Perinatal exposure to Bisphenol A disturbs the early differentiation of male germ cells

• Published in: Reproductive toxicology (Elmsford, N.Y.) Vol. 98; pp. 117 - 124
• Main Authors: Pagotto, Romina, Santamaría, Clarisa G., Harreguy, María Belén, Abud, Julián, Zenclussen, María Laura, Kass, Laura, Crispo, Martina, Muñoz-de-Toro, Mónica M., Rodriguez, Horacio A., Bollati-Fogolín, Mariela
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-12-2020; Elsevier
• Subjects: Animals; Benzhydryl Compounds; BPA; Cell Differentiation; Cell Proliferation; Differentiation; Endocrine Disruptors; Female; Germ cell; Germ Cells; Life Sciences; Male; Maternal-Fetal Exchange; Mice, Transgenic; Oct4; Octamer Transcription Factor-3; Phenols; Pregnancy; Prenatal Exposure Delayed Effects; Receptors, Androgen; SOXB1 Transcription Factors; Sperm Count; Sperm Motility; Testis; Germ cell; Oct4; BPA; Differentiation
• ISSN: 0890-6238; 1873-1708
• DOI: 10.1016/j.reprotox.2020.09.004

•BPA conditions the early differentiation of male germ cells.•Perinatal exposure to BPA favors the undifferentiated state of spermatogonial population.•Sperm count in the adult can be altered by early life exposure to BPA.
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.