The ovary is perhaps the most dynamic organ in the human body, only rivaled by the uterus. The molecular mechanisms that regulate follicular growth and regression, ensuring ovarian tissue homeostasis, remain elusive. We have performed single-cell RNA-sequencing using human adult ovaries to provide a map of the molecular signature of growing and regressing follicular populations. We have identified different types of granulosa and theca cells and detected local production of components of the complement system by (atretic) theca cells and stromal cells. We also have detected a mixture of adaptive and innate immune cells, as well as several types of endothelial and smooth muscle cells to aid the remodeling process. Our results highlight the relevance of mapping whole adult organs at the single-cell level and reflect ongoing efforts to map the human body. The association between complement system and follicular remodeling may provide key insights in reproductive biology and (in)fertility.

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BackgroundIn society, there is a clear need to improve the success rate of techniques to restore fertility. Therefore a deeper knowledge of the dynamics of the complex molecular environment that regulates human gametogenesis and (early) folliculogenesis in vivo is necessary. Here, we have studied these processes focusing on the formation of the follicular basement membrane (BM) in vivo.ResultsThe distribution of the main components of the extracellular matrix (ECM) collagen IV, laminin and fibronectin by week 10 of gestation (W10) in the ovarian cortex revealed the existence of ovarian cords and of a distinct mesenchymal compartment, resembling the organization in the male gonads. By W17, the first primordial follicles were assembled individually in that (cortical) mesenchymal compartment and were already encapsulated by a BM of collagen IV and laminin, but not fibronectin. In adults, in the primary and secondary follicles, collagen IV, laminin and to a lesser extent fibronectin were prominent in the follicular BM.ConclusionsThe ECM-molecular niche compartimentalizes the female gonads from the time of germ cell colonization until adulthood. This knowledge may contribute to improve methods to recreate the environment needed for successful folliculogenesis in vitro and that would benefit a large number of infertility patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12861-015-0054-0) contains supplementary material, which is available to authorized users.

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Objective. To evaluate the clinical relevance of 3-dimensional saline infusion sonography (3D-SIS) in addition to conventional SIS in women with abnormal uterine bleeding suspected of having intrauterine abnormalities. Methods. All women suspected of having intrauterine abnormalities were eligible. Before 3D-SIS, conventional SIS was performed. The results of these techniques were compared with the "combined method reference standard" (hysteroscopy, endometrial sampling, and clinical followup in cases with normal SIS findings). Diagnostic characteristics (with 95% confidence intervals [CIs]) of 3D-SIS and SIS were calculated as well as their respective accuracy in evaluating the histologic nature, the intrauterine extension, and the location of intrauterine abnormalities. Moreover, the reliability (κ value) and clinical relevance of 3D-SIS were assessed. Results. A total of 49 women were included, and 4 women were excluded. The positive predictive values of 3D-SIS and SIS were, respectively, 1.00 and 0.86 (95% CI, 0.72-0.99; P = .15), and the diagnostic accuracy values were 0.98 (95% CI, 0.94-1.0) and 0.91 (95% CI, 0.83-0.99; P = .08). Saline infusion sonography and 3D-SIS were equally accurate in evaluating the histologic nature, intrauterine extent, and location of intrauterine abnormalities (respective κ values: 0.85 versus 0.93; P = .88; 0.83 versus 0.83; and 0.77 versus 0.80; P = .81). The reliability of 3D-SIS was good: intraobserver and interobserver agreement (κ) were 0.78 and 0.72. Three women (6.7%) had the benefit of additional 3D-SIS: in these women, SIS wrongly led to a diagnosis of intrauterine abnormalities (P = .08). Conclusions. Three-dimensional saline infusion sonography is valid and reliable in women suspected of having intrauterine abnormalities and may indeed have relevant clinical value in addition to conventional SIS.