Study On The Role And Mechanism Of Aquaproin-8 In Follicular Development And Blood Biomarkers In Mouse Model Of Alzheimer’s Disease

Part 1: Study on the role and mechanism of aquaproin-8 in follicular developmentAquaporin-8(AQP8)is a water channel protein expressed exclusively in granulosa cells(GCs)in mouse ovary.Our previous studies demonstrated that AQP8 participates in folliculogenesis such as formation of follicle,ovulation and atresia using AQP8-deficient(AQP8-/-)mice.However,its physiological function in formation of the antral follicle is still largely unknown.In the present study,we observed significantly increased numbers of antral follicle in AQP8-/-ovaries,and also significantly increased numbers of follicular antrum formation in vitro 3D culture of AQP8-/-follicles,compared to that of wild-type(WT).Functional detections of AQP8-/-GCs indicated that cell proliferation is impaired with treatment of FSH,and wound healing and transwell migration are also impaired without or with treatment of FSH,compared to that of WT.Whereas,the biosynthesis of estradiol and progesterone,as well as the mRNA levels of three key steroidogenic enzyme genes(CYP19A1,CYP11A1 and StAR)in AQP8-/-GCs did not alter,even with treatment of FSH or/and testosterone.Based on these evidences we proposed a novel theory underlying the follicular antrum formation that impaired proliferation and invasion of GCs induce the occurrence and coalescence of foci or gaps in preantral follicle,leading to accumulation of antrum.This study may offer new insight into the molecular mechanisms of folliculogenesis.Part 2: the research of blood biomarkers in mouse model of Alzheimer’s diseaseAs a progressive age-related neurodegenerative disorder,Alzheimer’s disease(AD)is a global health concern.Despite the availability of psychological testing,neuroimaging,genetic testing and biochemical assays of cerebrospinal fluid,convenient and accurate plasma biomarkers for prediction and diagnosis of AD are still lacking.The present study aims to longitudinally evaluate the feasibility of β-amyloid proteins,α-2macroglobulin(α-2M),Complement factor H(CFH)and clusterin as plasma biomarkers of AD.Using APP/PS1 transgenic and wild-type(WT)mice,cognitive impairment and amyloid plaque counts in the brain were evaluated over a range of ages by the Morris water maze test and immunohistochemistry methods,respectively.Serum Aβ40,Aβ42,α-2M,CFH and clusterin levels were measured by ELISA and correlated with AD progression.APP/PS1 transgenic mice presented progressive AD characteristics at ages of 3,6,9 and 12 months.Serum Aβ42 levels and Aβ42/Aβ40 ratios increased significantly in transgenic 3-and 6-month-old mice compared to controls.Serum CFH levels decreased significantly in 3-and 6-month-old transgenic mice compared to controls.Meanwhile,serum clusterin levels increased significantly in 12-month-old transgenic mice compared to controls.The α-2M level was not significantly different between transgenic and WT mice.The APP/PS1 transgenic mouse is a model of familial AD.The present study indicated that the serum Aβ42,Aβ42/Aβ40 ratio and CFH level are potential biomarkers in preclinical and early stages of AD,while serum clusterin is a potential biomarker in the late stage of AD.