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

PAGOTTO, ROMINA; SANTAMARÍA, CLARISA G.; BELÉN, HARREGUY MARÍA; ABUD, JULIÁN; ZENCLUSSEN, MARÍA LAURA; KASS, LAURA; CRISPO, MARTINA; MUÑOZ-DE-TORO, MÓNICA M.; RODRIGUEZ, HORACIO A.; BOLLATI-FOGOLÍN, MARIELA

REPRODUCTIVE TOXICOLOGY (ELMSFORD, N.Y.)

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2020

0890-6238

Understanding the effects of Bisphenol A (BPA) on early germ cell differentiation andtheir consequences in adult life is an area of growing interest in the field of endocrinedisruption. Herein, we investigate whether perinatal exposure to BPA affects theJournal Pre-proofdifferentiation of male germ cells in early life using a transgenic mouse expressing theGFP reporter protein under the Oct4 promoter. In this model, the expression of GFPreflects the expression of the Oct4 gene. This pluripotency gene is required to maintainthe spermatogonial stem cells in an undifferentiated stage. Thus, GFP expression wasused 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, fromembryonic day 5.5 to postnatal day 7 (PND7). The effects of BPA on male germ celldifferentiation were evaluated at PND7, while sperm quality, testicular morphology, andprotein expression of androgen receptor and PCNA were studied at PND130.We found that perinatal/lactational exposure to BPA up-regulates the expression ofOct4-driven GFP in testicular cells at PND7. This finding suggests a higher proportionof undifferentiated spermatogonia in BPA-treated animals compared with non-exposedmice. Moreover, in adulthood, the number of spermatozoa per epididymis was reducedin those animals perinatally exposed to BPA.This work shows that developmental exposure to BPA disturbed the normaldifferentiation of male germ cells early in life, mainly by altering the expression of Oct4and exerted long-lasting sequelae at the adult stage, affecting sperm count and testis.