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Veronica Astro Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia

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Elisabetta Fiacco Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia

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Kelly Johanna Cardona-Londoño Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia

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Ilario De Toma Sequentia Biotech SL, Barcelona, Spain

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Hams Saeed Alzahrani Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

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Jumana Alama Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia

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Amal Kokandi Department of Dermatology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

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Taha Abo-Almagd Abdel-Meguid Hamoda Department of Urology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

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Majed Felemban Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
Center of Innovation in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

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Antonio Adamo Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia

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Objective

The transcriptional landscape of Klinefelter syndromeduring early embryogenesis remains elusive. This study aimed to evaluate the impact of X chromosome overdosage in 47,XXY males induced pluripotent stem cells (iPSCs) obtained from patients with different genomic backgrounds and ethnicities.

Design and method

We derived and characterized 15 iPSC lines from four Saudi 47,XXY KS patients and one Saudi 46,XY male. We performed a comparative transcriptional analysis using the Saudi KS-iPSCs and a cohort of European and North American KS-iPSCs.

Results

We identified a panel of X-linked and autosomal genes commonly dysregulated in Saudi and European/North American KS-iPSCs vs 46,XY controls. Our findings demonstrate that seven PAR1 and nine non-PAR escape genes are consistently dysregulated and mostly display comparable transcriptional levels in both groups. Finally, we focused on genes commonly dysregulated in both iPSC cohorts and identified several gene-ontology categories highly relevant to KS physiopathology, including aberrant cardiac muscle contractility, skeletal muscle defects, abnormal synaptic transmission, and behavioral alterations.

Conclusions

Our results indicate that a transcriptomic signature of X chromosome overdosage in KS is potentially attributable to a subset of X-linked genes sensitive to sex chromosome dosage and escaping X inactivation, regardless of the geographical area of origin, ethnicity, and genetic makeup.

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Theodoros Karampitsakos Third Department of Obstetrics and Gynecology, ATTIKON University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
Unit of Endocrinology, Diabetes Mellitus and Metabolism, ARETAIEION University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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Fotini Kanouta Unit of Endocrinology, Diabetes Mellitus and Metabolism, First Department of Obstetrics and Gynecology, ALEXANDRA University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
Unit of Endocrinology, Diabetes Mellitus and Metabolism, ARETAIEION University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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Christos Chatzakis Second Department of Obstetrics and Gynecology, IPPOKRATEIO General Hospital of Thessaloniki, Aristotle, University of Thessaloniki, Athens, Greece

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Vassilios Bakoulas Athens, Greece

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Alexandros Gryparis Department of Speech and Language Therapy, University of Ioannina, Ioannina, Greece
Unit of Endocrinology, Diabetes Mellitus and Metabolism, ARETAIEION University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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Petros Drakakis Third Department of Obstetrics and Gynecology, ATTIKON University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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Djuro Macut Department of Endocrinology, Diabetes and Diseases of Metabolism, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Unit of Endocrinology, Diabetes Mellitus and Metabolism, ARETAIEION University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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George Mastorakos Unit of Endocrinology, Diabetes Mellitus and Metabolism, ARETAIEION University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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Introduction

To investigate whether synthetic (s) glucocorticoids (GCs) administered between the 24th and the 34th gestational weeks in pre-term labor might precipitate labor, studies on sGCs administration were reviewed. The physiology of endogenous glucocorticoid-related increase in fetal–maternal circulation and its association with labor, followed by a scoping review of studies on exogenous sGCs administered for fetal lung maturation and the timing of labor, were included.

Materials and methods

The methodology of systematic reviews was followed. MEDLINE, Cochrane Library, and Google Scholar databases were searched until October 2023, for original studies investigating the administration of sGCs in pregnancies risking pre-term labor. Duplicates were removed, and 1867 abstracts were excluded as irrelevant. Six controlled and four non-controlled studies were included. The index group consisted of 6001 subjects and 7691 controls in the former, while in the latter, the index group consisted of 2069 subjects.

Results

In three out of the six controlled studies, gestational age at labor was significantly lower in sGC-treated women than in controls, while in three studies, gestational age at labor was lower in sGC-treated women than in controls, with a trend toward statistical significance. In one study, gestational age at labor was significantly lower in controls than in sGC-treated women. In the non-controlled studies, the majority of women delivered less than 1 week from the day of sGC administration.

Conclusions

In this scoping review, studies lack homogeneity. However, in the controlled studies, a pattern of earlier labor emerges among sGC-treated pregnant women. The use of multiple courses of antenatal sGCs appears to be associated with precipitated labor. Their use should be carefully weighed. Carefully designed trials should examine this ongoing scientific query.

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Charissa van Zwol-Janssens Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Aglaia Hage Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Kim van der Ham Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Birgitta K Velthuis Department of Radiology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands

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Ricardo P J Budde Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands

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Maria P H Koster Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Arie Franx Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Bart C J M Fauser Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht & University of Utrecht, Utrecht, the Netherlands

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Eric Boersma Department of Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Daniel Bos Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Joop S E Laven Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Yvonne V Louwers Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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the CREW consortium
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the CREW consortium

Besides age, estrogen exposure plays a crucial role in changes in bone density (BD) in women. Premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS) are conditions in reproductive-aged women in which the exposure to estrogen is substantially different. Women with a history of preeclampsia (PE) are expected to have normal estrogen exposure. Within the CREw-IMAGO study, we investigated if trabecular BD is different in these women because of differences in the duration of estrogen exposure. Trabecular BD was measured in thoracic vertebrae on coronary CT scans. Women with a reduced estrogen exposure (POI) have a lower BD compared to women with an intermediate exposure (PE) (mean difference (MD) −26.8, 95% CI −37.2 to −16.3). Women with a prolonged estrogen exposure (PCOS) have the highest BD (MD 15.0, 95% CI 4.3–25.7). These results support the hypothesis that the duration of estrogen exposure in these women is associated with trabecular BD.

Significance statement

Our results suggest that middle-aged women with PCOS have a higher BD and women with POI have a lower BD. We hypothesized that this is due to either a prolonged estrogen exposure, as seen in women with PCOS, or a reduced estrogen exposure, as in women with POI. In the counseling of women with reproductive disorders on long-term health issues, coronary CT provides a unique opportunity to assess both coronary artery calcium score for cardiovascular screening as well as trabecular BD.

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