Foetal Loss and Enhanced Fertility Observed in Mice Treated with Zidovudine or Nevirapine

Abstract

BackgroundHealth concerns for HIV-infected persons on antiretroviral therapy (ART) have moved from morbidity to the challenges of long-term ART. We investigated the effect of Zidovudine or Nevirapine on reproductive capacity across two mouse generations.MethodsA prospective mouse study with drugs administered through one spermatogenic cycle. Mouse groups (16 males and 10 females) were given Zidovudine or Nevirapine for 56 days. Males were mated to untreated virgin females to determine dominant lethal effects. Twenty females (10 treated and 10 untreated) mated with the treated males per dose and gave birth to the F1 generation. Parental mice were withdrawn from drugs for one spermatogenic cycle and mated to the same dams to ascertain if effects are reversible. The F1 generation were exposed for another 56 days and mated to produce the F2 generation.ResultsFoetal loss was indicated in the dominant lethal assay as early as four weeks into drug administration to the males. At the first mating of the parental generation to produce the F1 generation, births from 10 dams/dose when the ‘father-only’ was exposed to Zidovudine (10, 100 and 250 mg/kg) was 3, 2 and 1 while it was 7, 1 and 4 respectively when ‘both-parents’ were exposed. Similarly births from the parental generation first mating when the ‘father-only’ was exposed to Nevirapine (5, 50 and 150 mg/kg) was 2, 2 and 0 while it was 6, 5 and 9 respectively when ‘both-parents’ were exposed. However, fertility was not significantly different neither by dose nor by the parental exposure. The F1 mice mated to produce the F2 generation recorded only one birth.ConclusionThe dominant lethal analysis showed foetal loss occurred when the “fathers-only” were treated while fertility was enhanced when “both-parents” were on therapy at the time of mating.

HAART and anti‐Koch’s impair sexual competence, sperm quality and offspring quality when used singly and in combination in male Wistar rats

“…These findings were associated with a reduced survival in offspring whose 'fathers' were treated with HAART, anti-Koch's and HAART + Anti-Koch's. These observations are in tandem with previous studies that documented reduced fertility capacity, lower litter size and weight and reduced survival of offspring of HAART and/or anti-Koch's-treated parents (Onwuamah et al, 2014;Shayakhmetova et al, 2015Shayakhmetova et al, , 2017. The reduced fertility success and fertility index are, at least partly, secondary to HAART-and Anti-Koch's-caused impaired sexual performance and poor sperm quality, while the observed lower litter size and weight might be due to an epigenetic modification with alterations in offspring quality.…”

Long‐Term Administration of Abacavir and Etravirine Impairs Semen Quality and Alters Redox System and Bone Metabolism in Growing Male Wistar Rats

“…HAART also caused decreased sperm count, motility, viability, and amount of sperm with normal morphology together with atrophy of seminiferous tubules and depletion of spermatogenic cells, especially of secondary spermatocytes [ 68 , 69 ]. HAART had a negative effect on the frequencies and latencies of various sexual behaviour parameters in male rats and impaired their fertility with a reduced number of offspring of male HAART-receiving rodents [ 68 , 70 ].…”

“…HAART had a negative effect on the frequencies and latencies of various sexual behaviour parameters in male rats 11 Oxidative Medicine and Cellular Longevity and impaired their fertility with a reduced number of offspring of male HAART-receiving rodents [68,70].…”

Effects of iron oxide nanoparticles as T2-MRI contrast agents on reproductive system in male mice

“…Given that the sperm damage was temporary and reversible, it may provide some important implications in clinical practice. It is well established that the spermatogenic cycle is critical for continuous sperm production, and the spermatogenic cycle of mice is eight weeks [ 66 ]. In consideration of that the reduction of sperm quantity and quality caused by the IONPs injection was able to completely return to the normal range within two weeks, we speculated that the sperm parameters would be free of abnormalities within a quarter of spermatogenic cycle in male patients who have received MRI examination with IONPs injection, in other words, the fertilized behavior of them was strongly recommended after about 2.5 weeks, which is a quarter of spermatogenic cycle of human beings (10 weeks) [ 67 ].…”