KNDy Neurons and the Control of the Gonadotropic Axis in the Midgestation Fetal Sheep.

KNDy neurons, located in the hypothalamic arcuate nucleus, coexpress kisspeptin (Kiss), neurokinin B, and dynorphin and play a crucial role in regulating GnRH/LH secretion in midgestation sheep fetuses. We hypothesize that KNDy-GnRH signaling is established during midgestation, with negative feedback acting through KNDy neurons regulating testosterone levels needed for brain masculinization in male fetuses. We used immunofluorescence histochemistry to assess the effect of chemical castration with the GnRH antagonist degarelix on arcuate KNDy neurons in fetal sheep.

Anatomic distribution of kisspeptin neurons in the adult sheep amygdala: Associations with sex, estrogen receptor alpha, androgen receptor, and sexual partner preference.

Kisspeptin neurons are primarily known for regulating reproductive function by stimulating hormone release that controls puberty and fertility. While typically associated with the hypothalamus, recent research suggests their presence in other brain regions, including the amygdala. The amygdala, crucial for emotional processing and social behaviors, consists of various nuclei.

Effect of Fetal Pituitary-Testes Suppression on Brain Sexual Differentiation and Reproductive Function in Male Sheep.

We previously demonstrated that treating fetal lambs on gestational day 62 with the long-acting gonadotrophin-releasing hormone (GnRH) antagonist degarelix (DG) suppresses pituitary-testicular function during midgestation. The objective of this study was to investigate whether impaired gonadotrophic drive during this fetal period has enduring effects on sexual differentiation and reproductive function in adult male sheep. We assessed the effects of prenatal administration of DG, with or without testosterone (T) replacement, on various sexually dimorphic behavioral traits in adult rams, including sexual partner preferences, as well as neuroendocrine responsiveness and testicular function.

Identification of differential hypothalamic DNA methylation and gene expression associated with sexual partner preferences in rams.

The sheep is a valuable model to test whether hormone mechanisms that sexually differentiate the brain underlie the expression of sexual partner preferences because as many as 8% of rams prefer same-sex partners. Epigenetic factors such as DNA methylation act as mediators in the interaction between steroid hormones and the genome. Variations in the epigenome could be important in determining morphological or behavior differences among individuals of the same species.

The GnRH Antagonist Degarelix Suppresses Gonadotropin Secretion and Pituitary Sensitivity in Midgestation Sheep Fetuses.

The specific role of gonadotropin-releasing hormone (GnRH) on brain sexual differentiation remains unclear. To investigate whether gonadotropin and, in turn, testosterone (T) secretion is regulated by GnRH during the critical period for brain differentiation in sheep fetuses, we attempted to selectively suppress pituitary-testicular activation during midgestation with the long-acting GnRH antagonist degarelix. Fetuses received subcutaneous injections of the antagonist or vehicle on day 62 of gestation.

Role for Kisspeptin and Neurokinin B in Regulation of Luteinizing Hormone and Testosterone Secretion in the Fetal Sheep.

Evidence suggests that the hypothalamic-pituitary-gonadal (HPG) axis is active during the critical period for sexual differentiation of the ovine sexually dimorphic nucleus, which occurs between gestational day (GD) 60 and 90. Two possible neuropeptides that could activate the fetal HPG axis are kisspeptin and neurokinin B (NKB). We used GD85 fetal lambs to determine whether intravenous administration of kisspeptin-10 (KP-10) or senktide (NKB agonist) could elicit luteinizing hormone (LH) release.

Excess Testosterone Exposure Alters Hypothalamic-Pituitary-Testicular Axis Dynamics and Gene Expression in Sheep Fetuses.

Prenatal exposure to excess androgen may result in impaired adult fertility in a variety of mammalian species. However, little is known about what feedback mechanisms regulate gonadotropin secretion during early gestation and how they respond to excess T exposure. The objective of this study was to determine the effect of exogenous exposure to T on key genes that regulate gonadotropin and GnRH secretion in fetal male lambs as compared with female cohorts.

Effect of Testosterone on Neuronal Morphology and Neuritic Growth of Fetal Lamb Hypothalamus-Preoptic Area and Cerebral Cortex in Primary Culture.

Testosterone plays an essential role in sexual differentiation of the male sheep brain. The ovine sexually dimorphic nucleus (oSDN), is 2 to 3 times larger in males than in females, and this sex difference is under the control of testosterone. The effect of testosterone on oSDN volume may result from enhanced expansion of soma areas and/or dendritic fields.