Ultrastructural cilia defects in multi-ciliated uterine glandular epithelial cells from women with reproductive failure

Author:

Pearson-Farr Jennifer E1,Doherty Regan23,Chatelet David S2,Goggin Patricia23,Ng Ka Ying Bonnie1,Lucas Jane S34,Cleal Jane K15,Cheong Ying C16ORCID,Lewis Rohan M15ORCID

Affiliation:

1. Human Development and Health, University of Southampton, Faculty of Medicine, Southampton, UK

2. Biomedical Imaging Unit, Faculty of Medicine, University of Southampton, Southampton, UK

3. Primary Ciliary Dyskinesia Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK

4. School of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton, UK

5. Institute for Life Sciences, University of Southampton, Highfield, Southampton, UK

6. Complete Fertility Centre Southampton, Princess Anne Hospital, Southampton, UK

Abstract

In brief The causes of subfertility and recurrent pregnancy loss are often unclear. This study shows that endometrial gland cilia from women with subfertility have ultrastructural defects. Abstract Endometrial glands secrete products into the endometrium and are necessary for embryo implantation and successful pregnancy. However, structural and functional abnormalities in endometrial gland cilia from women with reproductive failure remain poorly understood. This was a cross-sectional study where endometrial biopsies were collected at days 19–23 of the menstrual cycle from women with unexplained recurrent pregnancy loss (n = 15), unexplained subfertility (n = 11) or from egg donor control participants (n = 10). Endometrial gland cilia ultrastructure was imaged by transmission electron microscopy and cilia defects assessed by an electron-microscopist from a national primary ciliary dyskinesia diagnostic centre. Endometrial glands were isolated, and the cilia beat frequency recorded by high speed video. Subfertile women have proportionately lower ultrastructurally normal cilia (P < 0.05); higher frequency of absent dynamin arms (P < 0.01) or inner arm defects (P < 0.01) and lower cilia beat frequency (P < 0.05). The mechanisms underlying these obversions have yet to be determined. Recent studies have identified cilia related gene expression changes associated with reproductive failure and this study adds to the growing body of literature revealing structural and functional changes. The observation that cilia defects occurred at a higher frequency in endometrial glands of subfertile women raises the question of its mechanistic role in implantation.

Publisher

Bioscientifica

Subject

Cell Biology,Obstetrics and Gynecology,Endocrinology,Embryology,Reproductive Medicine

Reference21 articles.

1. Mutations in CCDC39 and CCDC40 are the major cause of primary ciliary dyskinesia with axonemal disorganization and absent inner dynein arms;Antony,2013

2. Human endometrium ultrastructure during the implantation window: a new perspective of the epithelium cell types;Bartosch,2011

3. The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality;Boskovski,2013

4. Risk factors for ectopic pregnancy: a comprehensive analysis based on a large case-control, population-based study in France;Bouyer,2003

5. Environmental pollutants damage airway epithelial cell cilia: implications for the prevention of obstructive lung diseases;Cao,2020

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