Developmental Timing Determines the Protective Effect of Maternal Electroacupuncture on Perinatal Nicotine Exposure-Induced Offspring Lung Phenotype

Abstract

Introduction. Environmental exposure of the developing offspring to cigarette smoke or nicotine is an important predisposing factor for many chronic respiratory conditions, such as asthma, emphysema, pulmonary fibrosis, and so forth, in the exposed offspring. Studies showed that electroacupuncture (EA) applied to maternal “Zusanli” (ST36) acupoints during pregnancy and lactation protects against perinatal nicotine exposure- (PNE-) induced lung damage. However, the most effective time period, that is, prenatal vs. postnatal, to attain this effect has not been determined. Objective. To determine the most effective developmental timing of EA’s protective effect against PNE-induced lung phenotype in the exposed offspring. Methods. Pregnant rats were given (1) saline (“S” group); (2) nicotine (“N” group); (3) nicotine + EA, exclusively prenatally (“Pre-EA” group); (4) nicotine + EA, exclusively postnatally (“Post-EA,” group); and (5) nicotine + EA, administered both prenatally and postnatally (“Pre- and Post-EA” group). Nicotine was injected once daily (1 mg/kg, 100 μl) and EA was administered to bilateral ST36 acupoints once daily during the specified time-periods. At the end of the experimental periods, key hypothalamic pituitary adrenal (HPA) axis markers in pups and dams, and lung function, morphometry, and the central molecular markers of lung development in the offspring were determined. Results. After nicotine exposure, alveolar mean linear intercept (MLI) increased, but mean alveolar number (MAN) decreased and lung PPARγ level decreased, but glucocorticoid receptor (GR) and serum corticosterone (Cort) levels increased, in line with the known PNE-induced lung phenotype. In the nicotine exposed group, maternal hypothalamic corticotropin releasing hormone (CRH) level decreased, but pituitary adrenocorticotropic hormone (ACTH) and serum Cort levels increased. In the “Pre- and Post-EA” groups, PNE-induced alterations in lung morphometry, lung development markers, and HPA axis were blocked. In the “Pre-EA” group, PNE-induced changes in lung morphometry, GR, and maternal HPA axis improved; lung PPARγ and serum Cort levels were slightly but not significantly improved. In contrast, the exclusive “Post-EA” group showed none of these benefits. Conclusions. Maternal EA applied to ST36 acupoints during both pre- and postnatal periods preserves offspring lung structure and function despite perinatal exposure to nicotine. EA applied during the “prenatal period” affords only limited benefits, whereas EA applied during the “postnatal period” is ineffective, suggesting that the EA’s effects in modulating PNE-induced lung phenotype are limited to specific time-periods during lung development.

Effect of electro‐acupuncture at ST 36 on maternal food restriction‐induced lung phenotype in rat offspring

“…In addition to improving general well‐being, it is known to exert beneficial effects on diseases of the digestive, 30 motor, 31 and immune systems 32 . And via its impact on the HPA axis, it exerts a protective effect on the respiratory system 22–25 …”

“…In line with the description in "Experimental Acupuncture Science," acupuncture site ST 36 was selected posterolateral to the knee joint about 5 mm from the fibular head. As described previously, [22][23][24][25] the acupuncture needles (0.20 mm × 13 mm, Catalog#: 1552484411, Hwato) were perpendicularly pierced into ST 36 bilaterally with a depth of 7 mm, connecting the negative pole of EA, and horizontally pierced into the skin 2 mm below ST 36, connecting the positive pole of EA. The EA parameters were as follows: frequency 2/15 Hz, intensity 1 mA, duration 20 min, and administered once a day between 10 a.m. and noon.…”

“…It is one of the most frequently used acupoints. It is easily reproducible and, in addition to its effects on the digestive system, it is effective in multiple other system diseases, including the respiratory system 22–25 . We have previously demonstrated that EA applied to maternal ST 36 blocks alterations in key lung developmental signaling pathways and the resulting offspring lung phenotype following perinatal nicotine exposure 22–25 .…”

“…It is easily reproducible and, in addition to its effects on the digestive system, it is effective in multiple other system diseases, including the respiratory system. [22][23][24][25] We have previously demonstrated that EA applied to maternal ST 36 blocks alterations in key lung developmental signaling pathways and the resulting offspring lung phenotype following perinatal nicotine exposure. [22][23][24][25] However, it is unknown whether it can also block the MFR-induced changes in lung developmental signaling pathways and the resultant lung phenotype.…”

The role of RNA m6A methylation in the regulation of postnatal hypoxia-induced pulmonary hypertension

“…The mean alveolar number (MAN) was Na/A (pieces/cm 2 ). MAN reflects alveolar density [ 27 ]. Microphotographs of IHC-stained sections were taken under a 200 × microscope and 400 × microscope.…”