Developmental Toxicity in Mice Following Paternal Exposure to Di-N-Butyl-Phthalate (DBP)

Objective The aim of the present study was to investigate the effects of paternal Di‐N‐butyl‐phthalate （DBP） exposure pre‐ and postnatally on F1 generation offspring,and prenatally on F2 generation offspring.Methods Male mice were exposed to either 500 mg/kg or 2 000 mg/kg of DBP for 8 weeks,and mated with non‐exposed females.Three‐quarters of the females were sacrificed a day prior to parturition,and examined for the number of living and dead implantations,and incidence of gross malformations.Pups from the remaining females were assessed for developmental markers,growth parameters,as well as sperm quantity and quality.Results There were no changes in the fertility of parents and in intrauterine development of the offspring.Pups of DBP‐exposed males demonstrated growth‐retardation.Following paternal exposure to 500 mg/kg bw of DBP,there were almost twice the number of males than females born in the F1 generation.F1 generation females had a 2.5‐day delay in vaginal opening.Paternal exposure to 2 000 mg/kg bw of DBP increased the incidence of sperm head malformations in F1 generation males;however,there were no changes in the fertility and viability of foetuses in the F2 generation.Conclusion Paternal DBP exposure may disturb the sex ratio of the offspring,delay female sexual maturation,and deteriorate the sperm quality of F1 generation males.

Risk factors for hypospadias in China

This case-controlled study was designed to evaluate the association between various baseline parental factors and the risk of hypospadias in China. Patients were selected from tertiary referral hospitals in Anhui, a province in mid-eastern China. A questionnaire was given to the parents of each patient. The final database included 193 cases and 835 controls. The incidence of additional coexistent anomalies was 13.0%, primarily cryptorchidism （9.8%）. Ten patients （5.1%） were from families with genital anomaly, including five families （2.6%） with hypospadias. The risks of hypospadias was higher for children of mothers 〉 35 （odds ratio [OR] =1.47） and 〈 18 （OR = 2.95） years of age, and in mothers who had consumed alcohol （OR = 2.67）, used drugs （OR = 1.53） and had an infection （OR = 1.87） during pregnancy. The risk of hypospadias was also higher when mothers （OR = 1.68） and fathers （OR = 1.74） were engaged in agriculture. Other factors assessed were not associated with the risk of hypospadias.

Developmental origins of health and disease: Impact of paternal nutrition and lifestyle

Most epidemiological and experimental studies have focused on maternal influences on offspring’s health.The impact of maternal undernutrition,overnutrition,hypoxia,and stress is linked to adverse offspring outcomes across a range of systems including cardiometabolic,respiratory,endocrine,and reproduction among others.During the past decade,it has become evident that paternal environmental factors are also linked to the development of diseases in offspring.In this article,we aim to outline the current understanding of the impact of male health and environmental exposure on offspring development,health,and disease and explore the mechanisms underlying the paternal programming of offspring health.The available evidence suggests that poor paternal pre-conceptional nutrition and lifestyle,and advanced age can increase the risk of negative outcomes in offspring,via both direct(genetic/epigenetic)and indirect(maternal uterine environment)effects.Beginning at preconception,and during utero and the early life after birth,cells acquire an epigenetic memory of the early exposure which can be influential across the entire lifespan and program a child’s health.Potentially not only mothers but also fathers should be advised that maintaining a healthy diet and lifestyle is important to improve offspring health as well as the parental health status.However,the evidence is mostly based on animal studies,and well-designed human studies are urgently needed to verify findings from animal data.