Pre-Weaning Overfeeding Promotes Prepubertal Obesity and Evokes Sexual Dysfunction in Young Adult Rats

Obesity in early life can contribute to several health issues in adulthood, including diabetes, high blood pressure, and high cholesterol, and these conditions are associated with sexual dysfunction. Here, we hypothesized that pre-weaning overfeeding can have long lasting effects on body fat distribution and erectile function that will be observed in young adult males. On postnatal day (PND 1), Wistar rats were separated into two groups: normal litter (NL) with 10 pups per dam, or small litter (SL) with 3 pups per dam. Male rats (n = 8-10 per group) were then assessed at two different time points: during the prepubertal stage (PND 40) and in adulthood (PND 120). Erectile function was assessed only after sexual maturation (i.e., PND 120). Body weight, retroperitoneal and perigonadal adipose tissue (fat pad weight/100g of the body) were evaluated. Following euthanasia at PND 120, the corpus cavernosum (CC) was removed to perform functional studies using a strip myograph. Contractile and relaxation responses were evaluated by electrical field stimulation (EFS) and concentration-response curves (CRC) to phenylephrine [Phe, 1nM-30μM, millinewton (mN)] or acetylcholine (Ach 1nM-30μM, % relaxation) were performed. At the prepubertal stage, SL rats had higher body weight (NL 149±3 vs. SL 186±5, g, p<0.05), and increased retroperitoneal (NL 0.17±0.01 vs. SL 0.32±0.03, g/100g, p<0.05) and perigonadal (NL 0.38± 0.02 vs. SL 0.45±0.03, g/100g, p<0.05) adipose tissue. At PND 120, SL group presented increased body weight (NL 534.2.7±13 vs. SL 631.6±10, g, p<0.05), retroperitoneal (NL 1.31±0.11 vs. SL 1.82±0.14, g/100g, p<0.05) and perigonadal (NL 1.74±0.10 vs. SL 2.18±0.15, g/100g, p<0.05) adipose tissue when compared with NL group. The CC of SL rats at PND 120 had increased contraction induced by EFS for all frequencies (1 Hz: NL 0.5 ± 0.2 mN vs. SL 0.9 ± 0.2 mN; 4 Hz: NL 1.2 ± 0.3 mN vs. SL 1.8 ± 0.2 mN; 16 Hz: NL 1.9 ± 0.4 mN vs. SL 3 ± 0.4 mN), whereas the relaxation was decreased in SL (1 Hz: NL 0.77 ± 0.18% vs. SL 0.27 ± 0.09%; 4 Hz: NL 2.48 ± 0.26% vs. SL 1.36 ± 0.41%; 16 Hz: NL 3.06 ± 0.28% vs. SL 2.39 ± 0.53%). CRC showed increased contractile response to Phe (Emax NL 2.3±0.3 vs. SL 3.8± 0.6, mN, p=0.05) and reduced potency of ACh (pEC50 NL 6.4±0.6 vs. SL 4.9±0.7, mN, p=0.1) in the CC of SL. Incubation with indomethacin (10μM) abolished the differences in the contractile response induced by EFS or Phe between SL and NL, suggesting a heightened inflammatory response. Moreover, the CC of SL rats presented increased expression of Phospho-p44/42 MAPK (NL 0.9±0.25 vs. SL 1.3±0.11, p=0.2). Finally, proteome profiler cytokine array of serum samples from SL animals showed increased circulating levels of cytokines and chemokines associated with obesity, aging, and vascular dysfunction. Together, these data suggest that early prepubertal obesity has long-lasting negative implications on sexual function in young adulthood. National Institutes of Health (NIH); American Heart Association (AHA); Fulbright Program. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.