Centre for Neuroendocrinology, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand.
Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand.
Endocrinology. 2023 Mar 13;164(5). doi: 10.1210/endocr/bqad049.
Lactation in mammals is associated with a period of infertility, which serves to direct maternal metabolic resources toward caring for the newborn offspring rather than supporting another pregnancy. This lactational infertility is characterized by reduced pulsatile luteinizing hormone (LH) secretion and lack of ovulation. The mechanisms mediating suppression of LH secretion during lactation are unclear. There are potential roles for both hormonal cues such as prolactin and progesterone, and pup-derived cues such as suckling, on the inhibition of reproduction. To enable future studies using transgenic animals to investigate these mechanisms, in the present study our aim was to characterize lactational infertility in mice, and to investigate the effect of removing pup-derived cues on LH secretion, time to ovulation, and kisspeptin immunoreactivity. We first confirmed that C57BL/6J mice experience prolonged anestrus during lactation, which is dependent on establishment of lactation, as removal of pups the day of parturition led to immediate resumption of pulsatile LH secretion and normal estrous cycles. Once lactation is established, however, the lactational anestrus persisted for several days even after premature removal of pups. Pharmacological suppression of prolactin following premature weaning significantly reduced this period of lactational infertility. Progesterone does not appear to play a significant role in the suppression of fertility during lactation in mice, as levels measured during lactation were not different from nonpregnant mice. These data suggest that prolactin plays a key role in mediating anestrus during early lactation in mice, even in the absence of the suckling stimulus.
哺乳动物的哺乳期与不孕期有关，这有助于将母体代谢资源导向照顾新生后代，而不是支持另一次怀孕。这种哺乳期不孕的特征是促黄体生成素（LH）分泌减少和无排卵。介导哺乳期 LH 分泌抑制的机制尚不清楚。催乳素和孕激素等激素线索，以及哺乳等幼崽线索，都有可能在抑制生殖方面发挥作用。为了使未来使用转基因动物的研究能够调查这些机制，在本研究中，我们的目的是描述小鼠的哺乳期不孕，并研究去除幼崽线索对 LH 分泌、排卵时间和 kisspeptin 免疫反应的影响。我们首先证实，C57BL/6J 小鼠在哺乳期经历长时间的无发情期，这取决于哺乳期的建立，因为在分娩当天去除幼崽会立即恢复脉冲式 LH 分泌和正常发情周期。然而，一旦建立了哺乳期，即使在过早去除幼崽后，哺乳期的无发情期仍会持续数天。过早断奶后抑制催乳素的药物显著减少了哺乳期不孕的时间。孕激素在小鼠哺乳期抑制生育方面似乎没有发挥重要作用，因为哺乳期测量的水平与未怀孕的小鼠没有不同。这些数据表明，催乳素在介导小鼠哺乳期早期的无发情期方面发挥着关键作用，即使在没有哺乳刺激的情况下也是如此。
