Abstract
OBJECTIVESTo determine the role of the RBP4/PiC/SIRT3 signaling pathway in the opening of the mitochondria permeability transition pore (mPTP) in offspring rats with hypothyroidism during pregnancy.METHODSSixty Sprague-Dawley (SD) rats were employed in this study. Pregnancy was deemed successful when a sperm was found in the uterus. After one week of pregnancy, offspring rats were divided into the following groups: overall hypothyroidism group (OH group), subclinical hypothyroidism group (SCH group), and normal control group (CON group). The establishment of the hypothyroidism model was confirmed when the serum thyroid stimulating hormone (TSH) levels were higher than normal value and TT4 level was within the normal range. The renal mitochondria of offspring rats were extracted on the 14th postnatal day (P14) and 35th postnatal day (P35).RESULTSAt P14, no significant differences in the degree of mPTP opening and expression of phosphoric acid carrier vector (PiC) were detected between the rats in the OH group and the SCH group. However, the expression level of silent mating-type information regulation 3 homolog (SIRT3) was markedly reduced. Retinol-binding protein 4 (RBP4) expression increased in the rats from the OH group, relative to that in those from the SCH group. At P35, the degree of mPTP opening and the expression levels of PiC and RBP4 in the OH group were higher than those in the SCH group. However, SIRT3 expression in the OH group was lower than that observed in the SCH group.CONCLUSIONRBP4 plays an important role in early renal mitochondrial damage and renal impairment in rats suffering from hypothyroidism during pregnancy. The RBP4/PiC/SIRT3 pathway is thus involved in the opening of the renal mPTP in offspring rats with hyperthyroidism.
Highlights
Owing to improvements in the economy and the popularization of iodized salt, the prevalence rate of thyroid disease has reduced considerably in the recent past[1]
After one week of pregnancy, offspring rats were randomly divided into three groups: subclinical hypothyroidism group (SCH group), overall hypothyroidism group (OH group), and control group (CON group)
The levels of TT4 and thyroid stimulating hormone (TSH) were measured throughout pregnancy. offspring rats in each group were weighed on the 14th postnatal day (P14) and 35th postnatal day (P35), and the serum TT4 and TSH levels were measured
Summary
Owing to improvements in the economy and the popularization of iodized salt, the prevalence rate of thyroid disease has reduced considerably in the recent past[1]. Thyroid disease remains the second most prevalent endocrine disease in China [2]. No potential conflict of interest was reported. Received for publication on June 27, 2020. Accepted for publication on October 15, 2020
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