Impaired follicular development and endocrine disorders in female rats by prepubertal exposure to toxic doses of cadmium

Abstract

Cadmium (Cd) has been associated with several physiological problems including reproductive and endocrine system dysfunction resulting in temporary infertility. The principal objective of this project was to investigate the effects of prepubertal exposure to toxic doses of Cd on puberty onset, the endocrine system, and follicular development. For this purpose, 16 female Sprague-Dawley rats weaned on postnatal day (PND) 21 were randomly divided into 4 groups ( n = 4 per group). The treatments were as follows: 0, 25, 50, and 75 mg/kg/day of cadmium chloride (CdCl2) by oral gavage from PND 21 to observation of first vaginal opening (VO). The results demonstrated that prepubertal exposure to different doses of CdCl2 delays the age of VO, first diestrus, and first proestrus via altering the concentrations of estradiol and progesterone. The low level of these steroid hormones contributed to lower differentiation and maturation of follicles and it finally led to reduced ovarian reservoir of follicles and impaired follicular development. The number of atretic follicles and secondary follicles with premature cavity increased in rats that received a high dose of CdCl2, whereas the number of secondary follicles and corpora luteum decreased in the same circumstances. Taken together, these data suggest that prepubertal exposure to toxic doses of Cd delays the onset of puberty via disorderliness in the concentration of steroid hormones and reduces the ovarian reservoir of follicles, as well as folliculogenesis.

Association between heavy metals exposure and infertility among American women aged 20–44 years: A cross-sectional analysis from 2013 to 2018 NHANES data

“…Excessive exposure to Cd, Pb, As, and Hg in the everyday environment may be toxic to human reproduction and development (9, 12-14). The main toxic effects of Cd, Pb, Hg, and As on the reproductive endocrine system comprise the promotion of oxidative stress, reduction of follicle-stimulating hormone, reduction of luteinizing hormone, reduction of follicular growth, promotion of follicular atresia and disruption of the estrous cycle (15)(16)(17)(18)(19)(20).…”

Early Life Environmental Exposure to Cadmium, Lead, and Arsenic and Age at Menarche: A Longitudinal Mother–Child Cohort Study in Bangladesh

“…Some animal studies have found a decrease in serum testosterone, estradiol, and progesterone following cadmium exposure, as well as increased lipid peroxidation and decreased antioxidant enzymes in the ovaries. 57 , 58 , 65 Others have reported an activation of steroidogenesis and increased serum estradiol and progesterone concentrations in the female offspring of cadmium-treated pregnant dams. 66 These conflicting results emphasize the need for further research on cadmium exposure and hormonal levels before and during reproductive maturation in large epidemiological studies with girls in the right developmental window.…”

“… 17 , 56 – 59 However, some of the experimental studies that administered cadmium orally have also reported later reproductive maturity in rats. 56 – 58 Later vaginal opening and an extended estrous cycle were observed in young females exposed after weaning 58 and in female offspring following exposure of the pregnant dams. 56 , 57 In contrast to the latter experimental studies, we did not observe any association between maternal erythrocyte cadmium during pregnancy and age at menarche.…”

Selenium prevents follicular granulosa cells from apoptosis induced by mercury through inhibition of ATF6/CHOP pathway in laying hens

“…Evidence has accumulated that many factors, including abrupt changes in the breeding environment and hazardous feed additives, can cause aberrant follicular development and follicular atresia in laying hens [19][20][21]. Hg is the most toxic in various feeds and showed the serious risk to animal reproductive performance.…”