-releasing hormone by intravenous route resulted in significant increase in chorionic gonadotropin levels within 30–60 min and the extent of stimulation seemed to depend on the state of pregnancy. For in vitro studies, explants or cells prepared from first trimester human placenta has been used. The functional integrity of these cells has been established by demonstrating the binding of [125I]- labelled human chorionic gonadotropin antibody to the cells as well as the synthesis of [3H]- labelled human chorionic gonadotropin. In vitro studies using the cells revealed that addition of lutropin-releasing hormone caused a significant increase in chorionic gonadotropin and estradiol 17 β secreted into the medium. Thus both in vivo and in vitro results suggest that lutropin-releasing hormone could be one of the factors involved in regulation of chorionic gonadotropin secretion in primates.