Molecular mechanisms underlying the effects of hypo- and hyper-prolactinemia on spermatogenesis and fertility in male rats.

IF 5.4 2区医学 Q1 Medicine Journal of Endocrinological Investigation Pub Date : 2024-10-03 DOI:10.1007/s40618-024-02471-7

Sanketa Raut, Kushaan Khambata, Dipty Singh, Nafisa Huseni Balasinor

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Abstract

Purpose: Hypo- and hyper-prolactinemia have deleterious effects on male reproduction, yet there is a dearth of information regarding the underlying mechanisms. The aim of this study was to delineate the molecular mechanisms by which hypo- and hyper-prolactinemia affects spermatogenesis and fertility in male rats.

Methods: In vivo male rat models for hypo- and hyper-prolactinemia were established using dopamine receptor agonist, Bromocriptine (Brm), and antagonist, Fluphenazine (Flu), respectively. Effects on fertility and spermatogenesis were assessed by studying pre- and post-implantation loss, litter size, sperm parameters, hormonal profile, testicular histology, testicular cell population, and testicular transcriptome in rats.

Results: Treatment with Brm and Flu for 60 days led to subfertility, which was indicated by an increase in pre- and post-implantation loss and decrease in litter size, when mated with control female rats. Decreased sperm count was observed after both treatments, whereas reduced sperm motility was noted in Flu group. Serum FSH was unaffected, and LH was decreased by Flu treatment. Testosterone was decreased in both the groups, whereas estradiol was decreased in the Flu group. An arrest in spermatogenic cycle beyond round spermatids was observed in the Flu group. Additionally, testicular apoptosis in germ cells, mostly spermatocytes of Stage IX-XIV was noted in both the groups. Further, testicular RNA-Seq analysis revealed a total of 1539 and 824 differentially expressed genes/DEGs in Brm and Flu, respectively (Sequence Read Archive/SRA Database accession number: PRJNA1150513). Gene ontology and pathway analysis of DEGs highlighted enrichment of steroid metabolic pathway and ribosomal biogenesis pathway. Hub genes identified from the DEGs were validated by qPCR and the results showed that Uba52, Rps27a, Rpl23, Rps5, Rps16 were significantly down-regulated by Brm, whereas Rps27a, Rps29, Rps15, Rps27, Faul1 were significantly down-regulated by Flu.

Conclusion: Hypo- and hyper-prolactinemia leads to subfertility and decreased sperm parameters possibly through an effect on steroid metabolism and ribosomal biogenesis pathway. Therefore, maintaining prolactin levels in physiological range is crucial.

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低泌乳素血症和高泌乳素血症对雄性大鼠精子发生和生育能力影响的分子机制。

目的：低泌乳素血症和高泌乳素血症会对雄性生殖产生有害影响，但有关其潜在机制的信息却十分匮乏。本研究旨在阐明低泌乳素血症和高泌乳素血症影响雄性大鼠精子发生和生育能力的分子机制：方法：分别使用多巴胺受体激动剂溴隐亭（Brm）和拮抗剂氟奋乃静（Flu）建立雄性大鼠体内低泌乳素血症和高泌乳素血症模型。通过研究大鼠植入前后的损失、胎仔数、精子参数、激素谱、睾丸组织学、睾丸细胞群和睾丸转录组，评估了对生育能力和精子发生的影响：结果：与对照组雌性大鼠交配时，使用Brm和Flu治疗60天会导致亚不育，表现为受精前和受精后损失增加以及产仔数减少。两种处理后都观察到精子数量减少，而 Flu 组精子活力降低。血清 FSH 不受影响，而 LH 则因 Flu 处理而降低。两组睾酮均下降，而流感组雌二醇下降。观察到流感组的生精周期停滞在圆形精子之后。此外，两组患者的睾丸都出现了生精细胞凋亡，主要是第九至第十四阶段的精母细胞。此外，睾丸 RNA-Seq 分析显示，Brm 组和 Flu 组分别共有 1539 和 824 个差异表达基因/DEG（序列读取档案/SRA 数据库登录号：PRJNA1150513）。对 DEGs 的基因本体和通路分析显示，类固醇代谢通路和核糖体生物发生通路富集。通过 qPCR 验证了从 DEGs 中识别出的枢纽基因，结果显示，Uba52、Rps27a、Rpl23、Rps5、Rps16 被 Brm 显著下调，而 Rps27a、Rps29、Rps15、Rps27、Faul1 则被 Flu 显著下调：低泌乳素血症和高泌乳素血症可能通过影响类固醇代谢和核糖体生物发生途径导致不育和精子参数下降。因此，将催乳素水平维持在生理范围内至关重要。

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来源期刊

Journal of Endocrinological Investigation ENDOCRINOLOGY & METABOLISM-

CiteScore

8.10

自引率

7.40%

发文量

242

期刊介绍： The Journal of Endocrinological Investigation is a well-established, e-only endocrine journal founded 36 years ago in 1978. It is the official journal of the Italian Society of Endocrinology (SIE), established in 1964. Other Italian societies in the endocrinology and metabolism field are affiliated to the journal: Italian Society of Andrology and Sexual Medicine, Italian Society of Obesity, Italian Society of Pediatric Endocrinology and Diabetology, Clinical Endocrinologists’ Association, Thyroid Association, Endocrine Surgical Units Association, Italian Society of Pharmacology.