Nemolato Sonia, Messana Irene, Cabras Tiziana, Manconi Barbara, Inzitari Rosanna, Fanali Chiara, Vento Giovanni, Tirone Chiara, Romagnoli Costantino, Riva Alessandro, Fanni Daniela, Di Felice Eliana, Faa Gavino, Castagnola Massimo
Dipartimento di Citomorfologia, Università di Cagliari, Cagliari, Italy.
PLoS One. 2009;4(4):e5109. doi: 10.1371/journal.pone.0005109. Epub 2009 Apr 1.
Thymosin beta(4), its sulfoxide, and thymosin beta(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 beta-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 beta(4) concentration: more than 2.0 micromol/L versus 0.1 micromol/L). On the other hand, the ratio between thymosin beta(4) and thymosin beta(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 beta(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.
This study outlines for the first time that salivary glands during foetal life express and secrete peptides such as beta-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.
采用反相高效液相色谱-电喷雾离子阱质谱联用技术，在人类早产新生儿的全唾液中检测到了胸腺素β4、其亚砜以及胸腺素β10。
方法/主要发现：尽管个体间差异较大，但β-胸腺素的浓度随孕龄（孕龄：胎龄加出生后的实际年龄）呈反比趋势增加，在孕龄190天（27周）时达到的值比成人全唾液中的值高二十多倍（胸腺素β4浓度：大于2.0微摩尔/升，而成年人为0.1微摩尔/升）。另一方面，在整个检测的孕龄范围（孕龄190 - 550天）内，胸腺素β4与胸腺素β10的比值呈现出约为4的恒定值。为了研究胸腺素β4的来源，并更好地确定其作为胎龄函数的产生趋势，从胎龄84天（12周）开始，对不同早产胎儿的大唾液腺和小唾液腺进行了免疫组织化学分析。在所有腺体中均可见反应性颗粒，在胎龄约140 - 150天时表达量最高，尽管个体间和个体内差异较大。在婴儿和成人的腺泡细胞中未观察到反应性颗粒，仅在导管细胞中有弥漫性细胞质染色。
本研究首次概述了胎儿期唾液腺表达并分泌诸如β-胸腺素等可能参与口腔及其附属器发育的肽类。其分泌从胎龄约12周增加至约21周，随后减少，在预产期时几乎消失，此时腺体转向分泌成人特异性唾液肽。观察到的这种转变可能是胎儿发育过程中涉及其他外分泌腺和内分泌腺的进一步分泌转变的一个例子。
