Role of thyroid hormones on Sertoli cell proliferation and differentiation and on sperm production of progeny from carbamazepine treated-rats during the pregnancy and lactation

• Grant number: 12/05905-9
• Support Opportunities: Regular Research Grants
• Duration: January 01, 2013 - March 31, 2015
• Field of knowledge: Biological Sciences - Morphology - Embryology
• Principal Investigator: Sandra Maria Miraglia Valdeolivas
• Grantee: Sandra Maria Miraglia Valdeolivas
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Samara Urban de Oliva ; Taiza Stumpp Teixeira

Abstract

Carbamazepine (CBZ) is a widely utilized drug in the control of seizure and affective disturbs as well as in the treatment of trigeminal neuralgia. It presents inhibitory effect of the testicular steroidogenesis and can cause alterations of bioactive testosterone plasmatic levels. Thus, mechanisms that depend on the adequate level of testicular testosterone can be altered by the administration of this drug even after birth. In this case, the development and maintenance of spermatogenesis in the post-natal phase are directly or indirectly dependent on the testosterone plasmatic level. Therefore, functional alterations of Leydig cells during the intrauterine phase can provoke testicular damage as well as injury of genital ducts and accessory glands; these modifications will probably be noted only postnataly, i.e., in the puberty and adulthood. CBZ is also teratogenic and causes congenital malformations of the urogenital apparatus; besides, it provokes hypothyroidism in patients that have chronically taken it. Regarding this subject, the role of the thyroid hormones (T3 and T4) on the control of the proliferation and differentiation of Sertoli cells must be considered, both in pre-natal and post-natal phases, since these cells exert a fundamental function on the establishment and homeostasis of the seminiferous epithelium microenvironment. Sertoli cells also control the differentiation and proliferation of germ cells. Moreover, during the embryonic phase, the interaction between Sertoli cells and gonocytes is crucial and has an important influence upon the normal development of male gonad, in both pubertal and adult phases. Considering the aforementioned fact, there is also the clinical aspect, since CBZ is uninterruptedly utilized by fertile women that need it. Data related to the possible side effects of CBZ exposition during pregnancy to male offspring reproduction are scarce and fragmented; in addition, in the literature consulted, there are very few studies about this subject. For that reason and because the clinical protocols including the continuous use of CBZ by pregnant patients or by women with potential reproductive capacity, we decided to carry out this experimental study with the aim to clarify the late effects of CBZ on spermatogenesis and sexual maturity of the offspring from rats treated during pregnancy. Previous study performed by our group showed that carbamazepine provokes late reproductive alterations in rats from the weaning (23 days) until the puberty and adult phase. Thus, in view of the continued use of CBZ in clinic for treatment of childberring age women, it was decided to carry out this study to contribute to the clarification of the late effects of CBA on spermatogenesis and male sexual maturation of male offsprinf from mothes treated during pregnancy and lactation. We intend to perfom: 1- thyroid hormones levels (T3 and T4) as a result of chronic CBZ administration, and the possible occurrence of hypothyroidism in the mother and pups; 2- the primary implication of thyroid hormones alteration on proliferation and differentiation of Sertoli cells, and 3- therefore, the secondary effects in spermatogenesis on rats in neonatal, prepuberty, peripuberty, puberty and adulthood phases from treated-mothers throughout gestation and lactation period. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ANDRETTA, RHAYZA ROBERTA; OKADA, FATIMA KAZUE; PACCOLA, CAMILA CICCONI; STUMPP, TAIZA; DE OLIVA, SAMARA URBAN; MIRAGLIA, SANDRA M.. Carbamazepine-exposure during gestation and lactation affects pubertal onset and spermatic parameters in male pubertal offspring. REPRODUCTIVE TOXICOLOGY, v. 44, p. 52-62, APR 2014. (12/05905-9)

OLIVA, SAMARA U.; ANDRETTA, RHAIZA R.; SIMAS, JOANA N.; TESSER, RENATO B.; PACCOLA, CAMILA C.; MIRAGLIA, SANDRA M.. Thyroid hormones, Sertoli cell proliferation and differentiation in progenies from carbamazepine-treated rat dams during pregnancy and lactation. ANDROLOGIA, v. 53, n. 3, JAN 2021. (12/05905-9)