Regular Abstract Submission
Dominika Gutkowska-Kawka, M.Ed
PhD student
Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, Olsztyn, Poland
Olsztyn, Warminsko-Mazurskie, Poland
Kisspeptins, encoded by the Kiss1 gene, are crucial regulators of the hypothalamic-pituitary-gonadal (HPG) axis. In females, kisspeptin-expressing neurons in the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV) have distinct roles in reproductive regulation. Neurons in the AVPV mediate estrogen-induced positive feedback, which is essential for the preovulatory surge of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH). In contrast, neurons in the ARC drive pulsatile GnRH/gonadotropin release, as well as folliculogenesis. Proper regulation of these processes is critical for normal reproductive function. Previously, we demonstrated that maternal undernutrition during lactation delays puberty onset and reduces ovarian follicle numbers in female offspring. This study investigates whether these reproductive deficits are associated with alterations in circulating estradiol levels and changes in the number of neurons expressing kisspeptin and estrogen receptor alpha (ERα), encoded by Esr1, in specific hypothalamic regions.
To address this, we employed a mouse model of maternal undernutrition during lactation. Newborn female mice (F1) were assigned to one of two experimental groups: (1) a control group (CON), in which dams had unrestricted access to food, and (2) a lactation undernutrition group (LUN), in which dams received 50% of the daily chow intake of the control mothers. Kiss1 and Esr1 mRNAs were visualized using the RNAscope in situ hybridization method, and the number of cells expressing these transcripts was quantified in the AVPV and ARC of 21-day-old female offspring. Additionally, we utilized transgenic mice expressing tdTomato fluorescent protein in kisspeptin neurons to visualize kisspeptin-expressing cells and performed immunofluorescence staining for ERα to assess co-expression.
No differences were observed in the number of Kiss1 or Esr1 mRNA-positive cells between the LUN and CON groups at weaning in either the AVPV or ARC, nor in the number of neurons co-expressing both transcripts. However, the AVPV of LUN females exhibited a greater number of ERα-expressing cells was detected in the AVPV of LUN females compared to controls. Furthermore, the proportion of tdTomato-positive kisspeptin neurons co-expressing ERα was higher in the ARC of LUN females, particularly in the caudal region.
These findings suggest that maternal undernutrition during lactation may alter estrogen signaling within the hypothalamic kisspeptin system in offspring. The increased co-expression of ERα in kisspeptin neurons in the ARC may represent a compensatory response to early-life nutritional stress, potentially affecting the sensitivity of these neurons to unsettled estradiol feedback. Given the critical role of kisspeptin and ERα in regulating GnRH release and reproductive function, these changes could have long-term consequences for the reproductive maturation and fertility of female offspring. Future studies should determine whether these alterations persist into adulthood. Additionally, further investigation of the mechanisms driving ERα expression changes may provide insight into the developmental plasticity of the HPG axis in response to early-life metabolic challenges.
Research supported by Polish National Science Centre [2018/31/B/NZ4/03527].