Ascorbic acid co-administered with rosuvastatin reduces reproductive impairment in the male offspring from male rats exposed to the statin at pre-puberty

Abstract

Obesity during childhood and adolescence is closely related to dysfunctions on lipid profile in children. Rosuvastatin is a statin that decreases serum total cholesterol. Ascorbic acid is an important antioxidant compound for male reproduction. Pre-pubertal male rats were distributed into six experimental groups that received saline solution 0.9% (vehicle), 3 or 10 mg/kg/day of rosuvastatin, 150 mg/day of ascorbic acid, or 3 or 10 mg/kg/day of rosuvastatin co-administered with 150 mg/day of ascorbic acid by gavage from post-natal day (PND)23 until PND53. Rats were maintained until adulthood and mated with nulliparous females to obtain the male offspring, whose animals were evaluated at adulthood in relation to reproductive parameters. This study is a follow up of a previous paper addressing potential effects on F0 generation only (Leite et al., 2017). Male offspring from rosuvastatin-exposed groups showed increased sperm DNA fragmentation, androgen depletion and impairment on the testicular and epididymal structure. Ascorbic acid coadministered to the fathers ameliorated the reproductive damage in the offspring. In summary, paternal exposure to rosuvastatin may affect the reproduction in the male offspring; however, paternal supplementation with ascorbic acid was able to reduce the reproductive impairment in the male offspring caused by statin treatment to the fathers.

Reproductive outcomes in rat female offspring from male rats co-exposed to rosuvastatin and ascorbic acid during pre-puberty

“…Ascorbate, an intracellular form of ascorbic acid, regulates DNA demethylation and histone demethylation (Young, Zuchner, and Wang 2015), thus presenting an important epigenetic role. Leite et al (2018) found that paternal supplementation with AA ameliorated the reproductive damage in the male offspring attributed to rosuvastatin, probably due to AA action on inhibition of genetic and epigenetic changes in paternal spermatozoa.…”

“…Previous studies suggested epigenetic changes were attributed to statin exposure (Bustan and Jawad 2017;Leite et al 2018). Bustan and Jawad (2017) associated paternal or maternal exposure to atorvastatin or rosuvastatin with alterations in fertility in their offspring.…”

“…Bustan and Jawad (2017) associated paternal or maternal exposure to atorvastatin or rosuvastatin with alterations in fertility in their offspring. In addition, Leite et al 2018 indicated that prepubertal male rats exposed to rosuvastatin showed impairment to the reproductive system in the male offspring.…”

The effect of statins on semen parameters in patients with hypercholesterolemia: A systematic review

“…20 Inconsistent data exist for rosuvastatin on this context. [21][22][23] Interestingly, transient azoospermia has been reported in a male patient with oligoasthenozoospermia after rosuvastatin administration. Spermatozoa reappeared in the ejaculated semen at two weeks after drug withdrawal and increased to baseline levels at 16 weeks.…”

“…[15][16][17] Previous studies found that SARS, 1 of the 3 epidemic coronaviruses to emerge in the past 20 years and that shows similar clinical presentations to COVID-19, 18 could cause orchitis 19 and focal testicular atrophy. 20 Considering the tens of millions of COVID-19 cases and that men are more vulnerable to COVID-19 than women, [21][22][23] it is imperative to determine the effect of COVID-19 on male reproduction. 24 Several studies have been performed on this topic.…”