Endometriosis currently affects ∼5.5 million reproductive-aged women in the U.S. with symptoms such as painful periods (dysmenorrhea), chronic pelvic pain, pain with intercourse (dyspareunia), and infertility. It is defined as the presence of endometrial tissue outside the uterine cavity and is found predominately attached to sites within the peritoneal cavity. Diagnosis for endometriosis is solely made through surgery as no consistent biomarkers for disease diagnosis exist. There is no cure for endometriosis and treatments only target symptoms and not the underlying mechanism(s) of disease. The nature of individual predisposing factors or inherent defects in the endometrium, immune system, and/or peritoneal cavity of women with endometriosis remains unclear. The literature over the last 5 years (2010-2015) has advanced our critical knowledge related to hormones, hormone receptors, immune dysregulation, hormonal treatments, and the transformation of endometriosis to ovarian cancer. In this review, we cover the aforementioned topics with the goal of providing the reader an overview and related references for further study to highlight the progress made in endometriosis research, while concluding with critical areas of endometriosis research that are urgently needed.

Purpose Diminished ovarian reserve (DOR) affects 10 % of women seeking fertility treatment. Although it is much more prevalent than premature ovarian failure, less is known about its etiology. The purpose of this article is to review the possible genetic causes of, and associations with, pathologic DOR.

Background: Endometriosis is a gynecological disease affecting 1 in 10 women of reproductive age. Endometriosis incidence has risen; however, whether this rise is due to disease awareness or environmental contamination is not known. Objective: The objective of this study was to determine if bisphenol A (BPA) or bisphenol AF (BPAF) potentiate the development of endometriosis and if hormonal status alters how toxicant exposure affects disease. Methods: A mouse model of endometriosis, where minced uterine tissue is injected into the peritoneal cavity of a host mouse, was used to examine the effects of BPA and BPAF on endometriosis lesion development in ovariectomized and hormonally intact mice. BPA and BPAF were delivered through diet to include no-observed-adverse-effect-level (NOAEL) and the low-observed-adverse-effect-level (LOAEL) exposure levels. After six weeks (at necropsy), lesions, ovaries, and blood were collected to examine characteristics, gene expression, and hormonal regulation. Results: BPA and BPAF treatments affected endometriosis in a manner specific to dose and hormonal status of the host mouse. Estrogen and endometriosis-mediated differences in lesion target gene expression also depended on hormonal status. In intact mice, ovarian steroidogenic pathways were disrupted, progesterone levels were lowered, and atretic oocyte numbers were higher with toxicant exposure. BPAF, more so than BPA, resulted in more endometriosis lesion growth, but both toxicants disrupted normal ovarian signaling. Conclusion: These findings further our understanding of the effects and hormonal impacts of BPA and BPAF on endometriosis perturbation in ovariectomized and hormonally intact mice. BPAF appeared to be similar if not more estrogenic than BPA and may be affecting an environmental contribution of the increased incidence of endometriosis. https://doi.org/10.1289/EHP3802

BackgroundThe Rho kinase pathway plays a key role in many early cell/tissue determination events that take place in embryogenesis. Rho and its downstream effector Rho kinase (ROCK) play pivotal roles in cell migration, apoptosis (membrane blebbing), cell proliferation/cell cycle, cell-cell adhesion and gene regulation. We and others have previously demonstrated that inhibition of ROCK blocks endoderm differentiation in embryonal carcinoma stem cells, however, the effect of ROCK inhibition on mesoderm and ectoderm specification has not been fully examined. In this study, the role of ROCK within the specification and differentiation of all three germ layers was examined.Methodology/Principal FindingsP19 cells were treated with the specific ROCK inhibitor Y-27623, and increase in differentiation efficiency into neuro-ectodermal and mesodermal lineages was observed. However, as expected a dramatic decrease in early endodermal markers was observed when ROCK was inhibited. Interestingly, within these ROCK-inhibited RA treated cultures, increased levels of mesodermal or ectodermal markers were not observed, instead it was found that the pluripotent markers SSEA-1 and Oct-4 remained up-regulated similar to that seen in undifferentiated cultures. Using standard and widely accepted methods for reproducible P19 differentiation into all three germ layers, an enhancement of mesoderm and ectoderm differentiation with a concurrent loss of endoderm lineage specification was observed with Y-27632 treatment. Evidence would suggest that this effect is in part mediated through TGF-β and SMAD signaling as ROCK-inhibited cells displayed aberrant SMAD activation and did not return to a ‘ground’ state after the inhibition had been removed.Conclusions/SignificanceGiven this data and the fact that only a partial rescue of normal differentiation capacity occurred when ROCK inhibition was alleviated, the effect of ROCK inhibition on the differentiation capacity of pluripotent cell populations should be further examined to elucidate the role of the Rho-ROCK pathway in early cellular ‘fate’ decision making processes.