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Luteal insufficiency is characterized by a premature decrease of serum progesterone concentration and pregnancy loss during the luteal phase. Hypoluteoidism is discussed as a possible cause of pregnancy loss in dogs that resorb, abort, or whelp prematurely without visible infectious or non-infectious abnormalities of the pregnancy. Luteal insufficiency in the bitch usually first occurs during the second pregnancy and is accompanied by individual shortening of the estrous cycle and unnoticed resorption within the early stage of gestation. The reasons for hypoluteoidism still remained unclear.
Interestingly, antibodies against progesterone and estrogen were found in the sera of women with autoimmune progesterone dermatitis and lymphocytes could be found in the corpora lutea of different species.
The aim of this study was to investigate the concentration of progesterone, prolactin, and relaxin in hypoluteoid bitches and control animals in the early luteal phase in pregnancy and the nonpregnant-cycle. Moreover, canine antibodies against progesterone were analyzed regarding a possible connection between embryonic loss associated with hormone changes related to a hormone antibody response. A new enzyme-linked immunosorbent assay (ELISA) was developed and optimized in this regard. Serum samples from 20 short-cycling bitches and 18 control animals were examined particularly in regard to the prevalence of IgE and IgM against progesterone. As another part of this investigation, tissue samples from the corpora lutea of four luteal insufficient and two control animals were collected during ovariohysterectomy. The expression of selected parameters of the prostaglandin system and accordingly immunological cell surface molecules was assessed by Real Time PCR.
The results show that the progesterone decline was not associated with a lack of the luteotropic hormones prolactin and relaxin. The expression of the parameters from the prostaglandin system did not differ between the luteal insufficient and control group. Moreover, a possible influence of the immune system on the disturbed luteal function could be demonstrated in this study. Antibodies against progesterone could be detected in the sera of bitches for the first time. The analysis of IgE seems to be most suitable to detect canine anti-progesterone antibodies in connection with luteal insufficiency. Furthermore, the expression of CD25 mRNA could be detected also in the canine ovary and may indicate the presence of regulatory T-cells in the corpus luteum. The analysis of the additional immunological cell surface molecules showed a high expression of CD3, CD4, CD8 and CD25 in the bitch with IgE antibodies against progesterone. A higher expression of CD25 in all luteal insufficient bitches could be observed as a general tendency in comparison to the control animals.
The presented data show that neither a disturbed secretion of luteotrophic hormones nor a dysfunction in gene expression of the prostaglandin system were causally related to luteal insufficiency of the examined bitches. However, an autoreactive process could be identified in connection with hypoluteoidism for the first time. This preliminary research may act as a base for optimized assay systems to detect autoimmune reaction in connection with fertility problems and could lead to a reduction in diagnostic errors.