Anatomical and immunohistochemical analyses of the fusion of the premaxillary-maxillary suture in human fetuses.

Purpose: The development of the premaxillary-maxillary suture (PMS) in human fetuses and a possible association between the fusion time of the PMS and maxillary deficiency were investigated. Expression of transforming growth factor beta (TGF-β1 and TGF-β3) and of fibulins (fibulin‑1 and fibulin-5) were also investigated.

Methods: We analyzed 36 human fetus cadavers (19 males, 17 females; average age 23.97 ± 2.57 gestational weeks [gws], range 11-35 gws). Two cases, diagnosed with Down syndrome (DS), were characterized with maxillary deficiency; 34 fetus cadavers did not show any craniofacial abnormalities. The PMS was analyzed anatomically, followed by semi-quantitative immunohistochemical (IHC)-based expression analyses (i.e., TGF-β1/-β3, fibulin-1/-5). Spearman correlation test was conducted to investigate correlations.

Results: In the fetuses without DS, the labial region of the PMS was open at 11 gws, after which it began to ossify from the middle to the upper and lower ends of the suture, typically fusing completely at 27 gws. Fetuses with DS demonstrated complete fusion of the labial region of PMS with a spongy bone structure at 23 gws and those without DS at 27 gws. IHC revealed similar patterns of TGF-βs and fibulins expression in the PMS during the human fetal period. There were significant positive correlations between the expression of TGF-β1 and TGF-β3 (r = 0.64, p = 0.009), TGF-β1 and fibulin‑1 (r = 0.66, p = 0.008), and TGF-β3 and fibulin‑1 (r = 0.67, p = 0.006).

Conclusion: Premature fusion of the PMS in the labial region during the human fetal period may be associated with maxillary deficiency, which is related to a class III malocclusion. Overall, the similar expression patterns of TGF-β1, TGF-β3 and fibulin‑1 suggested a close relationship between these factors in regulating the development of the PMS.