Prevention of preterm birth (PTB) by inhibition of fkbp51
a technology of fkbp51 and preterm birth, which is applied in the direction of sexual disorder, biochemistry apparatus and processes, drug compositions, etc., can solve the problems of reducing affecting the survival rate reducing the number of infants born prematurely, so as to improve the activity of fkbp51 and enhance the activity of pr
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example 1
[0046]This example demonstrates the expression pattern of FKBP51 in mice and the effects of FKBP51 regulation on preterm birth (PTB) in mice.
[0047]FKBP51-knockout (KO; FKBP51− / −) and wild type (WT) animals mice (provided by Chad Dickey, PhD; USF Health Morsani College of Medicine) were used to analyze FKBP51 expression and test the hypothesis that FKBP51 regulates preterm birth in mice. To define the role of FKBP51 on birth timing, the gestational length was compared in pregnancies from WT or FKBP51 KO mice mated with WT male littermates (see FIG. 2). This analysis revealed significantly prolonged gestation (more than one day) in KO female mice compared to WT female mice, as shown in FIG. 3, providing the first evidence that FKBP51 regulates gestational length. Moreover, compared to the gestational length in non-stress WT controls, restrained stress significantly reduced gestational length in the stressed WT group (19.10 day vs. 18.72, P=0.018), as shown in FIG. 4, suggesting that g...
example 2
[0052]This example describes experiments comparing corticosterone levels in stressed vs. non-stressed mice.
[0053]In rodents, plasma corticosterone is considered to be the main glucocorticoid involved in regulating stress responses, and the presence of plasma cortisol in serum also has been confirmed in rodents (Gong et al., PLoS One, 10: e0117503 (2015)). The dynamics of mouse serum cortisol and corticosterone may be closely correlated under different physiological or stress conditions, and corticosterone may be a better adaptation-related biomarker than cortisol during chronic stress, whereas cortisol may be a quicker responder than corticosterone during severe acute stress. Therefore, serum corticosterone levels were analyzed in samples obtained from mice tested in Example 1. Blood sampling was performed at 10 to 11 am on gestation days (GDs) 11 after the first stress exposure in WT and KO mice and in non-stressed (control) groups. A commercially available enzyme-linked immunosorb...
example 3
[0054]This example demonstrates the effect of maternal and fetal genotype in stress-induced preterm birth (PTB).
[0055]To investigate the effect of fetal genotype in addition to maternal genotype on stressed reduced gestation length, additional experiments were performed using FKBP51 knockout (KO) female mice mated with FKBP51 KO male mice, which resulted in complete (fetal and maternal) absence of FKBP51 expression during pregnancy. In these experiments, which are illustrated in FIG. 16, female mice were mated with male mice for only 4 hours. The presence of sperm in vaginal smear or vaginal plug was accepted as gestation day (GD) 0. Time-mated pregnant WT and KO mice were randomly assigned to either a stress or control group. Restrained stress was initiated on GD8 and continued until GD18. Time-mated WT and KO pregnant females were monitored between GD18-22, and delivery was checked at 4 hour intervals. The appearance of the first pup was considered the parturition time, and the nu...
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