Childlessness - Infertility - TEX 13 B

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తల్లి శపిస్తే పిల్లలు పుట్టరని చెప్పుకునేవారు. ఇప్పుడు దాన్నే CCMB  Testis-Expressed Protein 13Bతో శాస్త్రీయంగా వివరించింది.

TEX 13 B

childlessness

Childlessness is the state of not having children. Childlessness may have personal, social or political significance.

Childlessness, which may be by choice or circumstance, is distinguished from voluntary childlessness, also called being "childfree", which is voluntarily having no children, and from antinatalism, wherein childlessness is promoted.

Types

See also: Clerical celibacy

Types of childlessness can be classified into several categories:[1]

natural sterility randomly affects individuals. One can think of it as the minimum level of permanent childlessness that we can observe in any given society, and is of the order of 2 percent, in line with data from the Hutterites, a group established as the demographic standard in the 1950s.

social sterility, which one can also call poverty-driven childlessness, or endogenous sterility, describes the situation of poor women whose fecundity has been affected by poor living conditions.

people who are childless by circumstance. These people can be childless because they have not met a partner with whom they would like to have children, or because they tried unsuccessfully to conceive at an advanced maternal age, or because they suffer from certain medical issues, such as endometriosis or polycystic ovary syndrome (PCOS), that make it difficult for them to conceive.

people who are childless by choice.

The first three categories are often grouped under the label "involuntary childlessness". The latter category is often called "voluntary childlessness", also described as being "childfree", occurring when one decides not to reproduce.

TEX13B is important for germ cell development and male fertility

Umesh Kumar, Digumarthi V S Sudhakar, Nithyapriya Kumar, Hanuman T Kale, Rajan Kumar Jha, Nalini J Gupta, B N Chakravarthy, Mamata Deenadayal, Aarti Deenadayal Tolani,  View ORCID ProfileSwasti Raychaudhuri, P Chandra Shekar, Kumarasamy Thangaraj

doi: https://doi.org/10.1101/2022.01.11.475851

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AbstractFull TextInfo/HistoryMetrics Preview PDF

Abstract

The recent epidemiological studies suggest that nearly one out of every 7 reproductive age couples face problem to conceive a child after trying for at least one year. Impaired fertility of the male partner is causative in approximately 50% of the infertile couples. However, the etiologies of large proportion of male infertility are still unclear. Our unpublished exome sequencing data identified several novel genes including TEX13B, which motivated us to further explore the role of TEX13B in male infertility in large infertile case control cohort. Hence in this study, we have examined the role of TEX13B in male infertility by whole gene sequencing 628 infertile and 427 control men and have demonstrated the functional role of Tex13b in spermatogonia GC1spg (GC1) cells. We identified 2 variants on TEX13B which are tightly associated with male infertility. TEX13B gene exclusively expressed in germ cells, but its molecular functions in germ cells are still unknown. Hence, we demonstrated the functional importance of Tex13b in GC1 cell line by genomic manipulation via CRISPR-Cas9 and mass spectrometry-based whole cell proteomics. The gene knock out in GC1 cell line clearly shows that Tex13b play an important role in germ cell growth and morphology. We demonstrate that Tex13b knockout or conditional overexpression in GC1 cells reprograms the metabolic status from an oxidative phosphorylation to glycolysis state and vice versa. In conclusion, our study clearly showed the importance of Tex13b in germ cells development and Its association with male infertility.

Introduction

Infertility, defined as inability of a couple to conceive a child after trying to conceive for one year is a major reproductive health problem in about 15 percent reproductive age couples around the globe (ref). Impaired fertility of the male partner is causative risk factor in approximately 50% of the infertile couples. Data from our laboratory has shown that about 8.5% infertility among Indian men is due to the Y chromosome microdeletion. Further, analysis of several autosomal genes (CAMK4, UBE2B and TNP2-4) accounted for additional 17.5% genetic factors responsible for infertility among Indian men (ref). However, etiologies of large proportion of male infertility are still unclear therefore, it is essential to identify the novel causative mutations for male infertility.

Recent genomic studies revealed that the mutations in mammalian X chromosome have direct impact on fertility because X chromosome is enriched for genes involved in spermatogenesis (Stouffs et al., 2009). A recent study has shown that an x chromosome gene TEX11 mutations were a common cause of meiotic arrest and azoospermia in infertile men (Yang et al., 2015). Another study has stress on the X chromosome genes which express exclusively male germ cells, identified 10 X-linked genes, including Tex13b in mouse as well as human homolog of Tex13, TEX13B. TEX13B is orthologous to mouse gene Tex13b that is found to be is involved in transcriptional regulation during spermatogenesis (Wang et al., 2001). Furthermore, recently it has been shown that Tex13b express specifically pre-leptotene stage of the spermatogonia cells, indicating its potent role in spermatogenesis. The importance of Tex13b in spermatogonia differentiation is indicated in another study since Tex13b found to be most highly connected to the genes specific to germ cells by hub-gene-network analysis (Liao et al., 2017). However, the molecular function TEX13B gene is yet to be explored in germ cells and its association in male infertility.

Since TEX13B has been found as a novel hit in our exome sequencing (unpublished), we have sequenced the coding region (exon 2 and 3) of TEX13B in 628 infertile men (nature of infertile patients) along with 427 ethnically matched fertile controls. We have identified two variants in the coding region of TEX13B and found to be significantly associated with azoospermia patients. To explore the molecular function of TEX13B we created the Tex13b knockout spermatogonia GC1spg (GC1) cells. We specifically choose GC1 cells to characterized Tex13b because these cells belong to pre-leptotene stage of germ cells (spermatogonia B) and Tex13 expresses specifically at this stage (Hofmann, Narisawa, Hess, & Millan, 1992; Wang et al., 2001). Since Tex13b shown to be a transcription factor, hence, to examine the differential protein expression in Tex13b knockout cells we performed isotope labeling by amino acid in cell culture (SILAC) and mass spectrometry-based proteomics. Results in this study clearly show that Tex13b regulate balance between OXPHOS and glycolysis.

Results

TEX13B variants associated with male infertility

TEX13B (Testis-Expressed Protein 13B) is another candidate gene identified by exome sequencing with the non-synonymous variant rs41300872 (p.Gly197Arg) showing significant association with male infertility (OR=1.77, 95% CI); P=0.002. TEX13B is a gene located on X-chromosome and is exclusively expressed in male germ cells and spermatogonia (Wang, McCarrey, Yang, & Page, 2001). To identify additional genetic variants, we sequenced the complete coding region of TEX13B in 628 infertile men (443 NOA, 105 OAT and 80 severe oligozoospermia individuals) along with 427 ethnically matched fertile control men (Table 1). We found an additional rare variant, rs775429506 (p.Gly237Glu) exclusively in two NOA men.

Is infertility genetic in males?

Male-factor infertility and genetics: Is male infertility ...

Some experts estimate that 10–15% of male infertility cases are caused by genetics — others calculate it's more like 60%. So while other male fertility factors like age, diet, lifestyle, and hormones may be common, genetics is sometimes a factor or even the sole cause of male-factor infertility.2 Aug 2022