title: Effect of pyrimethamine treatment on male rat testicular cell population development.
abstract: Pyrimethamine (PYR) is a drug used in the treatment of newborn with congenital Toxoplasmosis. Even when PYR is highly specific against parasites, it may provoke neutropenia in the patients apart from other affectations, conditions that usually justify its suspension. Moreover, medication against congenital toxoplasmosis coincides with the proliferation stage of Sertoli and germ cells. Although, there are several reports on the effect of this drug on mature testes, records of its effects on the testes of young individuals yet in the process of growth are still lacking. This work was aimed to study the effects of in vivo administration of PYR in the first 21 days of life of male rat pups by evaluating their testicular alterations and its long-term sequels on fertility. Through the determination of the levels of seminiferous epithelium maturity, apoptotic index and cell proliferation index at 7, 14, 35 and 90 days post-natal using immunocytochemical studies. The fertility of the treated rats was evaluated at 90 days. PYR-treated animals were found to undergo some kind of delays in seminiferous epithelium maturity, decreased cell proliferation index and an increase in apoptosis when compared with the control (p < 0.05). Epididymal sperm counts were also affected (p < 0.05). The application of folic acid (FA) in newborns treated with PYR decreased the severity of the problem (p < 0.05). This study provides strong evidence that the effect of PYR on testicular development is specific. It reinforces the importance of FA application in neonates treated with PYR to prevent the effect of the later on spermatogenesis.
authors.affiliation: Subdirección de Medicina Experimental, Instituto Nacional de Pediatría, Mexico D.F., Mexico; Facultad de Medicina Veterinaria y Zootecnia, UNAM, Mexico D.F., Mexico.
authors.forename: O
authors.initials: O
authors.lastname: Gutiérrez-Pérez
authors.forename: C
authors.initials: C
authors.lastname: Durand-Montaño
authors.forename: J C
authors.initials: JC
authors.lastname: Rojas-Castañeda
authors.forename: M
authors.initials: M
authors.lastname: Chavez-Saldaña
authors.forename: R M
authors.initials: RM
authors.lastname: Vigueras-Villaseñor
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005298:Fertility / Q000187:drug effects*; D005492:Folic Acid / Q000494:pharmacology; D005493:Folic Acid Antagonists / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D011739:Pyrimethamine / Q000009:adverse effects* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012670:Seminiferous Epithelium / Q000187:drug effects*; D012708:Sertoli Cells / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000166:cytology / Q000473:pathology*; D014123:Toxoplasmosis / Q000188:drug therapy
chemical_list: D005493:Folic Acid Antagonists; D005492:Folic Acid; D011739:Pyrimethamine
keywords: Sertoli cells; cell proliferation; gonocytes; pyrimethamine; seminiferous epithelium; testis