PMID- 37993510 OWN - NLM STAT- MEDLINE DCOM- 20231124 LR - 20231220 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 13 IP - 1 DP - 2023 Nov 22 TI - Conditional Oprk1-dependent Kiss1 deletion in kisspeptin neurons caused estrogen-dependent LH pulse disruption and LH surge attenuation in female rats. PG - 20495 LID - 10.1038/s41598-023-47222-5 [doi] LID - 20495 AB - The gonadotropin-releasing hormone (GnRH) pulse and surge are considered to be generated by arcuate kisspeptin/neurokinin B/dynorphin A (KNDy) neurons and anteroventral periventricular nucleus (AVPV) kisspeptin neurons, respectively, in female rodents. The majority of KNDy and AVPV kisspeptin neurons express kappa-opioid receptors (KORs, encoded by Oprk1) in female rodents. Thus, this study aimed to investigate the effect of a conditional Oprk1-dependent Kiss1 deletion in kisspeptin neurons on the luteinizing hormone (LH) pulse/surge and fertility using Kiss1-floxed/Oprk1-Cre rats, in which Kiss1 was deleted in cells expressing or once expressed the Oprk1/Cre. The Kiss1-floxed/Oprk1-Cre female rats, with Kiss1 deleted in a majority of KNDy neurons, showed normal puberty while having a one-day longer estrous cycle and fewer pups than Kiss1-floxed controls. Notably, ovariectomized (OVX) Kiss1-floxed/Oprk1-Cre rats showed profound disruption of LH pulses in the presence of a diestrous level of estrogen but showed apparent LH pulses without estrogen treatment. Furthermore, Kiss1-floxed/Oprk1-Cre rats, with Kiss1 deleted in approximately half of AVPV kisspeptin neurons, showed a lower peak of the estrogen-induced LH surge than controls. These results suggest that arcuate and AVPV kisspeptin neurons expressing or having expressed Oprk1 have a role in maintaining normal GnRH pulse and surge generation, the normal length of the estrous cycle, and the normal offspring number in female rats. CI - (c) 2023. The Author(s). FAU - Nagae, Mayuko AU - Nagae M AD - Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 464-8601, Japan. AD - Section of Mammalian Transgenesis, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, 444-8787, Japan. FAU - Yamada, Koki AU - Yamada K AD - Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 464-8601, Japan. FAU - Enomoto, Yuki AU - Enomoto Y AD - Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 464-8601, Japan. FAU - Kometani, Mari AU - Kometani M AD - Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 464-8601, Japan. FAU - Tsuchida, Hitomi AU - Tsuchida H AD - Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 464-8601, Japan. FAU - Panthee, Arvinda AU - Panthee A AD - Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 464-8601, Japan. FAU - Nonogaki, Miku AU - Nonogaki M AD - Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 464-8601, Japan. FAU - Matsunaga, Nao AU - Matsunaga N AD - Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 464-8601, Japan. FAU - Takizawa, Marina AU - Takizawa M AD - Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 464-8601, Japan. FAU - Matsuzaki, Sena AU - Matsuzaki S AD - Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 464-8601, Japan. FAU - Hirabayashi, Masumi AU - Hirabayashi M AD - Section of Mammalian Transgenesis, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, 444-8787, Japan. FAU - Inoue, Naoko AU - Inoue N AD - Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 464-8601, Japan. FAU - Tsukamura, Hiroko AU - Tsukamura H AD - Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 464-8601, Japan. htsukamura@nagoya-u.jp. FAU - Uenoyama, Yoshihisa AU - Uenoyama Y AD - Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 464-8601, Japan. uenoyama@nagoya-u.jp. LA - eng GR - JP22J10728/Japan Society for the Promotion of Science/ GR - JP22KJ1548/Japan Society for the Promotion of Science/ GR - JP19H03103/Japan Society for the Promotion of Science/ GR - JP23H02362/Japan Society for the Promotion of Science/ GR - JP21H05031/Japan Society for the Promotion of Science/ GR - JP21K19186/Japan Society for the Promotion of Science/ GR - JP20H03127/Japan Society for the Promotion of Science/ GR - JP22K19245/Japan Society for the Promotion of Science/ PT - Journal Article DEP - 20231122 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Kisspeptins) RN - 9002-67-9 (Luteinizing Hormone) RN - 0 (Estrogens) RN - 33515-09-2 (Gonadotropin-Releasing Hormone) RN - 86933-75-7 (Neurokinin B) RN - 74913-18-1 (Dynorphins) RN - 0 (Kiss1 protein, rat) SB - IM MH - Rats MH - Female MH - Animals MH - *Kisspeptins/metabolism MH - *Luteinizing Hormone/pharmacology MH - Estrogens/pharmacology MH - Gonadotropin-Releasing Hormone/metabolism MH - Neurokinin B/genetics/metabolism MH - Dynorphins/metabolism MH - Neurons/metabolism MH - Arcuate Nucleus of Hypothalamus/metabolism PMC - PMC10665460 COIS- The authors declare no competing interests. EDAT- 2023/11/23 00:42 MHDA- 2023/11/24 06:43 PMCR- 2023/11/22 CRDT- 2023/11/22 23:32 PHST- 2023/07/05 00:00 [received] PHST- 2023/11/10 00:00 [accepted] PHST- 2023/11/24 06:43 [medline] PHST- 2023/11/23 00:42 [pubmed] PHST- 2023/11/22 23:32 [entrez] PHST- 2023/11/22 00:00 [pmc-release] AID - 10.1038/s41598-023-47222-5 [pii] AID - 47222 [pii] AID - 10.1038/s41598-023-47222-5 [doi] PST - epublish SO - Sci Rep. 2023 Nov 22;13(1):20495. doi: 10.1038/s41598-023-47222-5.