Prenatal Androgen Treatment Does Not Alter the Firing Activity of Hypothalamic Arcuate Kisspeptin Neurons in Female Mice

Abstract

Prenatal androgen treatment does not alter the firing activity of hypothalamic arcuate kisspeptin neurons in female mice

GnRH Neuron Excitability and Action Potential Properties Change with Development But Are Not Affected by Prenatal Androgen Exposure

“…PNA-induced differences were confirmed in the present study; for mice in which electrophysiology was done at three weeks of age and in adulthood, these aspects were verified in littermates raised to adults as the PNA phenotype is consistent among littermates. As reported ( Roland and Moenter, 2011 ; Dulka and Moenter, 2017 ; Berg et al, 2018 ; Gibson et al, 2021 ), vaginal opening (VO) in the present study occurred at a younger age (unpaired, two-tailed Student’s t test; control n = 19 mice, PNA n = 16 mice) and lower body mass (two-tailed Mann–Whitney U test) in PNA females ( Fig. 1 A , B ; Table 1 ).…”

“…;Dulka and Moenter 2017;Berg, Silveira, and Moenter 2018;Gibson et al 2021), vaginal opening (VO) in the present study occurred at a younger age (unpaired, two-tailed Student's t-test; control n=19 mice, PNA n=16 mice) and lower body mass (two-tailed Mann Whitney U-test) in PNA females (Figure 1A-B, Table 1). Anogenital distance (AGD) was increased in adult PNA mice (unpaired, two-tailed Student's t-test, Figure 1C, Table…”

“…KNDy neurons express receptors for gonadal steroids ( Ruka et al, 2016 ; Silva et al, 2019 ), and thus serve as an important site for steroidal feedback modulation of GnRH neuron activity and a possible site of androgen action for the PNA phenotype ( Pielecka-Fortuna et al, 2011 ; Yeo et al, 2014 ; Adams et al, 2018 ; Nagae et al, 2021 ). KNDy neurons have been studied in PNA mice, and while both GABAergic and glutamatergic appositions to these cells are reduced in PNA mice ( Moore et al, 2021 ), neither the spontaneous firing rate nor the burst firing patterns of KNDy neurons change with development or with PNA treatment ( Gibson et al, 2021 ). KNDy-mediated changes in input to GnRH neurons could be generated by alterations in neuromodulator expression ( Goodman et al, 2013 ; Ahn et al, 2015 ).…”

Kisspeptin-neuron control of LH pulsatility and ovulation

“…Indeed, LH pulse frequency is useful for distinguishing between FHA and PCOS, as the two commonest pathological causes of secondary amenorrhoea (73). Possible mechanisms contributing to increased LH pulse frequency include loss of progesterone negative feedback (due to the opposing effects of androgens) and enhanced GABAergic drive to GnRH neurons (75)(76)(77). Indeed, LH production is increased in PNA mice subject to chemo-and opto-genetic activation of GABA neurons in the ARC, highlighting the stimulatory role of GABAergic neurons have on GnRH neurons (77).…”

“…Further, cfos expression was upregulated in ARC KP-neurons, indicating greater neuronal activation ( 78 ). However, not all features of PCOS are replicated in animal models of PCOS, as a recent study using PNA mice did not show that KNDy neuronal firing frequency was increased ( 75 ).…”