Endometrium-derived organoids from cystic fibrosis patients and mice as new models to study disease-associated endometrial pathobiology DOI Creative Commons
Ellen De Pauw, Beau Gommers, Marjolein M. Ensinck

et al.

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: March 13, 2025

Cystic fibrosis (CF) is a life-shortening genetic disorder, caused by mutations in the CF transmembrane conductance regulator (CFTR) protein that regulates ion and fluid transport epithelial tissue. Female patients face considerable fertility challenges, with higher prevalence of deficient compared to healthy women. Not much known about underlying causes. In particular, pathobiology endometrium, uterus' inner lining essential for pregnancy expressing fluctuating CFTR levels during menstrual cycle, unexplored CF. To address this gap, we developed organoid models from patient endometrium. The organoids recapitulated characteristics revealed molecular pathway differences cycle-recapitulating hormone responses endometrial organoids. Furthermore, specific functional aberrations were restored modulator treatment. further complement human unraveling CF, also mouse model found recapitulate characteristics. Moreover, single-cell RNA-sequencing analysis uterus traits endometrium similar (as evidenced its model). Our study provides new advance our understanding CF-associated pathobiology, particularly regarding cycle impact fertility. This research timely since improved therapeutics result increased life expectancy, allowing more consider starting family.

Language: Английский

Autophagy and Female Fertility: Mechanisms, Clinical Implications, and Emerging Therapies DOI Creative Commons
Abdel Halim Harrath, Md. Ataur Rahman,

Sujay Kumar Bhajan

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(16), P. 1354 - 1354

Published: Aug. 14, 2024

Autophagy, an evolutionarily conserved cellular mechanism essential for maintaining internal stability, plays a crucial function in female reproductive ability. In this review, we discuss the complex interplay between autophagy and several facets of health, encompassing pregnancy, ovarian functions, gynecologic malignancies, endometriosis, infertility. Existing research emphasizes significance embryo implantation, specifically endometrium, highlighting its necessity ensuring proper fetal development. Although some knowledge has been gained, there is still lack on specific molecular impacts quality oocytes, growth follicles, general health. Autophagy role maturation, quality, development oocytes. It also involved aging, contributing to reductions that occur with age. This review explores physiological functions system, participation toxicity, important connections endometrium embryo. addition, study investigates possibility emerging treatment approaches aim modify autophagy, using both natural substances synthetic molecules, improve fertility outcomes. Additionally, intends inspire future exploration into intricate health by reviewing recent studies pinpointing areas where current lacking. Subsequent investigations should prioritize conversion these discoveries practical uses medical field, which could potentially result groundbreaking therapies infertility other difficulties related reproduction. Therefore, gaining comprehensive understanding many effects would not only further field biology but open new possibilities diagnostic methods.

Language: Английский

Citations

5
Extracellular matrix and pregnancy: functions and opportunities caught in the net DOI Creative Commons

Francesca Rossi,

Stefania Luppi, Albina Fejza

et al.

Reproductive Biology and Endocrinology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 14, 2025

The extracellular matrix is a complex network of macromolecules that support the growth and homeostatic development organisms. By conveying multiple signaling cascades, it impacts on several biological processes influences behaviour numerous cell types. During endometrial cycle key events necessary for correct embryo implantation placentation, this bioactive meshwork substantially modified to favour receptivity vascular adaptation, trophoblast migration, immune activation as well. A remodeling fundamental establishment physiological pregnancy; indeed, occurrence altered modifications associates with gestational disorders such preeclampsia. In present review, we will critically evaluate role pivotal constituents in regulating steps provide up-to-date information concerning their primary mechanisms action discuss potential novel source biomarkers therapeutic targets.

Language: Английский

Citations

0
Endometrium-derived organoids from cystic fibrosis patients and mice as new models to study disease-associated endometrial pathobiology DOI Creative Commons
Ellen De Pauw, Beau Gommers, Marjolein M. Ensinck

et al.

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: March 13, 2025

Cystic fibrosis (CF) is a life-shortening genetic disorder, caused by mutations in the CF transmembrane conductance regulator (CFTR) protein that regulates ion and fluid transport epithelial tissue. Female patients face considerable fertility challenges, with higher prevalence of deficient compared to healthy women. Not much known about underlying causes. In particular, pathobiology endometrium, uterus' inner lining essential for pregnancy expressing fluctuating CFTR levels during menstrual cycle, unexplored CF. To address this gap, we developed organoid models from patient endometrium. The organoids recapitulated characteristics revealed molecular pathway differences cycle-recapitulating hormone responses endometrial organoids. Furthermore, specific functional aberrations were restored modulator treatment. further complement human unraveling CF, also mouse model found recapitulate characteristics. Moreover, single-cell RNA-sequencing analysis uterus traits endometrium similar (as evidenced its model). Our study provides new advance our understanding CF-associated pathobiology, particularly regarding cycle impact fertility. This research timely since improved therapeutics result increased life expectancy, allowing more consider starting family.

Language: Английский

Citations

0