Effects of different stages, dosages and courses of prenatal dexamethasone exposure on testicular development in mice

Purpose

Observe the effects of prenatal dexamethasone exposure (PDE) at different stages, dosages, and courses on testicular morphology and multicellular function in offspring mice.

Methods

Pregnant Kunming mice were subjected to subcutaneous injections of dexamethasone at different stages [GD (gestational day) 14–15 and 16–17], dosages (0.2, 0.4, and 0.8 mg/kg·d), and courses (GD 14–15 and 14–17). Pregnant mice were euthanized on GD 18, and fetal serum and testicular samples were collected to assess serum testosterone level, testicular morphology, cellular proliferation/apoptosis function, expression of multicellular marker/functional gene, and the expression of developmental regulatory signalling pathways such as Notch and Wnt.

Results

PDE could lead to widening of the interstitial area and reduction of seminiferous tubules in fetal testicular tissue, accompanied by significant impairment of Sertoli cell function, particularly evident during late gestation, at high doses, and with multiple courses. However, changes in Leydig cells and spermatogonia function of PDE are not significant. Furthermore, we discovered that PDE could activate the Notch signalling pathway in Sertoli cells while inhibiting the Wnt signalling pathway.

Conclusion

PDE could affect fetal testicular development, especially for Sertoli cells during late gestation, at high doses and multiple courses. This study confirms the effects of PDE on testicular tissue morphology and multicellular function, providing a comprehensive understanding of the testicular developmental toxicity of dexamethasone and evidence for guiding rational medication during pregnancy.