Experimental studies of the di-n-butyl phthalate and mono-(2-ethylhexyl) phthalate effect on testicular development in rodents

Author(s)

Caroline Maria Christante

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2017-05-31

Examining board members

Rejane Maira Góes; João Ernesto de Carvalho; Adriana Souza Torsoni; Carla Dal Bianco Fernandez; Taiza Stumpp Teixeira

• Advisor: Rejane Maira Góes

Abstract

Phthalate esters such as di-n-butyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP) and its active metabolite, mono-(2-ethylhexyl) phthalate (MEHP), may exert adverse effects on reproductive hormones and on fetal/neonatal germ cells in a species-specific manner. On the other hand, the docosahexaenoic acid (DHA - 22:6 n-3), a long-chain polyunsaturated fatty acid (PUFA) abundantly found in oily fish sources, seems to be beneficial for testosterone production, spermatogenesis and sperm motility. It is also known that MEHP and DHA act on the same metabolic pathways involved in cholesterol/lipid synthesis but in antagonistic ways. Thus, the present study evaluated whether the maternal exposure to DBP interferes with the development of the Mongolian gerbil testis during the first six weeks of postnatal development. It evaluated the action of DHA alone or in combination with MEHP on the mouse fetal testis as well, using the organotypic culture. For this, testis of male gerbils born from control (C) or exposed pregnant mothers to mineral oil (O) or DBP (100 mg/kg from 8 to 23 days post conception) were checked at the ages of 1, 7, 14, 28, 35 and 42 days. It was also conducted in vitro analysis of mice testes at 13.5 days post-conception (dpc) cultured in medium only (controls), DHA (50µM), MEHP (20µM) or both (50µM DHA/20µM MEHP) for 24 or 72 hours. As demonstrated by our results, DBP impaired the density of mitotic figures at birth and the total number of gonocytes (NG) at 7 postnatal days, besides increasing steroidogenic activity at the end of the first week of life, in the gerbil. The mineral oil, on the other hand, decreased testosterone and raised estrogen plasmatic levels at 7 and 28 days, respectively. In vitro analisys indicated that MEHP did not change the NG. Nevertheless, DHA stimulated testosterone secretion after 72h. This lipid also induced a marked extravasation of gonocytes into the interstitial tissue, a pro-apoptotic effect of cell populations in the stroma of the gonad and morphological alterations in the testicular cords after 3 days of culture. In conclusion, the present indications provided by in vivo experiments demonstrated that the first week of the gerbil postnatal life is more sensitive to deleterious effects of phthalate on the number of germ cells and steroidogenesis. In vitro experiments, therefore, indicated that the testicular development, for the mouse, was impaired by expose to DHA, which induced degenerative alterations in the Sertoli cells, worsened when combined with MEHP (AU)

• FAPESP's process: 13/19591-9 - Experimental studies of the di-n-butyl phthalate and mono-(2-ethylhexyl) phthalate effect on testicular development in rodents
• Grantee: Caroline Maria Christante
• Support Opportunities: Scholarships in Brazil - Doctorate