Stage-variations of anandamide hydrolase activity in the mouse uterus during the natural oestrus cycle

Recent studies have demonstrated that the endogenous cannabinoids are important modulators of fertility in mammals. In particular, a role of the endocannabinoid system in early stages of embryo development, oviductal transport of embryos, pregnancy maintenance and labour has been demonstrated in rodents and/or in humans. In the present paper, we report the analysis of FAAH activity and protein content in the mouse uterus as a function of the natural oestrus cycle stages. Variations of FAAH activity are discussed in relationship to changes in sex steroid levels and to the possible action of AEA on remodelling of uterine tissues

Peri-implantation embryopathy induced by maternal diabetes.

Almost 10 years ago, it was proposed that the packaging of all devices and supplies used by diabetic patients for routine care should carry this warning label: 'Poor control of diabetes may cause birth defects. See your physician before becoming pregnant'. The present article reviews the evidence supporting the hypothesis that in mouse and rat experimental models, maternal pre-conceptional diabetes induces severe developmental alterations in embryos before and at implantation. The review (i) summarizes observations on embryos exposed to maternal diabetes in utero, (ii) summarizes data obtained by culturing embryos in vitro in the presence of high concentrations of D-glucose, (iii) discusses the possibility that alterations in the release of cytokines and growth factors by uterine cells contribute to early embryopathy and (iv) summarizes the evidence that apoptosis, a process of normal embryonic development, may be disrupted in blastocysts exposed to diabetic conditions in vivo and in vitro

Dysregulation of the cytokine network in the uterus of the diabetic rat.

Insulin-dependent (type I) diabetes is an auto-immune disorder that produces secondary complications in numerous non-immunological systems. Changes in the synthesis and action pattern of several cytokines have been associated with the development of these alterations. Based on the clinical facts that the pregnant and non-pregnant functions of the reproductive system are also disrupted by diabetes, our laboratory has decided to concentrate its research activities on the hypothesis that cytokines may be implicated in the uteropathy and embryopathy associated with the metabolic disorder. This review article summarizes our major findings concerning the synthesis of TNF-alpha and IL-1beta in the uterus of diabetic rats, and in cultures of rodent uterine cells upon their exposure to high concentrations of glucose. The paper also reviews evidence that both the peri-implanting embryo and the epithelial cell layer lining the uterine lumen are targets for the deleterious influence of excess TNF-alpha. If confirmed in the uterus of diabetic patients, these observations may explain how cytokines contribute to the dysregulation of crucial reproductive events like menstruation and embryo implantation in humans

Apoptosis in rodent peri-implantation embryos: differential susceptibility of inner cell mass and trophectoderm cell lineages--a review.

Inner cell mass (ICM) and trophectoderm cell lineages diverge early in cleavage in response to a complex combination of cellular and molecular determinative events. The resulting differences in metabolic requirements, cell positioning and micro-environments are considered as some of the major causes underlying the differential sensitivity of ICM and trophectoderm cell lines to embryotoxic agents. In most instances, ICM cells appear less resistant to disruption than trophectoderm cells, and past observations suggest that over-stimulation of apoptosis is probably one of the mechanisms leading to selective ICM depletion at the blastocyst stage. Disproportionate deficiency in this lineage below a certain threshold level may then prevent the ICM core from providing sufficient prefetal stem cells during gastrulation and from sending regulatory signals to the trophectoderm, leading to compromised post-implantation development. The aim of this review article is to discuss the above observations and to show the value of the impact of hyperglycaemia on blastocyst metabolism and development as an exciting model for further studies

Apoptosis at the time of embryo implantation in mouse and rat.

The aim of this review is to summarize the information currently available regarding the occurrence of apoptosis in the developing embryo and in the receptive uterus during the peri-implantation period of gestation. Cell death is detected in the inner cell mass of late pre-implantation embryos as the result of an eliminative process that helps trim the embryonic cell lineages of surplus or dysfunctional stem cells. Cell death is also detected in the epiblastic core of early post-implantation embryos, where the process is implicated in the formation of the pro-amniotic cavity. On the maternal side, uterine epithelial cells situated around the attachment site undergo cell death during the initial phase of implantation in order to facilitate embryo anchorage and access to maternal blood supply. Uterine stromal cells closest to the implantation chamber first transform into decidual cells and then commit suicide to make room for the rapidly growing embryo. Although apoptosis is well recognized as a crucial determinant of successful peri-implantation development, our understanding of the cellular and molecular mechanisms regulating this process clearly lags behind the comprehension of cell death control in other systems

Inhibin and activin production and subunit expression in human placental cells cultured in vitro.

Inhibins and activins are dimeric proteins, with each subunit being one of three related protein subunits (alpha, betaA or betaB). The mRNA levels of these subunits were studied quantitatively during in-vitro differentiation of human cytotrophoblast cells into syncytium, using Northern blot analysis and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. The corresponding protein concentrations were determined by specific enzyme-linked immunosorbent assays for inhibin A, B, pro alphaC and activin A in cellular protein extracts and culture medium (n = 5). Immunofluorescence studies showed syncytium formation after 48 h. The alpha subunit was present before plating and increased at 48 h (P<0.001) while the betaA subunit was weak before plating and increased at 24 h. The betaB subunit was not detected. With respect to corresponding protein synthesis, inhibin A (alpha + betaA) had risen after 48 h in cellular protein extract and after 72 h in culture medium, while activin A (betaA + betaB) was detected after 24 h, with no significant variations in culture medium. There was a good correlation between inhibin A and alpha subunit expression (r = 0.736, P<0.001), as well as between activin A and betaA subunit expression (r = 0.755, P<0.001). This study showed that mRNA expression parallels protein synthesis of inhibin and activin in trophoblast cells. Inhibin A synthesis appears to be dependent on alpha subunit mRNA expression, rather than on the betaA subunit which controls activin A synthesis. This study has also shown that isolated cytotrophoblast cells do not produce dimeric inhibin. However, during the transformation of cytotrophoblast cells into syncytium, betaA subunit mRNA expression may be an indicator of cell aggregation, while alpha subunit mRNA expression may be an indicator of cell fusion