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Amniotic fluid INSL3 measured during the critical time window in human pregnancy relates to cryptorchidism, hypospadias and phthalate load: a large case-control study (2018)
Journal Article
Anand-Ivell, R., Cohen, A., Norgaard-Pedersen, B., Joenssen, B., Bonde, J.-P., Hougaard, D. M., Lindh, C., Toft, G., Lindhard, M., & Ivell, R. (2018). Amniotic fluid INSL3 measured during the critical time window in human pregnancy relates to cryptorchidism, hypospadias and phthalate load: a large case-control study. Frontiers in Physiology, 9, Article 408. https://doi.org/10.3389/fphys.2018.00406

The period of the first to second trimester transition in human pregnancy represents a sensitive window for fetal organogenesis, particularly in regard to the development of the male reproductive system. This is a time of relative analytical inaccess... Read More about Amniotic fluid INSL3 measured during the critical time window in human pregnancy relates to cryptorchidism, hypospadias and phthalate load: a large case-control study.

Theca cell INSL3 and steroids together orchestrate the growing bovine antral follicle (2017)
Journal Article
Dai, Y., Ivell, R., & Anand-Ivell, R. (2017). Theca cell INSL3 and steroids together orchestrate the growing bovine antral follicle. Frontiers in Physiology, 8, https://doi.org/10.3389/fphys.2017.01033

Insulin-like peptide 3 (INSL3) and its specific receptor RXFP2 are both expressed by theca interna cells of the growing antral follicle where they form an essential regulatory element in the production of the steroid precursor androstenedione. Using... Read More about Theca cell INSL3 and steroids together orchestrate the growing bovine antral follicle.

Neohormones in milk (2017)
Journal Article
Ivell, R., & Anand-Ivell, R. (2017). Neohormones in milk. Best Practice and Research: Clinical Endocrinology and Metabolism, 31(4), https://doi.org/10.1016/j.beem.2017.10.005

Neohormone systems evolved specifically to regulate those mammalian traits, such as internal fertilization, pregnancy and lactation, which have proved to be central to the success, environmental independence, and adaptability of mammals as a vertebra... Read More about Neohormones in milk.

Male seminal relaxin contributes to induction of the post-mating cytokine response in the female mouse uterus (2017)
Journal Article
Glynn, D. J., Heng, K., Russell, D. L., Sharkey, D. J., Robertson, S. A., Anand-Ivell, R., & Ivell, R. (2017). Male seminal relaxin contributes to induction of the post-mating cytokine response in the female mouse uterus. Frontiers in Physiology, 8, Article 422. https://doi.org/10.3389/fphys.2017.00422

The hormone relaxin is important in female reproduction for embryo implantation, cardiovascular function, and during labor and lactation. Relaxin is also synthesized in males by organs of the male tract. We hypothesized that relaxin might be one comp... Read More about Male seminal relaxin contributes to induction of the post-mating cytokine response in the female mouse uterus.

Relaxin-family peptide receptors 1 and 2 are fully functional in the bovine (2017)
Journal Article
Dai, Y., Ivell, R., Liu, X., Janowski, D., & Anand-Ivell, R. (2017). Relaxin-family peptide receptors 1 and 2 are fully functional in the bovine. Frontiers in Physiology, 8, Article 359. https://doi.org/10.3389/fphys.2017.00359

In most mammals the peptide hormone relaxin is a key physiological component regulating early pregnancy and birth. However, synteny analysis shows that the gene encoding ovarian relaxin-2 is deleted in cows and sheep. While, these ruminants appear to... Read More about Relaxin-family peptide receptors 1 and 2 are fully functional in the bovine.

Relaxin-like peptides in male reproduction: a human perspective (2017)
Journal Article
Ivell, R., Agoulnik, A. I., & Anand-Ivell, R. (2017). Relaxin-like peptides in male reproduction: a human perspective. British Journal of Pharmacology, 174(10), 990-1001. https://doi.org/10.1111/bph.13689

The relaxin family of peptide hormones and their cognate GPCRs are becoming physiologically well-characterized in the cardiovascular system and particularly in female reproductive processes. Much less is known about the physiology and pharmacology of... Read More about Relaxin-like peptides in male reproduction: a human perspective.

Endocrinology of the Fetal Testis (2017)
Book Chapter
Ivell, R., Anand-Ivell, R., & Morley, S. D. (2017). Endocrinology of the Fetal Testis. In M. Simoni, & I. Huhtaniemi (Eds.), Endocrinology of the Testis and Male Reproduction (245-272). Springer. https://doi.org/10.1007/978-3-319-44441-3_7

The human fetus, already at a very early stage in its development, is hormonally active, with the testis and adrenal gland being major contributors. Following sex determination at around weeks 5–6, the somatic cells of the testis begin to differentia... Read More about Endocrinology of the Fetal Testis.

