Prenatal Androgen Exposure Alters Male Sperm Count, Motility, and Offspring Growth but does not affect Fertility.

SILVANA ROCIO FERREIRA; GISELLE ADRIANA ABRUZZESE; AIME FLORENCIA SILVA; MARIA JOSÉ FERRER; ALICIA BEATRIZ MOTTA

modalidad virtual

Congreso; 4th Meeting of Latin American DOHaD Chapter; 2020

Background: Prenatal androgen exposure affects females´ reproductive and metabolic parameters, leading to phenotypes that resemble those of Polycystic ovary syndrome (PCOS) in women. PCOS is a multifactorial pathology, and prenatal androgen excess is considered one of the main factors contributing to the syndrome development in females. In the past years, it has been reported that male relatives of PCOS women may show altered metabolic and endocrine parameters. However, few studies had focused on the effects of prenatal androgen exposure on males and the intergenerational effect of androgens. This study aimed to investigate the impact of androgen exposure on males´ reproductive parameters and outcomes and the possible paternal contribution to intergenerational effects until neonatal development. Methods: Pregnant females (F0) were treated daily on gestational days 16 to 19 with a dose of 1mg of testosterone. A control group was daily injected with vehicle in the same window of injection. The offspring from androgenized mothers were the prenatally androgenized (PA) group, and those from mothers injected with vehicle were the control group (C). Male offspring (F1) weight was weekly measured from day 7 to adulthood (90 days of life). We performed a glucose tolerance test during adulthood, and after-euthanasia epididymis and testis were weighted. We also analyzed epididymal sperm count and motility analysis, and morphological studies were assessed. Spermatozoa were classified as normal or abnormal. Morphological abnormalities were divided into head defects (considering amorphous head, head with amorphous curvature or curvature absence), and tail defects were analyzed only considering the presence of simple or double tail or the absence of the tail. The fertility rate was evaluated. For this, PA-F1 and C-F1 males were mated with naïve females. A randomly selected group from both treatments was euthanized at 14 days of pregnancy and embryo weight, and embryo crown-rump length was assessed. Another group was left to deliver, and offspring (F2) parameters were analyzed at postnatal day 6 (PND6).Results: No differences were found in the growth curve nor the glucose tolerance test in males from the PA-F1 groups as compared to C-F1. PA-F1 males showed decreased average testis weight and lower sperm motility and count than C-F1 males. No differences were found regarding the percentage of abnormal sperm in PA-F1 animals as compared to C-F1. Moreover, fertility studies revealed no alterations in the mating index, the fecundity and fertility index of PA males if compared to controls. Regarding F2, we found no differences in embryos´ weight. However, embryos from PA-F1 fathers showed an increased embryo crown-rump length compared to the offspring of C-F1 fathers. At PND6, F2 offspring from PA-F1 males showed decreased body weight and body length in females and males. No differences in the anogenital distance were found between F2 from PA-F1 males and those from C-F1.Conclusion: Our results show that prenatal androgen exposure impairs male sperm parameters without affecting fertility rate. Moreover, the offspring of PA-F1 fathers showed an altered growth, with increased length during intrauterine development and a decreased body weight and length at the neonatal stage in both sexes.