Myometrial Responses to Beta-Adrenoceptor Antagonists in Gynecological Malignancies

Objective: The aim of the study was to determine the influence of beta-adrenoceptor (ADRB) antagonists on contractile activity of the nonpregnant human uterus in patients affected by gynecological malignancies. Design: This was a controlled and prospective ex vivo study. Setting: The work was conducted as a collaboration between 4 academic departments. Materials and Methods: Myometrial specimens were obtained from women undergoing hysterectomy for benign gynecological disorders (reference group; N = 15), and ovarian (N = 15), endometrial (N = 15), synchronous ovarian-endometrial (N = 3), and cervical cancer (N = 10). Contractions of myometrial strips in an organ bath before and after applications of ADRB antagonists (propranolol, bupranolol, SR 59230A, and butoxamine) were studied under isometric conditions. Results: Propranolol and bupranolol attenuated contractions in the endometrial and cervical cancer groups similar to that in the reference group (all p < 0.05), whereas opposite effects were observed in the ovarian and synchronous ovarian-endometrial cancer groups. SR 59230A and butoxamine significantly increased contractions in the ovarian cancer group (both p < 0.001). Limitations: These results require now to be placed into a firm clinical context. Conclusions: Our study indicates that ovarian cancer considerably alters contractile activity of the nonpregnant human uterus in response to ADRB antagonists. This suggests a pathogenetic role of beta-adrenergic pathways in this malignancy. Furthermore, propranolol and bupranolol substantially influence spontaneous uterine contractility.

Maternal Cripto is required for proper uterine decidualization and peri-implantation uterine remodeling

Cripto encodes for a cell surface receptor whose role in embryonic development and stem cell maintenance has been studied. Cripto mRNA and protein have been detected in the human uterus at all stages of the menstrual cycle. To date, there is not much known about Cripto’s role in female reproduction. As Cripto null Knockout (KO) is embryonic lethal, we created a conditional KO (cKO) mouse model in which Cripto is deleted only in the reproductive tissues using a Cre-loxP system. Pregnancy rate and number of pups per litter were evaluated as general fertility indices. We observed a significant decrease in pregnancy rate and litter size with loss of uterine Cripto indicating that Cripto cKO females are subfertile. We showed that although the preimplantation period is normal in Cripto cKO females, 20% of cKO females fail to establish pregnancy and an additional 20% of females undergo full litter loss after implantation between day 5.5 postcoitum (d5.5pc) and d8.5pc. We showed that subfertility caused by loss of uterine Cripto is due to defects in uterine decidualization, remodeling, and luminal closure and is accompanied by significant downregulation of Bmp2, Wnt4 and several components of Notch signaling pathway which all are known to be important factors in uterine remodeling and decidualization. Our study demonstrates that Cripto is expressed in the uterus during critical stages of early pregnancy and its deletion results in subfertility due to implantation failure, impaired peri-implantation uterine remodeling and impaired uterine decidualization.

Human Uterus Transplantation from Living and Deceased Donors: The Interim Results of the First 10 Cases of the Czech Trial

Introduction: Uterus transplantation (UTx) is a rapidly evolving treatment of uterine-factor infertility. We report the results of the first 10 UTx procedures performed at our institution. Methods: The program started in April 2016 as a two-arm study comparing the efficacy of UTx from live donors (LD) and deceased donors (DD). Results: Between April 2016 and April 2018, we performed five DD UTx and five LD UTx. Two grafts had to be removed early due to thrombosis. One graft was removed due to chronic rejection and previous herpes simplex infection at month 7. Graft survival is 70% at one year. Recipient survival is 100% at two years. Live donor survival is 100% at three years. Three live-births have been achieved, two from a LD and one from a graft from a nulliparous DD. Vaginal anastomotic stenosis occurred in 63% (5/8) of grafts. Self-expanding stents have shown preliminary suitability for the treatment of vaginal stenosis. Three recipients developed severe acute rejection. Conclusion: The interim results of our study demonstrate mid-term viability in 70% of grafts. The LD UTx produced two live births and the DD UTx produced one live birth. Nulliparous donors should be considered for donation.

F. Westemark. Experimentelle Untersuchungen über die Wehenthätigkeit des menschlichen Uterus bei der physiologischen Geburt. (Skandinavisches Arch. für Physiologie. 1893). The forced activity of the human uterus during physiological childbirth. Experimental research

Westermark's article is divided into five chapters with a historical introduction. In the last day, the works of Schatz [1]), Poullet [2]), Polaillon [3]), Acconci [4]), Dhnhoffа [5]). [1] Arch. f. Gynk. 1872. Bd. III, p. 58. [2] Archives de Tocologie. Fvrier 1880. [3] Arch. de Physiologie 1880, p. 1.

Human Uterine Biopsy: Research Value and Common Pitfalls

The human uterus consists of the inner endometrium, the myometrium, and the outer serosa. Knowledge of the function of the uterus in health and disease is relevant to reproduction, fertility, embryology, gynaecology, endocrinology, and oncology. Research performed on uterine biopsies is essential to further the current understanding of human uterine biology. This brief review explores the value of the uterine biopsy in gynaecological and human fertility research and explores the common problems encountered when analysing data generated from different types of uterine biopsies, with the aim of improving the quality, reproducibility, and clinical translatability of future research.