The male fetal biomarker INSL3 reveals substantial hormone exchange between fetuses in early pig gestation (2016)
Journal Article
Vernunft, A., Ivell, R., Heng, K., & Anand-Ivell, R. (2016). The male fetal biomarker INSL3 reveals substantial hormone exchange between fetuses in early pig gestation. PLoS ONE, 11(3), Article e0152689. https://doi.org/10.1371/journal.pone.0152689

The peptide hormone INSL3 is uniquely produced by the fetal testis to promote the transabdominal phase of testicular descent. Because it is fetal sex specific, and is present in only very low amounts in the maternal circulation, INSL3 acts as an idea... Read More about The male fetal biomarker INSL3 reveals substantial hormone exchange between fetuses in early pig gestation.

Perfluorooctane sulfonate concentrations in amniotic fluid, biomarkers of fetal Leydig cell function, and cryptorchidism and hypospadias in Danish boys (1980–1996) (2015)
Journal Article
Toft, G., Jönsson, B. A., Bonde, J. P., Nørgaard-Pedersen, B., Hougaard, D. M., Cohen, A., Lindh, C. H., Ivell, R., Anand-Ivell, R., & Lindhard, M. S. (2016). Perfluorooctane sulfonate concentrations in amniotic fluid, biomarkers of fetal Leydig cell function, and cryptorchidism and hypospadias in Danish boys (1980–1996). Environmental Health Perspectives, 124(1), 151-156. https://doi.org/10.1289/ehp.1409288

Background: Exposure to perfluorooctane sulfonate (PFOS) may potentially disturb fetal Leydig cell hormone production and male genital development.
Objectives: We aimed to study the associations between levels of amniotic fluid PFOS, fetal steroid h... Read More about Perfluorooctane sulfonate concentrations in amniotic fluid, biomarkers of fetal Leydig cell function, and cryptorchidism and hypospadias in Danish boys (1980–1996).

Longitudinal assessment of circulating insulin-like peptide 3 levels in healthy peripubertal girls (2014)
Journal Article
Hagen, C. P., Mieritz, M. G., Nielsen, J. E., Anand-Ivell, R., Ivell, R., & Juul, A. (2015). Longitudinal assessment of circulating insulin-like peptide 3 levels in healthy peripubertal girls. Fertility and Sterility, 103(3), https://doi.org/10.1016/j.fertnstert.2014.11.014

Objective: To elucidate the natural course of circulating insulin-like peptide 3 (INSL3) levels according to puberty as well as its relation to other reproductive hormones.
Design: Population-based cohort study.
Setting: Not applicable.
Patient(s)... Read More about Longitudinal assessment of circulating insulin-like peptide 3 levels in healthy peripubertal girls.

Amniotic fluid phthalate levels and male fetal gonad function (2014)
Journal Article
Jensen, M. S., Anand-Ivell, R., Nørgaard-Pedersen, B., Jönsson, B. A., Bonde, J. P., Hougaard, D. M., Cohen, A., Lindh, C. H., Ivell, R., & Toft, G. (2015). Amniotic fluid phthalate levels and male fetal gonad function. Epidemiology, 26(1), 91-99. https://doi.org/10.1097/EDE.0000000000000198

Background: Prenatal exposure to phthalates may pose a threat to human male reproduction. However, additional knowledge about the in vivo effect in humans is needed, and reported associations with genital abnormalities are inconclusive. We aimed to s... Read More about Amniotic fluid phthalate levels and male fetal gonad function.

Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling (2014)
Journal Article
Barthold, J. S., Robbins, A., Wang, Y., Pugarelli, J., Mateson, A., ANAND-IVELL, R., Ivell, R., McCahan, S. M., & Akins, R. E. (2014). Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling. Biology of Reproduction, 91(2), Article 41. https://doi.org/10.1095/biolreprod.114.119560

Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling (2014)
Journal Article
Barthold, J. S., Robbins, A., Wang, Y., Pugarelli, J., Mateson, A., Anand-Ivell, R., Ivell, R., McCahan, S. M., & Akins, R. E. J. (2014). Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling. Biology of Reproduction, 91(2), https://doi.org/10.1095/biolreprod.114.119560

Cryptorchidism, or undescended testis, is a common male genital anomaly of unclear etiology. Hormonal stimulation of the developing fetal gubernaculum by testicular androgens and insulin-like 3 (INSL3) is required for testicular descent. In studies o... Read More about Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling.

