Thymosin β(4) and β(10) Levels in Pre-Term Newborn Oral Cavity and Foetal Salivary Glands Evidence a Switch of Secretion during Foetal Development

BACKGROUND: Thymosin β(4), its sulfoxide, and thymosin β(10) were detected in whole saliva of human pre-term newborns by reversed-phase high performance chromatography coupled to electrospray ion-trap mass spectrometry. METHODOLOGY/PRINCIPAL FINDINGS: Despite high inter-individual variability, concentration of β-thymosins increases with an inversely proportional trend to postmenstrual age (PMA: gestational age plus chronological age after birth) reaching a value more than twenty times higher than in adult whole saliva at 190 days (27 weeks) of PMA (thymosin β(4) concentration: more than 2.0 µmol/L versus 0.1 µmol/L). On the other hand, the ratio between thymosin β(4) and thymosin β(10) exhibits a constant value of about 4 along all the range of PMA (190–550 days of PMA) examined. In order to investigate thymosin β(4) origin and to better establish the trend of its production as a function of gestational age (GA), immunohistochemical analysis of major and minor salivary glands of different pre-term fetuses were carried out, starting from 84 days (12 weeks) of gestational age. Reactive granules were seen in all glands with a maximum of expression around 140–150 days of GA, even though with high inter- and intra-individual variability. In infants and adults reactive granules in acinar cells were not observed, but just a diffuse cytoplasmatic staining in ductal cells. SIGNIFICANCE: This study outlines for the first time that salivary glands during foetal life express and secrete peptides such as β-thymosins probably involved in the development of the oral cavity and its annexes. The secretion increases from about 12 weeks till to about 21 weeks of GA, subsequently it decreases, almost disappearing in the period of expected date of delivery, when the gland switches towards the secretion of adult specific salivary peptides. The switch observed may be an example of further secretion switches involving other exocrine and endocrine glands during foetal development.