Puberty onset is delayed following uteroplacental insufficiency and occurs earlier with improved lactation and growth for pups born small

Abstract

Being born small programs adult diseases later in life, with the early postnatal growth rate in growth-restricted offspring playing a role in the reduction of the risk of disease in adulthood. In addition, early postnatal growth is critical for puberty onset (PO). Using cross-fostering, we determined the effects of growth restriction and prenatal and postnatal environments on PO and sex steroids. Bilateral uterine vessel ligation (Restricted) or sham surgery (Control), performed on Gestational Day 18 in Wistar-Kyoto rats induced fetal growth restriction. Control, Reduced (Control litter size reduced to five pups) and Restricted pups were cross-fostered onto different Control (normal lactation) or Restricted (impaired lactation) mothers on Day 1. The day of vaginal opening (females) and balanopreputial separation (males) characterised PO. Blood was sampled for sex steroid and leptin analysis. Restricted pups were born lighter than Controls (P < 0.05). PO was delayed by 3.4–4 days in Restricted-on-Restricted males and females (P < 0.05). Plasma leptin concentrations at PO were lower in both sexes in all groups compared with Restricted-on-Control and Control-on-Control (P < 0.05). PO occurred earlier in Restricted-on-Control (~2 days) with normal leptin concentrations and accelerated growth compared with Restricted-on-Restricted (P < 0.05). Testosterone concentrations were lower in male Restricted-on-Restricted than Control-on-Control at 6 months (P < 0.05). Restricted-on-Restricted females had lower progesterone at PO compared with Control-on-Control (P < 0.05). Female Restricted-on-Restricted had lower oestradiol, with Restricted-on-Control having higher testosterone concentrations at 6 months than Control-on-Control (P < 0.05). Growth restriction reduced postnatal growth and leptin concentrations, delaying PO in both sexes and programming altered sex steroids. This highlights the importance of the interaction between prenatal and postnatal growth in the programming of adult reproductive status.