Insulin-like factor 3 and the HPG axis in the male (2014)
Journal Article
Ivell, R., Heng, K., & Anand-Ivell, R. (in press). Insulin-like factor 3 and the HPG axis in the male. Frontiers in Endocrinology, 5(6), https://doi.org/10.3389/fendo.2014.00006

The hypothalamic–pituitary–gonadal (HPG) axis comprises pulsatile GnRH from the hypothalamus impacting on the anterior pituitary to induce expression and release of both LH and FSH into the circulation. These in turn stimulate receptors on testicular... Read More about Insulin-like factor 3 and the HPG axis in the male.

Serum levels of insulin-like factor 3, anti-Müllerian hormone, inhibin B, and testosterone during pubertal transition in healthy boys: a longitudinal pilot study (2014)
Journal Article
Johansen, M. L., Anand-Ivell, R., Mouritsen, A., Hagen, C. P., Mieritz, M. G., Søeborg, T., Johannsen, T. H., Main, K. M., Andersson, A.-M., Ivell, R., & Juul, A. (2014). Serum levels of insulin-like factor 3, anti-Müllerian hormone, inhibin B, and testosterone during pubertal transition in healthy boys: a longitudinal pilot study. Reproduction, 147, https://doi.org/10.1530/REP-13-0435

Insulin-like factor 3 (INSL3) is a promising marker of Leydig cell function with potentially high clinical relevance. Limited data of INSL3 levels in relation to other reproductive hormones in healthy pubertal boys exist. In this study, we aimed to e... Read More about Serum levels of insulin-like factor 3, anti-Müllerian hormone, inhibin B, and testosterone during pubertal transition in healthy boys: a longitudinal pilot study.

Human Testicular Insulin-Like Factor 3 and Endocrine Disrupters (2014)
Book Chapter
Bay, K., & Anand-Ivell, R. (2014). Human Testicular Insulin-Like Factor 3 and Endocrine Disrupters. In Endocrine Disrupters (327-348). Elsevier. https://doi.org/10.1016/B978-0-12-800095-3.00012-2

The hormone insulin-like factor 3 (INSL3) is produced by testicular Leydig cells. Production of INSL3 is dependent on the state of Leydig cell differentiation and is stimulated by the long-term trophic effects of luteinizing hormone. INSL3 is, along... Read More about Human Testicular Insulin-Like Factor 3 and Endocrine Disrupters.

Insulin-like factor 3 as a monitor of endocrine disruption (2013)
Journal Article
Anand-Ivell, R., & Ivell, R. (2014). Insulin-like factor 3 as a monitor of endocrine disruption. Reproduction, 147, Article R87-R95. https://doi.org/10.1530/REP-13-0486

Insulin-like factor 3 (INSL3) is generated and secreted by differentiated interstitial Leydig cells of the testes in both fetal and adult males of all mammalian species so far analyzed. All evidence to date suggests that it is produced constitutively... Read More about Insulin-like factor 3 as a monitor of endocrine disruption.

Circulating insulin-like factor 3 (INSL3) in healthy and infertile women (2013)
Journal Article
Anand-Ivell, R., Tremellen, K., Dai, Y., Heng, K., Yosida, M., Knight, P., & Ivell, R. (2013). Circulating insulin-like factor 3 (INSL3) in healthy and infertile women. Human Reproduction, 28(11), https://doi.org/10.1093/humrep/det3

Study question: How does insulin-like factor 3 (INSL3) concentration in blood vary across the menstrual cycle in women?
Summary answer: INSL3 is secreted by the theca interna cells of growing antral follicles and is phasic in its expression.
What i... Read More about Circulating insulin-like factor 3 (INSL3) in healthy and infertile women.

Circulating insulin-like factor 3 (INSL3) in healthy and infertile women (2013)
Journal Article
Anand-Ivell, R., Tremellen, K., Dai, Y., Heng, K., Yoshida, M., Knight, P. G., Hale, G. E., & Ivell, R. (2013). Circulating insulin-like factor 3 (INSL3) in healthy and infertile women. Human Reproduction, 28(11), 3093-3102. https://doi.org/10.1093/humrep/det349

STUDY QUESTIONHow does insulin-like factor 3 (INSL3) concentration in blood vary across the menstrual cycle in women?SUMMARY ANSWERINSL3 is secreted by the theca interna cells of growing antral follicles and is phasic in its expression.WHAT IS KNOWN... Read More about Circulating insulin-like factor 3 (INSL3) in healthy and infertile women.