Delineating the regulation of estrogen and androgen receptor expression by sex steroids during rat spermatogenesis.

Estrogen receptors (ERα and β) and androgen receptor (AR) regulate various critical processes during spermatogenesis. Since spermatogenesis is very sensitive to hormonal stimuli and perturbations, it is important to understand the regulation of expression of these receptors by sex steroid hormones. Although many studies have reported deregulation of steroid receptors on endocrine disruption, there is no consensus on the regulation of their expression by steroid hormones during spermatogenesis, and a lack of clear understanding of the mechanism of regulation.

Estrogen, through estrogen receptor 1, regulates histone modifications and chromatin remodeling during spermatogenesis in adult rats.

Estrogen receptors (ESR1 and ESR2) play crucial roles in various processes during spermatogenesis. To elucidate individual roles of ESRs in male fertility, we developed in vivo selective ESR agonist administration models. Adult male rats treated with ESR1 and ESR2 agonist for 60 days show spermatogenic defects leading to reduced sperm counts and fertility.

Estrogen signaling, through estrogen receptor β, regulates DNA methylation and its machinery in male germ line in adult rats.

Estrogen, through its receptors, regulates various aspects of spermatogenesis and male fertility. To understand the roles of estrogen receptors (ERα and ERβ) in male fertility, we have developed in vivo selective ER agonist administration models. Treatment of adult male rats with ERα or ERβ agonist for 60 d decreases fertility and litter size mainly due to increased pre- and post-implantation embryo loss.

Direct regulation of genes involved in sperm release by estrogen and androgen through their receptors and coregulators.

Steroid hormones, estrogen and androgen, control transcription in various reproductive and non-reproductive tissues. Both hormones are known to be important for control of sperm release from the seminiferous epithelium (spermiation), a process characterized by extensive remodeling of actin filaments and endocytosis. Earlier studies with an estrogen (E2)-induced rat model of spermiation failure revealed genes involved in actin remodeling (Arpc1b and Evl) and endocytosis (Picalm, Eea1, and Stx5a) to be differentially regulated.

Actin related protein complex subunit 1b controls sperm release, barrier integrity and cell division during adult rat spermatogenesis.

Actin remodeling is a vital process for signaling, movement and survival in all cells. In the testes, extensive actin reorganization occurs at spermatid-Sertoli cell junctions during sperm release (spermiation) and at inter Sertoli cell junctions during restructuring of the blood testis barrier (BTB). During spermiation, tubulobulbar complexes (TBCs), rich in branched actin networks, ensure recycling of spermatid-Sertoli cell junctional molecules.

Differential roles of estrogen receptors, ESR1 and ESR2, in adult rat spermatogenesis.

Estrogens, through their receptors, play an important role in regulation of spermatogenesis. However, the precise role of the estrogen receptors (ESR1 and ESR2) has been difficult to determine as in vivo estradiol treatment would signal through both the ESRs. Hence we had developed in vivo selective ESR agonist administration models in adult male rats to decipher the individual roles of the ESRs.

Effect of estrogen receptor-subtype-specific ligands on fertility in adult male rats.

Maintenance of normal male fertility relies on the process of spermatogenesis which is under complex endocrine control by mechanisms involving gonadotropin and steroid hormones. Although testosterone is the primary sex steroid in males, estrogen is locally produced in the testis and plays a very crucial role in male fertility. This is evident from presence of both the estrogen receptors alpha (ERα) and beta (ERβ) in the testis and their absence, as in the case of knockout mice models, leads to sterility.

Estrogen and androgen regulate actin-remodeling and endocytosis-related genes during rat spermiation.

Spermiation, the sperm release process, is imperative to male fertility and reproduction. Morphologically, it is characterized by removal of atypical adherens junctions called ectoplasmic specializations, and formation of transient endocytic devices called tubulobulbar complexes requiring cytoskeleton remodeling and recruitment of proteins needed for endocytosis. Earlier, estrogen administration to adult male rats was seen to cause spermiation failure due to disruption of tubulobulbar complexes.

Aberrant methylation of multiple imprinted genes in embryos of tamoxifen-treated male rats.

Genomic imprinting is an epigenetic phenomenon known to regulate fetal growth and development. Studies from our laboratory have demonstrated that treatment of adult male rats with tamoxifen increased postimplantation loss around mid gestation. Further studies demonstrated the aberrant expression of transcripts of several imprinted genes in the resorbing embryos at days 11 and 13 of gestation including IGF2.

Proteomics in reproductive biology: beacon for unraveling the molecular complexities.

Proteomics, an interface of rapidly evolving advances in physics and biology, is rapidly developing and expanding its potential applications to molecular and cellular biology. Application of proteomics tools has contributed towards identification of relevant protein biomarkers that can potentially change the strategies for early diagnosis and treatment of several diseases. The emergence of powerful mass spectrometry-based proteomics technique has added a new dimension to the field of medical research in liver, heart diseases and certain forms of cancer.