Neonatal exposure to genistein affects reproductive physiology and behavior in female and male Long-Evans rats

Abstract

The present study was designed to examine the effects of neonatal genistein exposure on measures of reproductive physiology and behavior. Approximately 24 h after birth, female and male Long-Evans rat pups were injected daily with genistein (150 µg, subcutaneous; n = 29) or olive oil (n = 23) between postnatal days 1 and 5. After weaning, we examined all subjects daily until they reached puberty (i.e. vaginal opening in female rats and preputial separation in male rats). For all female subjects, we also examined vaginal cytology. After monitoring estrous cyclicity, the female subjects were given the opportunity to interact with a gonadally intact male or a sexually receptive female rat on the day of behavioral estrus to assess sexual motivation (i.e. partner-preference test with and without physical contact), which has never been evaluated before. For all male subjects, we assessed the development of copulatory behavior and sexual motivation (partner-preference test without physical contact). Consistent with previous findings, we found that neonatal exposure to genistein did not affect puberty onset in female or male rats. However, female rats exposed to genistein displayed significantly more irregular estrous cycles than controls. Neonatal genistein exposure also altered the development of male copulatory behavior, as indicated by an increase in mount frequency and intromission frequency and shorter interintromission intervals. We extended previous findings confirming that neither female nor male sexual motivation was affected by neonatal genistein. The results of the present study have important implications for the development of reproductive physiology and behavior in human neonates exposed to genistein in soy-based baby formula.

Genistein Blunted Detrimental Effects of Polycystic Ovary Syndrome on the Ovarian Tissue of Rats by Improving Follicular Development and Gonadotropin Secretion

“…It has been postulated that genistein might directly affect the HPG axis and elevate gonadotropin-releasing hormone (GnRH) levels. The regulation of the HPG axis can support the production of gonadotropin hormones including FSH and LH ( Flynn et al ., 2000 ; Ren et al ., 2001 ; Zin et al ., 2013 ; Ali et al ., 2020 ). FSH decreases in rats with PCOS impairs follicular growth and maturation, leading to the formation of multiple cysts inside the ovarian tissue parenchyma.…”

Impact of Physiologically Relevant Genistein Exposure at Different Time Windows on Puberty Onset and Neuroendocrine Function in Female Rats

“…[ 9 ] Neonatal genistein exposure did not influence vaginal opening in rats. [ 10 ] Lactational genistein exposure at a high‐level accelerated puberty onset, while induced no effect at a low‐level. [ 11,12 ] Additionally, impact of genistein exposure at various pre‐pubertal stages on neuroendocrine function requires further elaboration.…”

“…[ 22 ] Here, neonatal exposure of genistein in olive oil did not affect vaginal opening, consistent with the recent study with similar dosage and vehicle. [ 10 ] Additionally, neonatal oral gavage in rats, and subcutaneous exposure in mice also showed no effect on vaginal opening. [ 23,24 ] Therefore, physiologically relevant genistein exposure at neonatal stage might not be a major contributor to the modulation of pubertal development in female rodents.…”

“…[ 26 ] Since 10 mg kg −1 genistein is physiologically relevant to human exposure, this dosage was adopted in this study, and significantly accelerated vaginal opening in lactational stage. [ 10,27 ] To date, this is the only study reporting the effect of physiologically relevant genistein exposure at different pre‐pubertal stages under paralleled experimental settings, and distinct differential interfering patterns of genistein were observed for lactational and neonatal exposures, suggesting that lactational stage might be a critical window for genistein to impact reproductive development in female rodents. Literatures describing the effect of EDCs exposure specifically at post‐weaning stage on puberty onset were majorly focused on industrially related EDCs.…”

Effects of Chronic Dietary Exposure to Phytoestrogen Genistein on Uterine Morphology in Mice

“…Most studies investigating the interaction of genistein with the reproductive system are based on acute exposure and are focused on prenatal or early life exposure. ,,, However, genistein exposure can happen at any time during the lifetime and, in some cases, is even more common toward the end of the reproductive phase, when women begin taking it to reduce menopausal symptoms. Previous research from our group tried to mimic human exposure by exposing adult intact females chronically to genistein in the diet.…”