New Search

Export article
Open Access

A Mini-Review on Candidate Genes for Regulation of Reproduction and Puberty Onset

Iffat Fatima, Abdul-Aziz Khan, Zainab Rehman
Published: 26 November 2018
Perceptions in Reproductive Medicine , Volume 3, pp 1-3; doi:10.31031/prm.2018.03.000552

Abstract: Iffat Fatima*, Abdul-Aziz Khan and Zainab Rehman Iffat Fatima, Department of Animal Sciences, Pakistan *Corresponding author: Iffat Fatima, Laboratory of Physiology, Department of Animal Sciences, Pakistan Submission: August 15, 2018;Published: November 26, 2018 DOI: 10.31031/PRM.2018.03.000552 ISSN: 2640-9666Volume3 Issue1 Initiation and progression of puberty is a critical event for mammals. Various neuronal and hormonal cues are required for normal onset of puberty. GnRH is the major hormone involved in regulation of these mechanisms. Regulation of this complex process is controlled by multiple genes which encode respective proteins used as stimulatory inputs like glutamate, kisspeptin etc. or inhibitory inputs. These genes include KISS1/Kiss1, KISSR, Kissr, Tac3, TacR3, LEP, EAP1 etc. Findings of different studies are reviewed. Significance of Tac3 and TacR3 is evaluated by administering its agonist senktide in prepubertal female rats which results in increased LH secretion. Moreover, expression of Kiss1 gene is more sensitive to negative feedback effect of sex-steroids early in puberty than Tac2 expression. EAP1 is essential for normal menstrual cycle in female monkeys. LIN28A and LIN28B are considered essential for pubertal development and are good candidate genes for monogenic ICCP. Similarly, mutations in Leptin gene (LEP) result in abnormalities including obesity, delayed puberty and CDGP etc.. Keywords:Puberty genes; Hypogonadotropic hypogonadism (IHH); Kisspeptin Abbreviations: IHH: Ideopathic Hypogonadotropic Hypogonadism; CCP: Central Precocious Puberty; ICCP: Ideopathic Central Precocious Puberty; CDGP: Constitutional Delay in Growth and Puberty; LEP: Leptin Gene The pulsatile release of GnRH from hypothalamus is essential for induction of initiation and progression of puberty in mammals. A network of neurons located in the medial basal hypothalamus (MBH) in primates is the source of GnRH release into portal vessels which makes a connection between brain and pituitary gland. Alterations in neuronal and glial inputs to GnRH producing neurons control its periodic secretion. Regulatory mechanisms of this process at transcriptional level are not well understood, but it is apparent that several genes are involved [1]. Glutamate and kisspeptin signaling provides excitatory input whereas, (GABA) ergic and opiatergic neurons constitute inhibitory neuronal network. Glial cells mediate GnRH secretion via intercellular communication though various growth factors. Regulation of pubertal process by functionally linked genes provides the polygenetic evidence rather than specified by a single gene [2]. Evidences from various puberty related defects support the significance of the respective genes in puberty onset. These include GnRH1, GnRHR, KISS1, KISS1R, Tac3, TacR3, Eap1, Lin28, LH receptor gene and FSH receptor gene etc. It can be exemplified by loss of function mutations in KISSR in humans result in IHH whereas, gain of function mutations can lead to CPP (central precocious puberty) [3]. Previous studies reveal that pubertal onset involves additive effect of various genes however monogenic basis of Ideopathic central precocious puberty is also suggested [4]. Kisspeptin has key role in the onset of puberty. It stimulates Gonadotropin releasing hormone (GnRH) from the GnRH neurons present in the hypothalamus. Kisspeptin works through its receptor named GpR54 [5]. Mutations in genes encoding Kisspeptin and its receptor provide the evidence for its role in puberty onset. This is revealed by infertility and hypogonadotropic hypogonadism resulted due to mutations in these genes. Moreover, exogenous administration of GnRH compensates the effect of mutation of KISS1R/kiss1r. Mayer et al. [6], found that in spite of ablation of Kiss1 expressing cells in brain of female mice, normal puberty onset and fertility is exhibited, challenging the significance of Kiss1 neurons for reproduction. Differential requirement of Kiss1 expression for successful reproduction in male and female mice: Popa et al. [7], devised an experiment to prove the significance of kisspeptin genes, according to which normal reproduction can be supported by minute amount of kisspeptin. In this experiment mice (Kiss1-CreGFP) severely deficient in Kiss1 expression, were used. It was observed that female Kiss1/Cre/Cre mice showed reduced ovulation and impaired fertility whereas; male Kiss1Cre/Cre mice sired normalsized litters. Thus, it is concluded that females require higher levels of Kiss1 expression for competent reproduction as compared to males which require only 5% of normal Kiss1 expression for normal reproduction. Evidence from mutation for importance of Kiss1 gene: Silveira et al. [3] reported the identification of a KISS1 mutation associated with male CPP (Central precocious puberty). It was found that kisspeptin resistance to in vitro degradation is increased which suggests that kisspeptin bioavailability is enhanced which may cause precocious puberty phenotype. Study was done on the role of KISS1 gene mutation in a boy attaining precocious puberty early at 1 year of age. Kisspeptin amino-acid sequencing revealed that proline in position 74 is very important in maintaining the kisspeptin structure. Mutation of proline at 74 position was noted in the subject. So, it suggests that p.P74S makes kisspeptin stable and less degradable due to which its bioavailability increases and CPP results. Mutations of KISS1 gene may cause GnRH-dependent disorders such as central precocious puberty and isolated hypogonadotropic hypogonadism (IHH). In females attaining CPP before 6yr of age, another mutation p.H90D was identified in the homozygous State. Mutations in KISS1 and KISS1R are not common causes of ICPP in girls. Neurokinin B (NKB) and its receptor, neurokinin-3 receptor (NK3R), (encoded by Tac3 and TacR3 respectively) are considered essential elements for normal reproduction. Navarro et al. [8], performed an experiment...
Keywords: Puberty Onset / Central Precocious Puberty / Kiss1 Expression / Kiss1 Gene / Normal Reproduction / Puberty Early

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

Share this article

Click here to see the statistics on "Perceptions in Reproductive Medicine" .
Back to Top Top