Lung development in human occurs in sixstages; embryonic, pseudoglandular, canalicular, saccular, alveolar and microvascular maturation,while in rats, it occurs only in five stages;embryonic, pseudoglandular, canalicularsaccular, and alveolar. Lung development begins in the intrauterine life andcompletes its maturation postnatally.
Maternal diabetes may interfere with the development of almost every organ in the fetus including the lungs. Newborn children of diabetic mothers may have an increased morbidity and mortality because of RDS (respiratory distress syndrome).The latter is due to a deficient production of pulmonary surfactant caused by an immature lung. Cortisol has a role in lung maturation since it stimulates surfactant production by the pneumocyte type II cells.
This study was aimed to assessthe effects ofmaternal hyperglycemiainduced by streptozatocin on the prenatal and postnatal lung developmentin
rat and the possibleeffect ofpostnatal hydrocortisone administration on thelung alveoli of rat offspring.
Thirty three adult pregnantfemale albino rats were used in this study.The pregnant rats were divided into two main groups; prenatal group and postnatal groups.
A-Prenatal group:
This group consisted of twelve pregnant rats which was subdivided intoprenatal control and prenatal diabeticsubgroups.
1-Prenatalcontrolsubgroup at the 18th day of gestation: it included the fetuses of three pregnant healthy female rats at the 18th gestational day.
2-Prenatalcontrolsubgroup at the 20th day of gestation:it included the fetuses ofthree pregnant healthy female rats at the 20th gestational day.
3-Prenataldiabeticsubgroup at the 18th day of gestation:it included the fetuses of three pregnant diabetic female rats at the 18th gestational age.
4-Prenataldiabeticsubgroup at the 20th day of gestation:it included the fetuses of three pregnant diabetic female rats at the 20th gestational day.
B-Postnatal group:
This group consisted of twenty one pregnant tats which was subdivided into postnatal control and postnatal experimental groups.
1-Postnatalcontrolsubgroupatthe day of birth:It included theoffspring of three pregnant healthy female rats at the day of birth.
2- Postnatalcontrolsubgroupat the 7th day after birth:It included theoffspring of three pregnant healthy female rats at the7th day after birth.
3-Postnatalcontrolsubgroupat the14th day after birth: It included theoffspring of three pregnant healthy female rats at the14th day after birth.
4-Postnataldiabeticsubgroupatthe day of birth:It included theoffspring of three pregnant diabetic female at the day of birth.
5- Postnataldiabeticsubgroupatthe7th day after birth:It included theoffspring of three pregnant diabetic female rats at the7th day after birth.
6- Postnataldiabeticsubgroupat the14th day after birth:It included theoffspring of three pregnant diabetic female rats at the 14th day after birth.
7-Cortisone treated subgroup:This subgroup included the offspring of three pregnant diabetic female rats, which had been injected intraperitoneally with hydrocortisone as follows:
These offspring had been injected by hydrocortisone just after birth in single dose of 2mg/kg body weight.Some of these offspring were anaethesizedand decapitated two hours after the injection and their lungs were extracted for study.
The rest the offspringhad been received hydrocortisone injectionfrom the second day of birthtill the sixth day after birth. in a tapering dose such as 2mg/kg body weight on the second day after birth, then 1mg/kg on the third &fourth day after birth, then 0.5mg/kg/day at fifth &sixth day after birth. These offspring were anaethesized and decapitated at two different ages(the7th day after birth and the14th day after birth). The lungs were extracted and prepared for light and electron microscopic analysis.
In the presentstudy,the different stages of the lung development appeared in the different control subgroups as follows: the fetal rat lungs at the 18th day of gestation were in the late pseudoglandular stage where some air spaceswere rounded while others were wavy tubules and were separated by a highly cellular mesenchyme.However the fetal rat lungs at the 20th day of gestation were in the late canalicular stage where all airway generations became greatly widened and elongated resulting in a marked reduction in the pulmonary interstitial cells with an increased capillary number. At the day of birth, the neonatal rat lung appeared in the saccular stage of developmentwith the terminal portions of the acinar canals formed of widened airspaces termed air saccules. At the7th day after birth, the neonatal rat lungs were in the early alveolar stage of development with the appearance of secondarysepta.These septa along with the primary septa had subdivided the air saccules into smaller units; primitive alveoli.At 14thday after birth, theneonatal rat lung was formed of alveoli with thin interalveolar septa containing only one layer of blood capillary and the epithelial lining of the alveoli became differentiated into type I and type II alveolar cells.
On the other hand, the fetal rat lung of diabetic mothers in this study showed a delay in lung development and a delay in the differentiation of the typeII pneumocytes. This was evidenced in the different diabetic pre-and postnatal subgroups as follows.At the 18th day of gestation, the fetal lungs of the diabetic motherswere in the embryonic stage,with the bronchial buds lined by a thick layer of stratified squamousepithelium,while at the 20th day of gestation, the fetal rat lungswere in the early pseudoglandular stagesince their lungsshowed a progressive branching of the bronchial buds to primitive bronchioles in a cellular mesenchymal tissue.Also,the offspring lungs werestill in the canalicular stage even atthe day of birth and were remained in this stage till the 7th day after birth .At 14th dayafter birth, the offspring lungs of the diabetic mothers appeared in the saccular phase, with thickened inter-saccular septum and narrow saccular space
Hydrocortisone enhanced lung maturity and enhanced excessive branching and thinning of the intersaccular septa and this appeared in this present work in the cortisone-treated subgroup. This finding had indicated an increasein the maturity of thepneumocyte type II cellsand increased surfactant secretion.
Conclusion:
Development of the lung occurs in stages,and these stages begin in the intrauterine life and are completed postnatally. Uncontrolled D.M. delays lung development, so, diabetic mothers have to control their glycemic level in the blood especiallyduring the period of gestation. Neonates of mothers with uncontrolled D.M., suffering from RDS should be given hydrocortisone to enhance lung maturity
Recommendation:
We recommend further studies concerning other drugs that mayenhance lung maturitysuch as exogenous surfactant which may enhance maturity more rapid than cortisone.
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