Progestins are successfully used in the treatment of endometriosis; however, the exact mechanisms of their action are still unsolved. We here focused on the effect of different progestins on parameters of extracellular matrix degradation and angiogenesis involved in the establishment and maintenance of ectopic endometrial lesions. Human endometrium was intraperitoneally transplanted into nude mice. After 7 and 28 days of treatment with progesterone, dydrogesterone, or its metabolite dihydrodydrogesterone, respectively, ectopic lesions were evaluated for proliferation and apoptosis. Expression of estrogen receptor α, progesterone receptor-AB, the angiogenetic factors, cysteine-rich angiogenic inducer (CYR61), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGFA) and the matrix metalloproteinase (MMP)-2, -3, -7 and -9 was investigated. Functional impact on angiogenesis was evaluated by density of microvessels and of vessels stabilized by pericytes within the ectopic lesions. Although dydrogesterone significantly reduced proliferation of endometrial stromal cells after 28 days, suppression of apoptosis was independent from progestins. Expression of MMP-2 was significantly reduced by all progestins and MMP-3 by dydrogesterone. In the grafted endometrial tissue, transcription of bFGF was suppressed by progesterone and dihydrodydrogesterone, and VEGFA and CYR61 by dihydrodydrogesterone and dydrogesterone. In parallel, microvessel density was slightly suppressed by progestins, whereas number of stabilized vessels increased. Thus, progestins regulate factors important for the establishment and maintenance of ectopic endometrial lesions.

Cell contacts exhibit a considerable influence on tissue physiology and homeostasis by controlling paracellular and intercellular transport processes, as well as by affecting signaling pathways. Since they maintain cell polarity, they play an important role in cell plasticity. The knowledge about the junctional protein families and their interactions has increased considerably during recent years. In contrast to most other tissues, the endometrium undergoes extensive physiological changes and reveals an extraordinary plasticity due to its crucial role in the establishment and maintenance of pregnancy. These complex changes are accompanied by changes in direct cell–cell contacts to meet the various requirements in the respective developmental stage. Impairment of this sophisticated differentiation process may lead to failure of implantation and embryo development and may be involved in the pathogenesis of endometrial diseases. In this article, we focus on the knowledge about the distribution and regulation of the different junctional proteins in the endometrium during cycling and pregnancy, as well as in pathologic conditions such as endometriosis and cancer. Decoding these sophisticated interactions should improve our understanding of endometrial physiology as well as of the mechanisms involved in pathological conditions.

Maternal effect genes code for oocyte proteins that are important for early embryogenesis. Transcription in oocytes does not take place from the onset of meiotic progression until zygotic genome activation. During this period, protein levels are regulated posttranscriptionally, for example by poly(A) tail length. Posttranscriptional regulation may be impaired in preovulatory and postovulatory aged oocytes, caused by delayed ovulation or delayed fertilization, respectively, and may lead to developmental defects. We investigated transcript levels and poly(A) tail length of ten maternal effect genes in in vivo- and in vitro- (follicle culture) grown oocytes after pre- and postovulatory aging. Quantitative RT-PCR was performed using random hexamer-primed cDNA to determine total transcript levels and oligo(dT)₁₆-primed cDNA to analyze poly(A) tail length. Transcript levels of in vivo preovulatory-aged oocytes remained stable except for decreases in Brg1 and Tet3. Most genes investigated showed a tendency towards increased poly(A) content. Polyadenylation of in vitro preovulatory-aged oocytes was also increased, along with transcript level declines of Trim28, Nlrp2, Nlrp14 and Zar1. In contrast to preovulatory aging, postovulatory aging of in vivo- and in vitro-grown oocytes led to a shortening of poly(A) tails. Postovulatory aging of in vivo-grown oocytes resulted in deadenylation of Nlrp5 after 12 h, and deadenylation of 4 further genes (Tet3, Trim28, Dnmt1, Oct4) after 24 h. Similarly, transcripts of in vitro-grown oocytes were deadenylated after 12 h of postovulatory aging (Tet3, Trim28, Zfp57, Dnmt1, Nlrp5, Zar1). This impact of aging on poly(A) tail length may affect the timed translation of maternal effect gene transcripts and thereby contribute to developmental defects.

Purpose: To evaluate possible risks of strong static magnetic fields for embryo implantation, gestation, organogenesis, and embryonic development.Materials and Methods: Pregnant mice were exposed for 75 minutes daily during the entire course of pregnancy at the bore entrance, representing the position of medical staff, and at the isocenter, representing the position of patients, of a 1.5 T and a 7 T human MRI scanner.Results: No effect of static magnetic field strength was observed with regard to pregnancy rate, duration of pregnancy, litter size, still births, malformations, sex distribution, or postpartum death of offspring. During the first 8 weeks postnatal, mice exposed in utero to a magnetic field strength of 1.5 T or stronger showed a slight delay in weight gain and in time to eye opening compared to controls.Conclusion: Daily exposure to strong magnetic fields during pregnancy had no deleterious effect on offspring; however, a developmental retardation could be observed postnatally with regard to weight gain and eye opening. J. Magn. Reson. Imaging 2014;39:691–699. © 2013 Wiley Periodicals, Inc.

Although there is an apparent association between endometriosis and impaired fertility, the pathophysiology of the reduced fecundity in women with endometriosis still remains unclear. Reproduction is a complex and multifactorial process, and possible factors contributing to the reduced fertility of endometriosis patients include defective function of the ovary, gametes, and endometrium as well as developmental disorders of the embryo. Because controlled experiments in humans are limited due to ethical reasons, experimental animal models have been developed mainly in nonhuman primates and laboratory rodents by induction of endometriosis via autologous transplantation of endometrial tissue. Animals with induced endometriosis reveal an impairment of fecundity similar to the situation described for humans and have been used to identify effects of ectopic endometrial tissue on adhesion formation, peritoneal fluid composition, ovarian function, endometrial gene expression, and embryo implantation. These animal models of endometriosis yield a valuable tool to study the mechanisms of endometriosis-associated infertility especially during the onset of the disease that cannot be investigated in women.