In Utero Exposure to Glucocorticoids and Pubertal Timing in Sons and Daughters

Abstract

Early pubertal timing has been associated with adult diseases, and identifying preventable causes is of importance. In utero exposure to exogenous glucocorticoids, has been associated with changes in the reproductive hormonal axes in the children, which may influence pubertal timing. Exogenous glucocorticoids can be indicated for diseases such as asthma, allergy, skin diseases, as well as muscle and joint diseases. The aim was to explore the association between in utero exposure to glucocorticoids and pubertal timing in the children. This population-based study was conducted in the Puberty Cohort including 15,819 children, which is a sub-cohort of the Danish National Birth Cohort. Information on maternal glucocorticoid treatment was collected through interviews during pregnancy. Information on pubertal timing was obtained by questionnaires every 6 months throughout puberty, including Tanner Stages, axillary hair, acne, voice break, first ejaculation and menarche. The potential impact of confounding by indication was explored by stratifying on indication and treatment status. Overall, 6.8% of the children were exposed to glucocorticoids in utero. Exposure to glucocorticoids in utero was not associated with earlier puberty for neither boys nor girls with combined estimates of 0.4 months (95% CI: –1.5; 2.2) and –0.7 months (95% CI: –2.5; 1.2).

Life Course Impact of Glucocorticoids During Pregnancy on Muscle Development and Function

“…In addition to glucocorticoid synthesis that determines the critical window of fetal glucocorticoid exposure, glucocorticoid metabolism controls gradients, or concentration of glucocorticoid in the fetus. Two enzymes 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and 2 (11β-HSD2) play a primary role in glucocorticoid metabolism and are highly expressed in the uterus, placenta and fetal tissues ( Solano et al, 2016 ; Sand et al, 2019 ). The enzyme 11β-HSD1 primarily converts the inactive form of glucocorticoid 11-dehydrocorticosterone or cortisone to active form corticosterone in rodents or cortisol in human or livestock ( Jamieson et al, 1995 ; Ricketts et al, 1998 ; Lamadé et al, 2021 ), while the 11β-HSD2 performs the opposite role as the 11β-HSD1 ( Brown et al, 1993 ; McMullen et al, 2012 ; Chen et al, 2021 ).…”

“…Since then, many studies in humans and animal models support the hypothesis that poor nutrition in utero , maternal stress (e.g., depression, anxiety, fatigue, toxic exposure), exogenously administered hormones (e.g., synthetic glucocorticoid, sGC), and other factors could change fetal structure, function, and metabolism, leading to a long-last effects on offspring throughout the whole life. Moreover, metabolic syndrome such as cardiovascular disease in humans and offspring growth performance in livestock are the mostly reported consequences of those adverse factors ( Nathanielsz, 2006 ; Barker, 2007 ; Gicquel et al, 2008 ; Beauchamp et al, 2015 ; Sand et al, 2019 ; Davies et al, 2021 ). Therefore, understanding of the underpinning mechanisms of fetal programming could provide cues to develop intervention strategies for poor postnatal growth performance in domestic animals and adult chronic diseases in humans caused by maternal stresses ( Cox et al, 2012 ).…”