The longstanding focus of the Richburg laboratory is to decipher the molecular and cellular mechanisms by which exposure to certain environmental (e.g., phthalate acid ester-based plasticizers) or clinical chemotherapeutic agents (e.g., cisplatin) can result in disruption of male reproduction. Specifically, the unifying theme of the research conducted in my laboratory is targeted at understanding the paracrine cellular signaling mechanisms between the Sertoli cells and germ cells in the testis that regulate the death (and/or survival) of germ cells by the process of apoptosis. Recent experimental findings in my laboratory have implicated the cells of the innate immune system in the exacerbation of phthalate-induced injury to the testis. Interestingly, the infiltration of these immune cells may account, in part, for the long recognized differences in the age- and species-dependent sensitivity to MEHP-induced testicular injury and germ cell loss. The inappropriate loss of testicular germ cells via apoptosis during various developmental periods of life could ultimately lead to clinical male infertility in adulthood. It is anticipated that the mechanistic insights garnered from our research will be useful for predicting and preventing human reproductive health risks to chemicals found in the environment.

Age- and species-dependent infiltration of macrophages into the testis of rats and mice exposed to mono-(2-ethylyhexyl) phthalate (MEHP). Biology of Reproduction. (2014) 91(1):18, 1-11. PMID:24876407

 The role of E3 ligases in the ubiquitin-dependent regulation of spermatogenesis. (2014) Seminars in Cell and Developmental Biology 30: 27-35. PMID:24632385[PubMed - as supplied by publisher]

Characterization of the role of tumor necrosis factor apoptosis inducing ligand (TRAIL) in spermatogenesis through the evaluation of Trail gene-deficient mice. (2014) PLoS One. 2014 Apr 15;9(4):e93926. doi: 10.1371/journal.pone.0093926. eCollection 2014. PMID:24736722

Cisplatin-induced alterations in the functional stem cell pool and niche in C57BL/6J mice following a clinically relevant multi-cycle exposure. (2014) Toxicology Letters Apr 2;227(2):99-112. doi: 10.1016/j.toxlet.2014.03.019. [Epub ahead of print] PMID:24704392 [PubMed - in process]

Age-dependent alterations in spermatogenesis in itchy mice. (2012) Spermatogenesis 2(2), 104-116.

Mono-(2-ethylhexyl) phthalate (MEHP) promotes invasion and migration of human testicular embryonal carcinoma cells. (2012) Biology of Reproduction 86(5), 160, 1-10.

Transcriptional suppression of Sertoli cell Timp2 in rodents following mono-(2-ethylhexyl) phthalate exposure is regulated by CEBPA and MYC. (2011) Biology of Reproduction 85(6), 1203-15.

FasL gene-deficient mice display a limited disruption in spermatogenesis and inhibition of mono-(2-ethylhexyl) phthalate-induced germ cell apoptosis (2010) Toxicological Sciences 114, 335-345.

MEHP-induced disruption of junctional complexes in the seminiferous epithelium of the rodent testis is mediated by MMP2 (2010) Biology of Reproduction 82, 516-527.

TNF alpha-mediated disruption of spermatogenesis in response to Sertoli cell injury in rodents is partially regulated by MMP2. (2009) Biology of Reproduction 80, 581-9.

Dwyer, J, and Richburg, JH (2012). Age-dependent roles of ITCH during mouse testicular development. Annual Meeting of the Society of Toxicology, March 11-15, 2012; San Francisco, CA.

Lin, Y, and Richburg, JH (2012). FasL regulates testicular germ cell c-FLIP levels through gene expression and ubiquitination. Annual Meeting of the Society of Toxicology, March 11-15, 2012; San Francisco, CA.

Harman, J and Richburg, JH (2012). Deciphering mechanisms underlying prolonged male infertility following a clinically-relevant multi-cycle cisplatin treatment. Annual Meeting of the Society of Toxicology, March 11-15, 2012; San Francisco, CA.

Lin, Y, and Richburg, JH (2013). Deciphering the role of TRAIL in altering spermatogenesis by controlling germ cell apoptosis. Annual Meeting of the Society of Toxicology, March 10-14, 2013; San Antonio, TX.

Harman, J and Richburg, JH (2013). Impact of clinically relevant cisplatin treatment on the undifferentiated spermatogonia population and niche. Annual Meeting of the Society of Toxicology, March 10-14, 2013; San Antonio, TX.

Lin, Y, and Richburg, JH (2013). Characterization of the role of tumor necrosis factor apoptosis inducing ligand (TRAIL) in spermatogenesis through the evaluation of TRAIL gene-deficient mice. Annual Meeting of the Society of Andrology/Testis Workshop, April 10-13, 2013; San Antonio, TX.

Murphy, C, Stermer, A and Richburg, JH (2013). Neutrophil and macrophage infiltration precedes germ cell apoptosis after mono-(2-ethylhexyl) phthalate exposure in an age- and species-dependent manner. Annual Meeting of the Society of Andrology/Testis Workshop, April 10-13, 2013; San Antonio, TX.

Murphy, CJ, Stermer, AR, and Richburg, JH (2013). Age- and species-dependent macrophage infiltration into the testis after mono-(2-ethylhexyl) phthalate exposure. Gordon Research Conference: Molecular and Cellular Mechanisms of Toxicity, August 7-12, 2013; Proctor Academy, Andover, NH.

Murphy, CJ, Stermer, AR, and Richburg, JH (2014). Age-dependent macrophage infiltration into the testis of rats and mice after mono-(2-ethylhexyl) phthalate (MEHP). 53^rd Annual Meeting of the Society of Toxicology, March 26, 2014; Phoenix, AZ.

Stermer, AR, Murphy, CJ, and Richburg, JH (2014). Differential infiltration of macrophages into the testis after mono (2-ethylhexyl) phthalate exposure in F344 rats and C57B6/J mice. 53^rd Annual Meeting of the Society of Toxicology, March 26, 2014; Phoenix, AZ.

Murphy, CJ, Stermer, AR, and Richburg, JH (2014). Age, dose, and species-dependent macrophage infiltration into the testis of rats after mono-(2-ethylhexyl) phthalate (MEHP) exposure. 47^th Annual Meeting of the Society for the Study of Reproduction, July 19-23, 2014; Grand Rapids, MI.

Murphy C, Kumar L, Chou J, Perez CJ, Jeter CR, Otto NW, De La Torre S, Jaubert J, Guénet J-L, Geha RS, Richburg JH, Dent SY, Benavides F (2014). The spontaneous mouse mutation ébouriffé (ebo), associated with postnatal lethality, infertility and wavy hair, is a nonsense allele of the Lrrc8a (Swell1) gene. The 28^th International Mammalian Genome Conference, October 26-29, 2014; Bar Harbor, ME.

Murphy, CJ, Stermer, AR, and Richburg, JH (2015). Mono-(2-ethylhexyl) phthalate-induced Sertoli cell injury stimulates macrophage infiltration and the production of pro-inflammatory cytokines in peripubertal male Fischer rats. 54^th Annual Meeting of the Society of Toxicology, March 22-26, 2015; San Diego, CA.

Stermer, AR, Murphy, CJ and Richburg, JH (2015). Acute mono-2-ethylhexyl phthalate exposure causes time-dependent alteration in macrophage functionality in the peripubertal Fischer rat testis. 54^th Annual Meeting of the Society of Toxicology, March 22-26, 2015; San Diego, CA.

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