Perinatal exposure to Bisphenol A disturbs the early differentiation of male germ cells |
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| Affiliation: | 1. Cell Biology Unit, Institut Pasteur de Montevideo, Mataojo 2020, CP 11400 Montevideo, Uruguay;2. Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquímica y Ciencias Biológicas, Ciudad Universitaria UNL, Ruta Nacional N°168, km 472, CPA S3000ZAA, Santa Fe, Argentina;3. Transgenic and Experimental Animal Unit, Institut Pasteur de Montevideo, Mataojo 2020, CP 11400 Montevideo, Uruguay;1. LR18ES36, University of Gabes, Faculty of Sciences of Gabes, Gabes, Tunisia;2. BIOLIVAL LR-14ES06, University of Monastir, Monastir, Tunisia;1. Department of Urology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, No 300 Guangzhou Road, Nanjing 210000, China;2. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China;1. Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children''s, Hospital, Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang, 325027, China;2. Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children''s Hospital of Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang, 325027, China;1. Instituto de Salud y Ambiente del Litoral (ISAL, UNL-CONICET), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral (UNL), Santa Fe, Argentina;2. Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany |
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| Abstract: | Understanding the effects of Bisphenol A (BPA) on early germ cell differentiation and their consequences in adult life is an area of growing interest in the field of endocrine disruption. Herein, we investigate whether perinatal exposure to BPA affects the differentiation of male germ cells in early life using a transgenic mouse expressing the GFP reporter protein under the Oct4 promoter. In this model, the expression of GFP reflects the expression of the Oct4 gene. This pluripotency gene is required to maintain the spermatogonial stem cells in an undifferentiated stage. Thus, GFP expression was used as a parameter to evaluate the effect of BPA on early germ cell development. Female pregnant transgenic mice were exposed to BPA by oral gavage, from embryonic day 5.5 to postnatal day 7 (PND7). The effects of BPA on male germ cell differentiation were evaluated at PND7, while sperm quality, testicular morphology, and protein expression of androgen receptor and proliferating cell nuclear antigen were studied at PND130.We found that perinatal/lactational exposure to BPA up-regulates the expression of Oct4-driven GFP in testicular cells at PND7. This finding suggests a higher proportion of undifferentiated spermatogonia in BPA-treated animals compared with non-exposed mice. Moreover, in adulthood, the number of spermatozoa per epididymis was reduced in those animals perinatally exposed to BPA.This work shows that developmental exposure to BPA disturbed the normal differentiation of male germ cells early in life, mainly by altering the expression of Oct4 and exerted long-lasting sequelae at the adult stage, affecting sperm count and testis. |
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| Keywords: | Oct4 BPA Germ cell Differentiation |
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