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Apr 28, 2014

Study of Seipin Protein Clarifies Role of Body Fat in Male Infertility

  • Aware that obesity impairs male fertility, scientists based in China were curious to explore whether too little body fat, as opposed to too much, also compromises male reproduction. These scientists, who were based at Nanjing Medical University, hoped that they would be able to move beyond the vague associations that could be gleaned from the single relevant meta-analysis available to them. According to this study, a low body mass index was associated with an increased but nonsignificant risk of abnormal sperm count.

    The researchers began by sifting through the conflicting information available from studies of congenital generalized lipodystrophy (CGL), which is also known as Berardinelli-Seip congential lipodystrophy. This condition, which is characterized by a lack of subcutaneous body fat, is caused by mutations in BSCL2-encoding seipin.

    While at least one study mentioned that men with CGL were fertile, it did not present specific data. However, when the researchers at Nanjing Medical University investigated the subject themselves, they made the surprising discovery that seipin-deficient mice not only model BSCL2 with marked lipodystrophy but also exhibit complete male infertility.

    Intrigued—and determined to evaluate a link between lipodystrophy and male fertility—the researchers decided to examine reproductive function and sperm quality in male CGL type 2/BSCL2 patients. In addition, they began characterizing mice with adipose- and germ cell-specific lack of seipin. The researchers detailed these initiatives April 28 in the Proceedings of the National Academy of Sciences, in an article entitled “Lack of testicular seipin causes teratozoospermia syndrome in men.”

    Seipin, the authors noted, is a transmembrane protein localizing to the endoplasmic reticulum that is highly expressed in human brain, testis, and adipose tissue. Previously, lack of seipin in the brain had been linked to motor neuropathy and Silver syndrome, and loss in adipose tissue had been linked with severe lipodystrophy. But the researchers were interested in clarifying its role in testis.

    In their article, the authors reported on teratozoospermia syndrome in a lipodystrophic patient with compound BSCL2 mutations. This patient, the authors observed, had sperm defects resembling the defects of infertile seipin null mutant mice. “Human patients and mouse models lacking seipin in germ cells produce severely abnormal sperm because of impaired lipid distribution during sperm maturation,” they wrote.

    The authors detailed their specific results as follows: Spermatids of the human patient and mice devoid of seipin in germ cells are morphologically abnormal with large ectopic lipid droplets and aggregate in dysfunctional clusters. Elevated levels of phospatidic acid accompanied with an altered ration of polyunsaturated to monounsaturated and saturated fatty acids in mutant mouse testes indicate impaired phospholipid homeostasis during spermiogenesis.”

    The authors concluded that testicular but not adipose tissue-derived sepin is essential for male fertility by modulating testicular phospholipid homeostasis: “These defects are testis-intrinsic; scarcity of adipose tissue per se does not affect male fertility.”


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