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. Our findings revealed that DG treatment had no effect on genital differentiation or somatic growth. There were some indications that DG treatment suppressed juvenile play behavior and adult sexual motivation; however, male-typical sexual differentiation of reproductive behavior, sexual partner preference, and gonadotropin feedback remained unaffected and appeared to be fully masculinized and defeminized. DG-treated rams showed an increased LH response to GnRH stimulation and a decreased T response to human chorionic gonadotropin stimulation, suggesting impaired Leydig cell function and reduced T feedback. Both effects were reversed by cotreatment with T propionate. DG treatment also suppressed the expression of CYP17 messenger RNA, a key enzyme for T biosynthesis. Despite the mild hypogonadism induced by DG treatment, ejaculate volume, sperm motility, and sperm morphology were not affected. In summary, these results suggest that blocking GnRH during midgestation does not have enduring effects on brain sexual differentiation but does negatively affect the testes' capacity to synthesize T.

中文翻译：

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胎儿垂体睾丸抑制对雄性羊大脑性别分化和生殖功能的影响。

我们之前证明，用长效促性腺激素释放激素 (GnRH) 拮抗剂地加瑞克 (DG) 治疗妊娠第 62 天的胎羔可抑制妊娠中期的垂体-睾丸功能。本研究的目的是调查胎儿时期促性腺激素受损是否对成年雄性羊的性分化和生殖功能产生持久影响。我们评估了产前给予 DG（有或没有睾酮（T）替代）对成年公羊各种性二态性行为特征的影响，包括性伴侣偏好以及神经内分泌反应性和睾丸功能。我们的研究结果表明，DG 治疗对生殖器分化或体细胞生长没有影响。有一些迹象表明，DG 治疗抑制了青少年的游戏行为和成人的性动机；然而，男性典型的生殖行为、性伴侣偏好和促性腺激素反馈的性别分化并未受到影响，并且似乎完全男性化和非女性化。DG 处理的公羊表现出对 GnRH 刺激的 LH 反应增加，对人绒毛膜促性腺激素刺激的 T 反应减少，表明 Leydig 细胞功能受损，T 反馈减少。与丙酸T共同处理可逆转这两种效应。DG 处理还抑制了 CYP17 信使 RNA 的表达，CYP17 信使 RNA 是 T 生物合成的关键酶。尽管 DG 治疗引起轻度性腺功能减退，但射精量、精子活力和精子形态并未受到影响。总之，这些结果表明，在妊娠中期阻断 GnRH 不会对大脑性别分化产生持久影响，但会对睾丸合成 T 的能力产生负面影响。