No abstract

Chromosome errors, or aneuploidy, affect an exceptionally high number of human conceptions, causing pregnancy loss and congenital disorders. Here, we have followed chromosome segregation in human oocytes from females aged 9 to 43 years and report that aneuploidy follows a U-curve. Specific segregation error types show different age dependencies, providing a quantitative explanation for the U-curve. Whole-chromosome nondisjunction events are preferentially associated with increased aneuploidy in young girls, whereas centromeric and more extensive cohesion loss limit fertility as women age. Our findings suggest that chromosomal errors originating in oocytes determine the curve of natural fertility in humans.

Uterine fibroids (UFs) are benign tumors of the female genital tract made of the smooth muscle of the uterus. UF growth depends mostly on the influence of the steroid hormones and selected growth factors. Transforming growth factor β (TGF-βs) is a polypeptide that consists of three isoforms: TGF-β1, TGF-β2, and TGF-β3. At present, TGF-β is considered to be one of the key factors in the pathophysiology of UFs. It plays a major role in cellular migration within the tumor, stimulates tumor growth, and enhances tumor metabolism. As a consequence of various dependencies, the synthesis and release of TGF-β in a UF tumor is increased, which results in excessive extracellular matrix production and storage. High concentrations or overexpression of TGF-β mediators may be responsible for clinically symptomatic UFs. The aim of this review was to check the available evidence for the influence of the TGF-β family on UF biology. We conducted their search in PubMed of the National Library of Medicine with the use of the following selected keywords: “uterine fibroid”, “leiomyoma”, and “transforming growth factor β”. After reviewing the titles and abstracts, more than 115 full articles were evaluated. We focused on the TGF-β-related molecular aspects and their influence on the most common symptoms that are associated with UFs. Also, we described how the available data might implicate the current medical management of UFs.

Data availability: All data are available at dbGaP (study #35769) under appropriate Data Use Certification (DUC) agreement in accordance with Danish ethical regulation and General Data Protection Regulation (GDPR).