Unraveling the impact of hyperleptinemia on female reproduction: insights from transgenic pig model

KIZ OpenIR

	Unraveling the impact of hyperleptinemia on female reproduction: insights from transgenic pig model
	Jamal, MA; Cheng, YX; Jiao, DL; Cheng, W; Zou, D; Wang, X; Wei, TY; Guo, JX; Xu, KX; Zhao, H; Pu, SX; Yang, C; Qing, YB; Jia, BY; Li, HH; Zhao, RS; Zhao, HY; Wei, HJ
	2024
发表期刊	BIOL RES
ISSN	0716-9760
卷号	57 期号:1
摘要	BackgroundInfertility is a growing global health concern affecting millions of couples worldwide. Among several factors, an extreme body weight adversely affects reproductive functions. Leptin is a well-known adipokine that serves as an endocrine signal between adiposity and fertility. However, the exact mechanisms underlying the effects of high leptin level on female reproduction remain unclear.MethodsTransgenic pigs overexpressing leptin (female) were produced by backcrossing and screened for leptin overexpression. The growth curve, fat deposition, reproductive performance, apoptosis, serum hormones and cholesterol production, RNA sequencing, and single-nucleus RNA sequencing (snRNA-seq) of the leptin-overexpressing pigs and wild-type group were evaluated.ResultsTransgenic pigs overexpressing leptin (female) were obtained, which exhibited significantly reduced body weight, body size, and back fat thickness. These pigs manifested a late onset of puberty (330 +/- 54.3 vs. 155 +/- 14.7 days), irregular estrous behavior characterized by increased inter-estrous interval (29.2 +/- 0 vs. 21.3 +/- 0.7 days), and more number of matings until pregnancy (at least 3 times). This reproductive impairment in leptin pigs was related to hormonal imbalances characterized by increased levels of FSH, LH, prolactin, E2, P4, and TSH, altered steroidogenesis such as increased levels of serum cholesterol esters along with steroidogenic markers (StAR, CYP19A), and ovarian dysfunctions manifested by neutrophilic infiltration and low expression of caspase-3 positive cells in the ovaries. Moreover, bulk RNA sequencing of the ovaries also revealed neutrophilic infiltration followed by upregulation of inflammation-related genes. Furthermore, snRNA-seq reflected that leptin overexpression triggered immune response, suppressed follicle development and luteinization, resulting in metabolic dysfunction and hormone imbalance in the ovary.ConclusionsLow body weight in leptin overexpressing pigs adversely affects the reproductive performance, causing delayed puberty, irregular estrous cycles, and reduced breeding efficiency. This is linked to metabolic imbalances, an increased immune response, and altered ovarian functions. This study provides a theoretical basis for the complex mechanisms underlying leptin, and infertility by employing leptin-overexpressing female pigs.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14697
专题	昆明动物研究所
推荐引用方式 GB/T 7714	Jamal, MA,Cheng, YX,Jiao, DL,et al. Unraveling the impact of hyperleptinemia on female reproduction: insights from transgenic pig model[J]. BIOL RES,2024,57(1).
APA	Jamal, MA.,Cheng, YX.,Jiao, DL.,Cheng, W.,Zou, D.,...&Wei, HJ.(2024).Unraveling the impact of hyperleptinemia on female reproduction: insights from transgenic pig model.BIOL RES,57(1).
MLA	Jamal, MA,et al."Unraveling the impact of hyperleptinemia on female reproduction: insights from transgenic pig model".BIOL RES 57.1(2024).

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