Sulfasalazine exposure during pregnancy and lactation: reproductive outcomes in male rat offspring.

CONTEXT: Sulfasalazine (SAS) is a drug prescribed for pregnant and breastfeeding women with chronic inflammatory bowel diseases. SAS treatment induces transitory infertility in both adult men and male rats. Although SAS crosses the placenta and passes into maternal milk, the consequences of maternal SAS exposure on the reproductive development of male offspring needs further study. AIMS: The current study evaluated whether maternal SAS exposure interferes with the reproductive development of male rat offspring in the neonatal, infant, pubertal and adulthood periods. METHODS: Pregnant Wistar rats (n =10/group) received 300mg/kg/day of SAS dissolved in carboxymethyl cellulose (CMC), by gavage, from gestational day 0 to lactation day 21, and 3mg/kg/day of folic acid during gestation. The control group received CMC. KEY RESULTS: During puberty, maternal SAS exposure increased the total length of seminiferous tubules, and round cells were observed in the lumen of caput and cauda epididymis. Moreover, SAS induced oxidative stress-related alterations in the testes of infant and adolescent rats. CONCLUSIONS: Although maternal SAS treatment caused reproductive alterations in infant and adolescent male rats, in adulthood, there were no impairments in sperm parameters that could compromise fertility. IMPLICATIONS: This study investigated the consequences of maternal exposure to SAS on the reproductive development of male rat offspring from birth to adulthood, employing a human-relevant dose. Thus, this study provides information for better understanding of SAS treatment during critical periods of development.

Can resveratrol attenuate testicular damage in neonatal and adult rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin during gestation?

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is considered one of the most toxic dioxins. The effects of TCDD are exerted via binding to the aryl hydrocarbon receptor (AhR). The aim of the present study was to evaluate the possible protective effects of resveratrol, an AhR antagonist, against testicular damage caused by TCDD exposure during pregnancy. Pregnant female Sprague-Dawley rats were divided into four groups: a control group; a group treated with 1µgkg-1, p.o., TCDD on Gestational Day (GD) 15; a group treated with 20µgkg-1, p.o., resveratrol on GD10-21; and a group treated with both TCDD and resveratrol. Rats were weighed and killed, and neonatal testes were collected for histopathological analysis on Postnatal Day (PND) 1. At PND90, adult male rats were killed and the testes collected for histopathological analysis and determination of sperm count. Resveratrol had a protective effect against the effects of TCDD on Sertoli cell number in adult and neonate testes, as well as against the effects of TCDD on abnormal seminiferous tubules in adults. Combined administration of TCDD and resveratrol altered the kinetics of spermatogenesis and the proportion of neonatal testicular compartments compared with the control group In addition, combined TCDD and resveratrol treatment decreased seminiferous tubule diameter in adult male rats compared with the control group. In conclusion, resveratrol may protect against some TCDD-induced testicular damage, but, based on the parameters assessed, the administration of resveratrol and TCDD in combination may result in more severe toxicity than administration of either drug alone.

A High Fat Diet during Adolescence in Male Rats Negatively Programs Reproductive and Metabolic Function Which Is Partially Ameliorated by Exercise.

An interaction between obesity, impaired glucose metabolism and sperm function in adults has been observed but it is not known whether exposure to a diet high in fat during the peri-pubertal period can have longstanding programmed effects on reproductive function and gonadal structure. This study examined metabolic and reproductive function in obese rats programmed by exposure to a high fat (HF) diet during adolescence. The effect of physical training (Ex) in ameliorating this phenotype was also assessed. Thirty-day-old male Wistar rats were fed a HF diet (35% lard w/w) for 30 days then subsequently fed a normal fat diet (NF) for a 40-day recovery period. Control animals were fed a NF diet throughout life. At 70 days of life, animals started a low frequency moderate exercise training that lasted 30 days. Control animals remained sedentary (Se). At 100 days of life, biometric, metabolic and reproductive parameters were evaluated. Animals exposed to HF diet showed greater body weight, glucose intolerance, increased fat tissue deposition, reduced VO2max and reduced energy expenditure. Consumption of the HF diet led to an increase in the number of abnormal seminiferous tubule and a reduction in seminiferous epithelium height and seminiferous tubular diameter, which was reversed by moderate exercise. Compared with the NF-Se group, a high fat diet decreased the number of seminiferous tubules in stages VII-VIII and the NF-Ex group showed an increase in stages XI-XIII. HF-Se and NF-Ex animals showed a decreased number of spermatozoa in the cauda epididymis compared with animals from the NF-Se group. Animals exposed to both treatments (HF and Ex) were similar to all the other groups, thus these alterations induced by HF or Ex alone were partially prevented. Physical training reduced fat pad deposition and restored altered reproductive parameters. HF diet consumption during the peri-pubertal period induces long-term changes on metabolism and the reproductive system, but moderate and low frequency physical training is able to recover adipose tissue deposition and reproductive system alterations induced by high fat diet. This study highlights the importance of a balanced diet and continued physical activity during adolescence, with regard to metabolic and reproductive health.