The leucine-rich repeat-containing G protein-coupled receptor 8 gene T222P mutation does not cause cryptorchidism.

CONTEXT: Insulin-like 3 and its receptor, leucine-rich repeat-containing G protein-coupled receptor 8 (LGR8), are essential for the first phase of testicular descent. Homozygous loss of either of the two genes in mice leads to cryptorchidism. Although mutations in both homologous human genes are not a common cause of cryptorchidism. To date, only one missense mutation at codon 222 (T222P) of the LGR8 gene has been proposed as a causative mutation for cryptorchidism. This conclusion was based on both functional in vitro studies and the lack of mutation in a large group of controls. The geographical origin of the mutation carriers suggested a founder effect in the Mediterranean area. OBJECTIVES: We sought to define the frequency of the T222P mutation in four different countries to assess whether the screening for this mutation could be of use as a diagnostic genetic test. MATERIALS AND METHODS: A total of 822 subjects (359 with a history of cryptorchidism and 463 controls) from Italy, Spain, Hungary, and Egypt were genotyped for the T222P mutation by direct sequencing. RESULTS: The phenotypical expression of the mutation also included normal testicular descent. The mutation frequency was not significantly different in cryptorchid patients vs. noncryptorchid controls (3.6 vs. 1.7%, respectively). No significant geographical differences were observed in mutation frequencies. The haplotype analysis allowed us to predict three distinct haplotypes, i.e. three possible mutation events. CONCLUSIONS: Our results suggest that the T222P mutation cannot be considered either causative or a susceptibility factor for cryptorchidism. A true causative mutation in the LGR8 gene still remains to be identified.

Bone, blood and semen lead in men with environmental and moderate occupational exposure.

Lead (Pb) in blood, bone, and semen was measured in 162 to 186 environmentally exposed men from Mexico City, aged 19- 48. Semen Pb was measured by inductively coupled plasma mass spectrometry, blood Pb by atomic absorption spectrometry and bone Pb by K X-ray fluorescence. Mean Pb levels in blood, semen, tibia (cortical) and patella (trabecular) bone were 12 microg/dl, 2.7 microg/l, 13 microg/g, and 20 microg/g, respectively. Semen Pb was determined by blood Pb and patella Pb. Determinants of higher tibia Pb were age, living near industry in which Pb is used, and a high occupational Pb exposure index. Higher patella Pb was predicted by age, higher traffic density near home, a high index of occupational exposure to Pb and a greater number of cigarettes smoked per day in the year prior to the study. Blood and bone Pb results are consistent with findings in other populations. Semen results provide new information on the semen-bone Pb relationship. Bone, especially trabecular one, proved to be a significant endogenous lead source for blood and semen burdens in reproductive aged men.