Exposure To Benzo(a)pyrene Impairs The Corpus Luteum Vascular Network In Rats During Early Pregnancy

Objective: Benzo[a]pyrene(BaP)is a widespread environmental pollutant.Studies have reported that BaP exposure impair embryo implantation,however the underlying mechanism is unclear.The success of embryo implantation is closely related to luteal function.The corpus luteum(CL),the main source of progesterone during early pregnancy,plays a pivotal role in embryo implantation and pregnancy maintenance.The development of luteal vessel is very important for the luteal structure and function.Clinically,inappropriate luteal function may result in infertility or habitual abortion.Therefore,this study aimed to investigate the effects of BaP on the structure and function of CL and luteal vascularization during early pregnancy.Methods:1.Animals and treatment: From the first day of pregnancy,the treatment group was given 0.2 mg/kg body weight BaP by gastric administration,and the control group was administered corn oil.The rats were killed on D4,D7 and D9 of pregnancy,the uterus and ovaries were collected.2.The levels of estrogen and progesterone in serum were measured by Enzyme-linked immunosorbent assay(ELISA).3.HE and IF were applied to observe the morphology of corpus luteum and the construction of luteal vascular network,respectively.4.IHC,IF,Western-blot and Real-time PCR were used to detect the expression of related factors involved in luteal angiogenesis and maintenance.Results:1.Exposure to BaP reduced the number of implantation sites and the levels of estrogen and progesterone in serum.2.Exposure to BaP significantly decreased the number of corpus luteum and destroyed the luteal structure.3.BaP impacted the construction of the luteal vascular network,and the expression of CD31,SMA,and Collagen IV were markedly decreased in the BaP-treatment groups.4.The expression of VEGFR2,Ang-1,Ang-2,Tie2 and THBS1 were altered after BaP treatment.5.The expression of Notch1,Dll4 and Jag1 were affected by BaP exposure.6.BaP down-regulates the expression of Hey2,a target gene downstream of Notch signal in corpus luteum.Conclusion:Taken together,our results revealed that BaP can lessen the number of corpus luteum,influence the expression of related factors involved in luteal angiogenesis and maintenance regulation.BaP affected the regulation of Notch signaling pathway on luteal vascular development,impaired the construction of luteal vascular network and disturbed the luteal endocrine function,lead to adverse pregnancy outcomes.